ABSTRACT
Background The pandemic has accelerated the introduction of more flexible and cost-effective treatment forms. The efficacy of trastuzumab in the intravenous (IV) and SC forms is similar both in early and advanced HER2-positive breast cancer (BC) patients. Compared to IV administration, SC enables reduction of treatment costs and time, and saves equipment and human resources. SC formulation is more convenient for both patients and healthcare providers and may be implemented as a home-based therapy. Recently, systemic anticancer treatment (including chemotherapy) has been increasingly performed at home, improving patient comfort and reducing the burden on the healthcare system. Poland has already implemented home-based treatment with some biologic compounds;however, they have not included trastuzumab in BC patients. Objectives This RWE analysis aims to evaluate the organizational and therapeutic procedures related to the home-based treatment with SC trastuzumab and the attitudes of patients and healthcare providers to this approach. Material and methods The study enrolled early HER2(+) BC patients treated with trastuzumab during the COVID-19 pandemic. Monitoring and treatment duration were consistent with SmPC and reimbursement regulations in Poland. The first 3-6 doses of SC trastuzumab (alone or in combination with CHT) were administered at a cancer center in outpatient and inpatient settings. Subsequent doses were administered at home by 3 qualified breast nurses. Post-injection follow-up was used for educational purposes. Data were analyzed with descriptive statistics. The study was reviewed and approved by the local Bioethics Committee. Results The analysis included 20 patients treated in two comprehensive cancer centers in Poland with a median age of 59 years (range, 36-72 years). Seven patients (35%) were professionally active. The average distance from the place of residence to the cancer center was 24 km (range, 2-65 km). A total of 232 doses were administered (mean 11.6 doses per patient;range 6-14), 133 doses at home and 99 at the cancer center. The overall tolerance of trastuzumab was good and consistent with the known safety profile described in Summary of Product Characteristics. Only 1 patient (5%) discontinued treatment prematurely due to decreased LVEF;another 19 patients completed treatment as planned. For 19 patients (95%), the benefits of SC treatment included time savings, the ability to continue working, and avoiding crowded places and infection risk. 2 patients (10%) considered the nurse's visit privacy disturbing, while 18 (90%) would recommend home-based drug administration. The average duration of a nurse's stay at home was 60 minutes (range 30 to 130 minutes). No logistical or technical problems were reported, except for occasional patient lateness. Nurses positively assessed the treatment provided in the nursing office, which was a source of additional knowledge, and experience. The overall impression of home-based therapy was positive for both patients and nurses. The limitation of the study is the declarative nature of the data. Conclusions Home-based treatment with SC trastuzumab should be pursued due to its safety, ease of organization, positive perception by patients and nurses, and reducing healthcare system resources. It can be particularly valuable for disabled patients who have difficulty reaching the hospital and professionally active patients. Specialized, trained nurses can self-sufficiently carry out part of the prolonged trastuzumab treatment, reducing physician involvement.
ABSTRACT
Background: HER2+ mBC remains incurable, with a need for new HER2-directed therapies and regimens, including chemotherapy-free options. Zanidatamab (zani) is a novel HER2-targeted bispecific antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of antitumor activity, including complement-dependent cytotoxicity. A CDK4/6 inhibitor combined with endocrine therapy is an approved treatment for HER2-negative/HR+ mBC and this combination has also demonstrated encouraging antitumor activity when paired with HER2-targeted therapy(ies) in HER2+/HR+ mBC. Here, we report results from ZWI-ZW25-202 (NCT04224272), an ongoing singlearm phase 2 study of zani combined with palbociclib (palbo) and fulvestrant (fulv) in pts with HER2+/HR+ mBC. Method(s): Eligibility requirements include: HER2+/HR+ unresectable, locally advanced BC or mBC;ECOG PS of 0 or 1;prior treatment with trastuzumab, pertuzumab and T DM1 (additional prior HER2-targeting agents are permitted);and no prior treatment with CDK4/6 inhibitors. Part 1 of the study evaluated the safety and tolerability of the zani/palbo/fulv combination and determined the recommended doses for use in Part 2, where the antitumor activity of the combination is being evaluated. Endpoints include safety outcomes, progression-free survival at 6 months (PFS6), confirmed objective response rate (cORR) per RECIST v1.1;disease control rate (DCR=complete response [CR] plus partial response [PR] plus stable disease [SD]);duration of response (DOR);PFS;and overall survival. Result(s): As of 24 Feb 2022, 34 pts (33 HER2+/HR+ per central analysis) with a median age of 52 (range 36-77) have been treated. In the metastatic setting, pts had received a median (range) of 4 (1-10) prior systemic regimens, including 3 (1-8) different prior HER2 targeted therapies, and 1 (0-4) endocrine therapy. Seven pts (20%) had prior T DXd treatment and 7 pts had prior fulv treatment. All pts received zani (20 mg/kg Q2W) and standard doses of palbo and fulv. Eighteen pts (53%) remained on treatment;median duration of zani treatment was 6.9 mo (range 0.5- 16.3). A dose-limiting toxicity (DLT) of neutropenia occurred in 1 of 7 DLT-evaluable pts in Part 1. Among all pts (n=34), the most common (>20%) treatment (zani, palbo and/or fulv)-related adverse events (TRAEs) were diarrhea (74%), neutrophil count decreased/neutropenia (62%), stomatitis (41%), asthenia (26%), nausea (24%), and anemia (21%). Grade (Gr) >=3 TRAEs in 2 or more pts included neutrophil count decreased/neutropenia (50%), anemia (6%), diarrhea (6%), and thrombocytopenia (6%). AEs of special interest were all Gr <=2 and included 4 pts with cardiac events (LVEF decrease of >=10% from baseline) and 1 pt with infusion-related reaction. There were no treatment-related serious AEs. Palbo was discontinued for 1 pt due to an AE (AST increase);no pt discontinued zani treatment as a result of AEs. Two deaths occurred: 1 due to disease progression and 1 due to an unrelated AE of pneumonia caused by COVID-19. In 29 pts with measurable disease, the cORR was 34.5% (95% CI: 17.9, 54.3), all responses were cPRs, of which 1 is pending CR confirmation. DOR ranged from 2.3 to 14.9+ mo, with 8 confirmed responses ongoing, and the DCR was 93.1% (95% CI: 77.2, 99.2). Interim median PFS was 11.3 mo (range 0.03-16.7;95% CI: 5.6, not estimable). PFS6 analysis is planned following the completion of enrollment. Conclusion(s): Zani in combination with palbo and fulv shows encouraging antitumor activity with durable responses in heavily pretreated pts and a manageable safety profile. This regimen has the potential to be a chemotherapy-free treatment option in pts with HER2+/HR+ mBC. Enrollment in the study is continuing.
ABSTRACT
Since Coronavirus Disease 2019 (COVID-19) was declared pandemic in March 2020, there have been 545.226.550 cases up to 4 July 2022 (1). Several studies concluded that patients (pts) with cancer are at increased risk of COVID-19 infection, morbidity and mortality. Those undergoing neoadyuvant treatment are at particularly risk of disease progression if chemotherapy or surgery are delayed. Also, is known that a higher NLR (neutrophil to limphocyte ratio) is related to worse outcomes (3). Our hospital is located at the Northwest of Spain and in the last months we noticed a never seen number of infections in cancer population. The aim of this study is to evaluate the severity of COVID19 and its impact on chemotherapy and surgery delay in pts undergoing neoadjuvant chemotherapy breast cancer. METHOD(S): We conducted a ambispective, unicenter, observational study of breast cancer pts, treated with neoadjuvant chemotherapy, between March 2020 and May 2022 at University Hospital A Coruna (Spain). We analyzed type of infection, need of hospitalization, chemotherapy and surgical delay, and its association with tumor type;BRCA germline mutation;clinical stage;treatment;vaccination status;and neutrophils, lymphocytes, and NLR before COVID-19 disease. RESULT(S): During the study period, from 1 March 2020 to 31 May 2022, 183 pts underwent neoadjuvant chemotherapy. A total of 23 (12.5%) pts experienced COVID-19 infection, of which 21 were diagnosed between January and May 2022. The median age was 47,91 years [range 33 - 69 years]. Luminal B HER 2 negative comprised the most common molecular subtype (40.9%), followed by Triple Negative (36.4%), Luminal B HER 2 positive (13.6%), and HER 2 enriched (9.1%). Germline mutations in BRCA account for 13.6% pts. At diagnosis, 4.5%, 72.7%, and 22.7% had stages I, II, and III respectively. Chemotherapy treatments included: paclitaxel followed by AdryamicineCyclophosphamide (AC) (45.4%);carboplatin - paclitaxel - trastuzumab - pertuzumab (18,2%);carboplatin - paclitaxel followed by AC (18,2%);KEYNOTE-756: pembrolizumab/placebo - paclitaxel followed by AC (13.7%);and paclitaxel - trastuzumab - pertuzumab followed by myocet - cyclophosphamide - trastuzumab - pertuzumab (4.5%). The association of G-CSF ocurred in 9 pts (40.9%). 22 pts were fully vaccinated, 8 pts (36.4%) with two doses and 13 pts (59.1%) with three doses. 77.3% pts experienced mild respiratory symptoms with 9.1% hospitalizations. The median duration of delays was 15 days for chemotherapy and 29,58 days for surgery. NLR percentil 25 was associated with COVID-19 type of infection. For those pts with a lower rate, infection was asymptomatic and for those with a higher rate symptoms were moderate (X2= 5,119, p = 0,024). CONCLUSION(S): COVID-19 disease become a high prevalent infection in pts undergoing neoadjuvant breast cancer chemotherapy. Most pts are fully vaccinated and experienced an indolent infection. NLR is an easily measurable and cost-effective parameter that could be useful as a prognostic marker of severity in COVID-19. We will continue to follow-up these pts to see the impact of chemotherapy or surgery delay in pathological complete response and disease-free survival until the congress in December 2022.
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Background: The pattern of new drug approval is changing across the world as shown by the study using Center for Drug Evaluation and Research and European Medicines Agency data in US and UK with more drug approval for anti-cancer and immunomodulator drugs. There is a need to generate similar database for developed South East Asian countries too. Aims and Objectives: This study was conducted for one such country-Singapore for the new drug approval pattern of last 5 years (2017-2021). Material(s) and Method(s): This was a pharmacoepidemiological study, in which government drug regulatory website data available in public domain was searched. The new drug approval data were classified according to active ingredient, drug approval date, new drug application category, indication of drugs, and World Health Organization Anatomic Thoracic Classification. Result(s): In this study, 418 new drug approvals were found in last 5 years in Singapore. From this maximum, drug approvals were given to anti-neoplastic and immunomodulator category drugs. In anti-neoplastic category new drugs approval few examples were Trastuzumab deruxtecan and Tucatinib for breast cancer therapy and Tepotinib and Capmatinib for non-small cell lung cancer therapy. Conclusion(s): This study shows that drug development in anti-cancer drug and immunomodulator is significant in Singapore. This trend is quite matching with other country such as US and UK.Copyright © 2023 Priti Solanky, et al.
ABSTRACT
Background: Patients with HR- advanced/metastatic breast cancer (a/mBC) with a low level of HER2 (immunohistochemistry [IHC] score 1+ or IHC 2+ and negative in situ hybridization [ISH]) have poor prognosis. Combining 1L chemotherapy with immune checkpoint inhibitors can modestly improve outcomes vs chemotherapy alone, but treatment benefit is largely seen in patients with PD-L1+ disease. BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study, evaluating safety and efficacy of D, an anti-PD-L1 antibody, combined with other novel therapies in 1L triple-negative a/mBC, including HR-, HER2-low disease. T-DXd is a trastuzumab-topoisomerase I inhibitor antibody-drug conjugate that improves survival in patients with previously treated HR-, HER2-low mBC (NCT03734029;Modi NEJM 2022). Here, we report updated results of the T-DXd + D combination from BEGONIA. Method(s): Patients with unresectable HR-, HER2-low (per local testing, IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) a/mBC were enrolled in the T-DXd + D arm. Patients eligible for 1L treatment, regardless of PD-L1 status, received intravenous T-DXd 5.4 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. PD-L1, assessed using the VENTANA PD-L1 (SP263) Assay, was defined as high if >= 5% of the tumor area was populated by PDL1-expressing tumor or immune cells. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed objective response rate (ORR;RECIST v1.1);progressionfree survival [PFS];and response duration. Patients included in the efficacy analysis had >= 2 ontreatment disease assessments, progressed, died, or withdrew from the study. Result(s): As of April 8, 2022, 56 patients received T-DXd + D (34 ongoing) and 46 were included in the efficacy analysis. Median (range) follow-up was 10.1 (0-22) months. Median age was 53.5 years, 71% had received prior treatment for early stage BC, and 64% had visceral metastases at baseline. Confirmed ORR was 26/46 (57% 95% CI, 41-71) and unconfirmed ORR was 33/54 (61% 95% CI, 47-74);1/46 patients (2%) had complete and 25/46 (54%) had partial responses. Confirmed response occurred irrespective of PD-L1 expression (PD-L1 high ORR, 5/7 [71%];PD-L1 low, 13/21 [62%];PD-L1 missing, 8/18 [44%]). Median duration of response was not reached;however, 64% of patients remained in response at 12 month follow-up and 73% had an ongoing response at data cutoff. Median PFS was 12.6 months (95% CI, 8-not reached). Adverse events (AEs) were consistent with the agents' known safety, with treatment-related AEs occurring in 49 patients (88%), any Grade 3/4 AEs in 18 patients (32%), and any serious AEs in 10 patients (18%). The most common all-Grade AEs were nausea (41 [73%]), fatigue (26 [46%]), and vomiting (17 [30%]). Adjudicated treatment-related interstitial lung disease/pneumonitis occurred for 5 patients (9%), which were mostly Grade 1 or 2 and 1 case of Grade 5 associated with COVID pneumonia. Seven patients (13%) and 21 patients (38%) had T-DXd dose reduction and dose delay, respectively;22 (39%) had D dose delay. Seven patients (13%) discontinued treatment due to AEs. Conclusion(s): For patients with HR-, HER2-low a/mBC, T-DXd in combination with D in the 1L setting shows manageable safety and promising efficacy including durable responses and an encouraging PFS. Although subgroups were small, responses were observed irrespective of PD-L1 expression. Analysis of additional translational data is ongoing. Funding(s): AstraZeneca/Daiichi Sankyo.
ABSTRACT
Background: The value of increased HER2 gene copy number (GCN) in NSCLC is unclear. In this study we defined its frequency and characterized a cohort of patients harboring it. Methods: Patients with stage IIIB/IV NSCLC enrolled in the Gustave Roussy MSN study (NCT02105168) between Oct. 2009 and Feb. 2016 were screened by FISH (positivity defined as HER2 GCN to centromeres ratio ≥ 2) and tested for other molecular alterations. Descriptive analyses of clinical-pathological data were performed, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: HER2 FISH tested positive in 22 of 250 screened patients (9%). Median age was 60 years (range 47-80), 68% (n=15) were male, 91% (n=20) were current or former tobacco smokers (median exposure 47 pack-year), 64% (n=14) had adenocarcinoma, 18% (n=4) squamous cell and 18% (n=4) large cell carcinoma. 91% (n=20) had an ECOG PS of 0 or 1. Stage IV with extra-thoracic involvement was the most common clinical presentation (64%, n=14). Overall, 95% of patients (n=21) had 1 or 2 metastatic sites at diagnosis (bone 32%, lung 27%, nodes 18%, liver 18%, brain 18%). In 9 patients (41%) 12 concurrent molecular alterations were detected: 5 KRAS mutation (3 G12C, 1 G12D, 1 G61H), 2 HER2 exon 20 insertion, 1 EGFR exon 19 deletion, 1 BRAF V600E mutation, 1 ALK rearrangement, 1 FGFR1 and 1 MET amplification. 18 patients received first-line platinum-based chemotherapy, with 33% (95% CI 16-56) objective response rate and 83% (95% CI 61-94) disease control rate. After a median follow-up of 28 months (95% CI 23-45), median PFS and OS were 5.9 (95% CI 3.4-11.0) and 15.3 (95% CI 10.3-NR) months, respectively. Median PFS was longer in patients with higher GCN. As further line of treatment, 5 patients received trastuzumab: 4 in combination with chemotherapy and 1 as monotherapy, with 1 stabilization of disease as best response. 3 patients received nivolumab (1 partial response and 1 stable disease) and 3 a targeted therapy (anti ALK, EGFR, BRAF). Conclusions: Increased HER2 GCN was found in 9% of patients with unresectable NSCLC, was not correlated to particular clinical characteristics, but frequently occurred with other molecular alterations. Its clinical actionability and the correlation with protein expression deserve further characterization. Clinical trial identification: NCT02105168. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: M. Tagliamento: Other, Personal, Other, Travel grants: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly;Other, Personal, Writing Engagements, Honoraria as medical writer: Novartis, Amgen. E. Auclin: Financial Interests, Personal, Advisory Board: Amgen, Sanofi. E. Rouleau: Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche, Amgen, GSK;Financial Interests, Institutional, Invited Speaker: Clovis, BMS;Financial Interests, Institutional, Funding, Data base: AstraZeneca. A. Bayle: Non-Financial Interests, Institutional, Other, Principal/Sub-Investigator of Clinical Trials: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd, Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi;Financial Interests, Institutional, Other, drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. D. Planchard: Financial I terests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. All other authors have declared no conflicts of interest.
ABSTRACT
Background: The COVID-19 pandemic has led to more than 260 million infections and 55 million deaths as of early December 2021, worldwide. Vaccinating people against COVID-19 is considered as he best approach to overcome the pandemic since COVID 19-vaccines are effective and can reduce the risk of getting and spreading the virus. However, their efficacy and safety in patients with underlying disease such as cancers have not been approved yet. Here we report a cohort study on immunogenicity and safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer, who were vaccinated as a part of a national plan for vaccination of patients with special diseases.
ABSTRACT
Background: Standard of care for HER2+ early/first-line metastatic BC (EBC/MBC) is P + H and concurrent chemotherapy (CT);PH FDC SC offers faster, more convenient admin vs intravenous (IV) P + H. COVID-19 has caused unprecedented strain on healthcare systems and disruption to cancer care;treatment (Tx) at home may: enable pts to continue cancer Tx;reduce exposure to COVID-19;free up hospital resources. This study's main objectives: to enable continuity of care during COVID-19;to assess safety of PH FDC SC given at home. Methods: This is an ongoing single-arm, hybrid, decentralized clinical trial (NCT04395508). Pts with HER2+ EBC/MBC who completed concurrent CT with P + H IV and are receiving/about to receive maintenance P + H IV, PH FDC SC, or H SC are switched to PH FDC SC given at home by a home health nursing provider (HHNP) until disease progression, unacceptable toxicity, pt withdrawal, or physician recommendation (pts with EBC will complete ≤18 cycles). The study endpoint is safety. A subset of pts took part in HARRIET, a substudy of at-home cardiac surveillance with artificial intelligence-guided cardiac ultrasound and optional 6L ECG acquired by an HHNP. Results: Data for 114 pts (1 male) were available at cutoff (Jan 19, 2022): 18 (16%) completed Tx;20 (18%) discontinued;76 (67%) remain on study;79 (69%) had a COVID-19 vaccine while on study. Median age was 49 years;pts were balanced between EBC (n = 55, 48%) and MBC (n = 59, 52%);received a median of 6 (EBC) and 8 (MBC) cycles;and were from metropolitan (n = 109), urban (n = 4), and rural (n = 1) areas. 11 pts tested COVID-19-positive during the Tx phase: 8 continued Tx after appropriate COVID-19 Tx and/or quarantine. Safety is summarized in the table. No new adverse events (AEs) emerged due to home admin. AEs of special interest were grade (gr) 1-2: admin-related reactions (n = 76, 67%), hypersensitivity (n = 5, 4%), cardiac dysfunction (n = 4, 4%), except 1 case of gr ≥3 diarrhea. AEs leading to study Tx discontinuation or interruption/dose reduction occurred in 3 (3%) and 15 (13%) pts. A subset of 7 pts completed at-home cardiac surveillance testing;quantitative assessment of left ventricular ejection fraction was feasible in 3 (43%);5 (71%) preferred at-home surveillance to clinic. Conclusions: In this preliminary analysis, safety of PH FDC SC at home was consistent with the established P + H safety profile, indicating that PH FDC SC at home is a viable option for continuing BC care during and beyond COVID-19.
ABSTRACT
The proceedings contain 5148 papers. The topics discussed include: baseline GP2 immune response as an independent prognostic factor in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) versus. GM-CSF alone after adjuvant trastuzumab in HER2-positive women with breast cancer;fertility preservation decisions and outcomes of young women with breast cancer;adjuvant trastuzumab and vinorelbine (TV) for early-stage HER2+ breast cancer;Outcomes of neoadjuvant (NA) and adjuvant (A) chemotherapy in geriatric patients with stage I-III triple-negative breast cancer (TNBC): a single institution experience;Telehealth delivered Tai Chi intervention for managing aromatase inhibitor-induced arthralgia in breast cancer patients: TaiChi4Joint during the COVID-19 pandemic a pilot study;a prospective real-world study to assess the effectiveness and safety of trastuzumab biosimilar in the adjuvant treatment of HER2-positive breast cancer: preliminary safety results;effectiveness of chemotherapy on prognosis of elderly breast cancer: a retrospective cohort study based on SEER database;and prognostic role of the stromal tumor-infiltrating lymphocytes (TILs) in women with early ER+/HER2+ breast cancer (BC) in whom adjuvant chemotherapy (ChT) was omitted.
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Background: Cardiotoxicity is frequently monitored when anti-HER2 treatment (Tx) is used and is a potential reason for discontinuation. As patients (pts) live longer, improved surveillance via low-interventional management is critical. Advances in digital tools and the impact of COVID-19 are accelerating opportunities for in-home care. We initiated cardiac monitoring at home in a subset of patients from study NCT04395508, which provides continuity of care during the pandemic and home administration of pertuzumab, trastuzumab and hyaluronidase-zzxf (PH FDC SC) for pts with HER2-positive breast cancer. Methods: Pts must be on/will receive maintenance intravenous pertuzumab + trastuzumab/PH FDC SC/subcutaneous trastuzumab post-chemotherapy completion. Up to 36 pts will be enrolled at Memorial Sloan Kettering Cancer Center and selected Mayo Clinic sites. Pts will undergo remote cardiac surveillance by a Home Health Nursing Provider via Caption Artificial Intelligence (AI)-guided ECHO and ECG (KardiaMobile 6L) after a reference in-clinic ECHO and 12-lead ECG. Images and tracing will be assessed centrally. Key objectives are to evaluate feasibility of LVEF assessment at home based on AI-guided cardiac ultrasound images acquired by novice users without prior ECHO experience and to evaluate feasibility, including recording frequency and signal quality, of an AI-guided ECG algorithm at home by the pt with nurse oversight. Results: Enrollment began Aug 2021. Conclusion: For healthcare systems, HARRIET can improve Tx monitoring to avoid premature discontinuation;is a step toward moving away from specialized sites to flexible healthcare delivery and lower cost of care;and can remove logistical, financial and workload barriers of scheduling in-person ECHO readings. For pts, it can optimize care and increase confidence in anti-HER2 Tx and can provide access to specialty care in the comfort of their own home.
ABSTRACT
Introduction: Trastuzumab is a recombinant immunoglobulin G1 monoclonal antibody used to treat HER-2 cancers. Trastuzumabinduced interstitial pneumonitis is a rare adverse effect reported in a few patients. Interstitial pneumonitis presents as symptoms of dyspnea, hypoxia, cough, and fever. If the patient is treated early, corticosteroids can slow or reverse the disease progression. Case: A 41 year old woman presented with dyspnea and a dry cough three weeks after her third cycle of trastuzumab therapy for breast cancer. A diagnosis was made for trastuzumab-induced interstitial pneumonitis after COVID-19, pulmonary embolism, infection, pulmonary edema, and pneumonia were all ruled out. The patient was started on methylprednisolone while inpatient, and transitioned to prednisone for outpatient therapy. Discussion: There are several trials and case reports that report trastuzumab-induced interstitial pneumonitis, but there has been no correlation reported between the patients' history, dosing regimen, or symptom onset. The lack of correlation and limited cases make this adverse effect very difficult to diagnose and monitor. New trials and case reports can bring an insight into contributing factors, symptoms at onset, and treatment for future patients. Conclusion: With the increase in use of trastuzumab therapy, physicians should be aware of how to diagnose and treat the rare adverse reaction of trastuzumab-induced interstitial pneumonitis.
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Fc effector function is one of the main mechanisms of action (MoA) for therapeutic monoclonal antibodies (mAbs). Quantitative measurement of antibody-dependent cellular cytotoxicity (ADCC) is critically required for understanding the Fc function in mAb drug development. Despite the increasing interest and clinical success of the mAb therapeutic, it has been highly challenging to measure their ADCC activity in a reproducible and quantitative manner due to the lack of consistency in current methods that are based on primary PBMCs or NK cells and use tedious assay procedures. To improve ADCC assay precision so they can be validated as potency assay in cGMP laboratories, we developed reporter based ADCC bioassays using engineered effector cell line stably expressing a luciferase reporter and FcγRIIIa (V or F variant) to replace primary PBMC to overcome the assay variation. The ADCC reporter bioassays have been validated according to ICH guidelines by many laboratories and are demonstrated to be suitable for product release and stability studies in a quality-controlled environment. For early research and antibody characterization, we developed an improved PBMC ADCC assay using ADCC-prequalified PBMCs and engineered HiBiT target cells so they can measure the target specific lysis in ADCC. The PBMCs used in the study are isolated from prescreened blood donors and QC tested in ADCC assay. When HiBiT target cells are incubated with an antibody and PBMCs, HiBiT are released to the culture medium where it binds to LgBiT in the detection reagent to form a functional NanoBiT luciferase to generate luminescence signal. This new PBMC ADCC bioassay is simple, homogenous, highly sensitive, and gives a robust assay window. We demonstrate that it can quantitatively measure the potency for mAb drugs in cancer immunotherapy (e.g., rituximab, trastuzumab), and for anti-SARS-CoV-2 spike antibodies in antiviral drug development. Additionally, it shows antibody potency comparable with the ADCC reporter bioassay. In summary, the new PBMC ADCC bioassay using HiBiT target cells can be a valuable tool for early antibody discovery and characterization and also for method bridging study with ADCC reporter bioassay.
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Background: Despite the occurrence of HER2 amplification/overexpression (HER2+) in ~3% to 5% of all patients with metastatic colorectal cancer (mCRC) and up to ~10% of patients with RAS/BRAF wild-type mCRC, there are currently no FDA- or EMA-approved HER2-directed therapies for HER2+ mCRC. Patients with mCRC who progress on early lines of chemotherapy regimens receive limited clinical benefit from current standard-of-care treatments. Tucatinib is a highly selective, HER2-directed, tyrosine kinase inhibitor. The MOUNTAINEER trial (NCT03043313) was initiated to evaluate the efficacy and safety of the investigational combination of tucatinib with trastuzumab in patients with HER2+ mCRC. Here we present results from the primary analysis of MOUNTAINEER. Methods: MOUNTAINEER is a multi-center, open-label, randomised, phase 2 trial conducted in the US and Europe. Eligible patients had HER2+ (one or more local tests: 3+ immunohistochemistry, 2+ immunohistochemistry with amplification by in situ hybridization, or amplification by next‑generation sequencing of tumor tissue) and RAS wild-type mCRC with progression on or intolerance to fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF antibody. Measurable disease and an ECOG performance status of 0–2 were required. Previous HER2-directed therapies were not permitted. The trial initially consisted of a single cohort (Cohort A) to be treated with tucatinib (300 mg PO BID) and trastuzumab (8 mg/kg IV then 6 mg/kg IV every 3 weeks). The trial was expanded to include patients randomised 4:3 to receive tucatinib + trastuzumab (Cohort B) or tucatinib monotherapy (Cohort C). The primary endpoint is confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) in Cohorts A+B. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results: MOUNTAINEER enrolled 117 patients between 08Aug2017 and 22Sept2021. Data cutoff was 28Mar2022. The median age was 56.0 years (range, 24, 77), and baseline characteristics were balanced across cohorts. Eighty-six patients received at least 1 dose of study treatment in Cohorts A+B, and 30 patients received tucatinib monotherapy in Cohort C (total, 116). The overall median duration of follow-up was 16.3 months (IQR, 10.8, 28.2). In Cohorts A+B, the confirmed ORR by BICR was 38.1% (95% CI, 27.7, 49.3). The median DOR was 12.4 months (95% CI, 8.5, 20.5). The median PFS was 8.2 months (95% CI, 4.2, 10.3), and the median OS was 24.1 months (95% CI, 20.3, 36.7). The most common adverse events (AEs) in Cohorts A+B were diarrhoea (64.0%), fatigue (44.2%), nausea (34.9%), and infusion-related reaction (20.9%);the most common AE of grade ≥3 was hypertension (7.0%). Adverse events leading to tucatinib discontinuation in Cohorts A+B occurred in 5.8% of patients and included alanine amino transferase increase (2.3%), COVID-19 pneumonia (1.2%), cholangitis (1.2%), and fatigue (1.2%). No deaths resulted from AEs. Conclusions: In patients with chemotherapy-refractory HER2+ mCRC, tucatinib in combination with trastuzumab was well tolerated with clinically meaningful antitumor activity including durable responses and a median overall survival of 2 years. Tucatinib in combination with trastuzumab has the potential to become a new standard of care for patients with HER2+ mCRC. Clinical trial identification: NCT03043313. Editorial acknowledgement: The authors thank Joseph Giaconia of MMS Holdings, Michigan, USA for providing medical writing support/editorial support, which was funded by Seagen Inc., Bothell, WA, USA in accordance with Good Publication Practice (GPP3) guidelines. Legal entity responsible for the study: Seagen Inc. Funding: Seagen Inc. Disclosures: J. Strickler: Advisory / Consultancy: Seagen, Bayer, Pfizer;Research grant / Funding (institution): Amgen, Roche/Genentech, Seagen. A. Cercek: Advisory / Consultancy: Bayer, Merck, Seagen;Research grant / Funding (institution): Seagen, GSK, Rgenix. T. André: Honoraria (self : Amgen, Astra-Zeneca, Bristol-Myers Squibb, Gritstone Oncology, GlaxoSmithKline, Haliodx, Kaleido Biosciences, Merck & Co., Inc., Pierre Fabre, Sanofi, Servier, Merck & Co., Inc, Servier;Advisory / Consultancy: Astellas Pharma, BMS, Gritstone Oncology, Transgène, Roche/Ventana, Seagen, Merck & Co., Inc, Servier;Research grant / Funding (institution): BMS, Seagen, GSK;Travel / Accommodation / Expenses: BMS, Merck & Co., Inc. K. Ng: Advisory / Consultancy: Seattle Genetics, Bicara Therapeutics, GlaxoSmithKline;Research grant / Funding (institution): Pharmavite, Evergrande Group, Janssen. E. Van Cutsem: Advisory / Consultancy: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks;Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. C. Wu: Research grant / Funding (institution): Seagen. A. Paulson: Research grant / Funding (institution): Seattle Genetics. J. Hubbard: Research grant / Funding (institution): Seattle Genetics. H. Lenz: Honoraria (self): BMS, Bayer, Roche;Advisory / Consultancy: Bayer, Merck, Roche;Travel / Accommodation / Expenses: BMS, Bayer, Merck KG;Shareholder / Stockholder / Stock options: Fulgent. M. Stecher: Full / Part-time employment: SeaGen. W. Feng: Full / Part-time employment: Seagen. T. Bekaii-Saab: Honoraria (self): Royalties: Uptodate;Advisory / Consultancy: Consulting (to institution): Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai and Merck., Consulting (to self): Stemline, AbbVie, Boehringer Ingelheim, Janssen, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, MJH Life Sciences, Aptitude Health, Illumina and Foundation Medicine, IDMC/DSMB: Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe;Research grant / Funding (institution): Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, BMS.;Licensing / Royalties: WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene, WO/2019/055687: METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion. All other authors have declared no conflicts of interest.
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In a phase 3 trial, the antibody–drug conjugate trastuzumab deruxtecan resulted in longer progression-free and overall survival than the physician’s choice of chemotherapy among patients with HER2-low breast cancer. see Original Article, N Engl J Med 2022;387:9-20 Previous Infection and Vaccination in Covid-19 A study in Qatar assessed the effectiveness of previous infection, vaccination, and both against symptomatic SARS-CoV-2 caused by omicron BA.1 and BA.2 and against severe, critical, or fatal Covid-19. see Original Article, N Engl J Med 2022;387:21-34 Brief Report: Porcine-to-Human Cardiac Transplantation In this report, a porcine-to-human heart transplantation is described. Most patients with low-risk pulmonary embolism can be treated with oral anticoagulants. see Clinical Practice Audio, N Engl J Med 2022;387:45-57 The Vaccine-Hesitant Moment The proliferation of vaccine misinformation and its use for political purposes are placing a large number of people at risk in the Covid-19 pandemic and allowing the pandemic to continue. see Review Article, N Engl J Med 2022;387:58-65 Monkeypox Genital Lesions A 31-year-old man presented with a painless genital rash. The midscapular pain was worse at night and lessened with exercise. see Clinical Problem-Solving, N Engl J Med 2022;387:67-73 Genetic Modification in Xenotransplantation In a recent case of xenotransplantation, now described in the Journal, a porcine heart was transplanted into a human patient, an advance made possible through genetic alterations in the animal donor. see Editorial, N Engl J Med 2022;387:79-82 Tympanostomy Tubes for Recurrent Otitis Media This interactive feature about recurrent acute otitis media in a young child offers a case vignette accompanied by two essays, one supporting insertion of tympanostomy tubes and the other supporting conservative medical management. see Clinical Decisions, N Engl J Med 2022;387:83-85 Physicians Spreading Misinformation on Social Media In light of widespread falsehoods about Covid-19 and its treatment and prevention, the American Board of Internal Medicine has informed doctors that disseminating misinformation is grounds for disciplinary sanctions. see Perspective, N Engl J Med 2022;387:1-3 Institutionalizing Misinformation A new bill, the Dietary Supplement Listing Act of 2022, would create the impression of reform in the supplement industry while leaving the current lax regulatory framework largely untouched. see Perspective, N Engl J Med 2022;387:3-5 The Portal What does it mean for a physician who has long maintained her privileged back channels to finally acquiesce to entering her own electronic medical record — and interacting with her doctors — through the patient portal? see Perspective, N Engl J Med 2022;387:5-7 A Call for Antiracist Action The neo-Nazi march on Brigham and Women’s Hospital and attacks on health equity interventions are stark reminders of the obligation of physicians to denounce White supremacism and reaffirm race-conscious antiracism efforts. see Perspective, N Engl J Med 2022;387:e1 Decreased Neutralization of Omicron Subvariants In a small study involving 54 participants, omicron subvariants BA.2.12.1, BA.4, and BA.5 of SARS-CoV-2 were more likely to escape neutralizing antibodies induced by both vaccination and previous infection than were the prior omicron subvariants BA.1 and BA.2. see Correspondence, N Engl J Med 2022;387:86-88 VITT Recurrence after Covid-19 or Vaccine In 69 patients with vaccine-induced immune thrombotic thrombocytopenia caused by anti–PF4 antibodies, subsequent Covid-19 infection or receipt of an mRNA-based vaccine did not induce VITT recurrence. see Correspondence, N Engl J Med 2022;387:88-90
ABSTRACT
Background: In February 2021 Roche announced a new subcutaneous (SC) product to the market;Phesgo. Phesgo was a combination pertuzumab and trastuzumab product which was funded by NHS England for all HER2 positive breast cancer indications. Day case unit capacity is a local and national issue, which has been further highlighted through the COVID19 pandemic with the reduction in treatment chairs due to social distancing and increase in cancer diagnosis and required treatments caused by the backlog from the pandemic. Aim: The aim of this project was to switch all intravenous (IV) pertuzumab and trastuzumab combination patients to SC Phesgo;to alleviate day case unit capacity and to improve the patient experience by June 2021. Methods: A report from CIS Healthcare was run within the electronic prescribing system to highlight all patients and regimes receiving and containing IV pertuzumab;a total of 148 patients network wide. A patient information letter was drafted explaining the change underway which was then emailed or posted out to all patients across the network receiving IV pertuzumab. Alternative regimens containing SC Phesgo were built into the electronic prescribing system;from week commencing 19.04.21 any patient receiving treatment at the tertiary centre (Weston Park Hospital(WPH)) who had received IV pertuzumab and trastuzumab previously would receive SC Phesgo. A patient evaluation questionnaire was distributed to all patients who participated in the switch to SC Phesgo at WPH, to gain qualitative feedback on the switch from the patient perspective. Results: All 148 identified patients receiving IV pertuzumab and trastuzumab were switched to SC Phesgo. Of the 148 patients 81 patients were receiving treatment at WPH, 49 patient evaluation questionnaires were completed;96% of patients were happy with the switch to SC Phesgo. By switching to SC Phesgo there was a weekly average of 48.1 h of chair time saved per week;a 56.9% reduction in chair time for this cohort of treatments and an overall reduction of 5.5% of chair time for the day case unit. In additional to the chair time saved, there was also on average 21.2 nurse hours saved per week;a reduction of 53.5% in nurse time for this cohort and an overall reduction of 4.6% of nurse time for the day case unit. Discussion/Conclusion: By administering SC Phesgo instead of the IV equivalents there have been significant reductions in patient, chair and nurse time. This reduction has help alleviate chair and nurse time capacity issues which were critical prior to the switch in April 2021 due to the COVID19 pandemic. There is an associated cost saving for commissioners despite the number of treatments remaining stable, in March 2021 the cost to the commissioners for all IV pertuzumab and trastuzumab given to breast cancer patients was £320,532.70;in May 2021 this figure (for SC Phesgo) had reduced to £145,956.00. In conclusion the switch the SC Phesgo has improved the patient experience, increased chair and nurse capacity on the day case unit.
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Objective: The systemic anti-cancer therapy (SACT) work stream of the East of England Cancer alliance identified variation in SACT administration times as a potential area to counter the impact of Covid-19 capacity restrictions within chemotherapy day units. The aim is to assess the impact of reducing post infusion observation time of pertuzumab-trastuzumab on efficiency and safety. Methods: The recommendation from East of England Cancer Alliance was to adopt one hour observation post pertuzumab and one hour post trastuzumab for cycle 1, 30 min after each infusion for cycle 2 and 3 and a zero observation time thereafter for patients who have had no reaction. All patients administered IV pertuzumab-trastuzumab between October 2020 and May 2021 were identified. The number of patients experiencing hypersensitivity reactions with the original and reduced observation time was compared. The impact of reduced observation time on chair capacity was also calculated. Results: Of the 26 patients treated with the original observation time between October 2020 to January 2021, two patients reacted and received Hydrocortisone IV 100 mg and Chorphenamine IV 10 mg. Patients continued treatmnet at a slower rate. No patients discontinued treatment due to the reaction. Reactions included flushing, stomach pain, uncontrolled bladder and face swelling. Between February and May 2021,18 patients were treated with reduced observation times and 3 patients reacted. Reactions included hypertension, chills, vomiting and shivering. The total number of patients between the cohorts differs due to the conversion of some patients to Phesgo from April 2021. These patients were managed similarly to the previous cohort with added IV ondansetron and IV metoclopramide. No patient discontinued treatment following the reaction. Chair times savings were 5 h for cycle 1, 2 h for cycle 2 and 3, and 3 h from cycle 4 onwards. In total, 53 chair hours in the chemotherapy day unit were released between February to May 2021. Conclusion: The pressure on chemotherapy units has been exacerbated by staff absence, reduced capacity due to social distancing and use of PPE. Whilst the SPC for trastuzumab states patients should be observed for 6 h post first infusion and for 2 h post subsequent infusions, the implementation of reduced observation times post infusion of pertuzumab-trastuzumab did not impact on patient safety and encouragingly increased the capacity of the day unit by 53 h in four months.
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INTRODUCTION An increasing body of evidence demonstrates that the COVID-19 pandemic of 2020 saw large reductions in the number of US patients being diagnosed with a variety of conditions, including cancer. A previous real world evidence study based upon analysis of CMS claims data showed a large drop in cancer diagnoses across multiple solid tumor diseases and evidence suggesting changes in testing behaviors for these patients over the period of maximal lockdown measures to mitigate spread of infection. Further, the drop in patient numbers had not returned to normal once these measures were relaxed by the end of June. Therefore, we decided to examine CMS data for the entire year of 2020 and focus on a single sub-group in breast cancer, TNBC. These patients have poor prognosis and are relatively intensively managed;it was reasoned that changes in management, especially testing behavior, might be more apparent in this group than in breast cancer patients as a whole. METHODS CMS data for 2019-20 were queried using a proprietary business rule for identifying TNBC cases and then subdivided into 2 groups: those who received a treatment under a "J" HCPCS code and those who had not. Office visits, Level IV surgical pathology (SP) and immunohistochemistry (IHC) were defined by appropriate HCPCS codes. Since all PD-L1 testing is covered by HCPCS code 88360, a claim for 88360 was considered indicative of a PD-L1 test. A decrease in the number of patients during the COVID-19 pandemic Swas defined as a ≥ 10% drop for the value in a given month in 2020 compared to the same month in 2019, as a percentage of the 2019 median value. This is termed the "COVID-Dip". RESULTS Data were gathered from a total of 68, 018 patients, 8, 131 with a J code treatment and 59, 887 without. Results of COVID dip analysis are presented in Table 1. Trastuzumab administration showed an overall decline across the entire study period. While IHC for 88360 showed a COVID dip, administration of atezolizumab and pembrolizumab increased across the study period with administration of nivolumab (collectively immuno-oncology, IO, drugs) remaining relatively constant. 47% of patients receiving IO therapy received a presumed PD-L1 test. There was longitudinal variation in the use of chemotherapy agents but no apparent COVID dip in their use. DISCUSSION There were declines both in patient presentation to doctors' offices, as well as diagnostic testing among TNBC patients during the COVID-19 pandemic of 2020 with differences between those receiving chemotherapy under J codes and those not. There was no evidence of decline in use of chemotherapy under J codes. Increased IO use but declines in IHC testing suggest a greater use of off-label prescribing of these drugs during the pandemic. The decline in presentation to doctors' offices and in testing of patients not receiving J code drugs suggests that these patients may experience significant delays in management of their condition with concomitant increases in morbidity and mortality.
ABSTRACT
Background: SARS-CoV-2 mRNA vaccines have been demonstrated to have robust and durable humoral immune response in healthy individuals. However, their effectiveness in immunocompromised patients, particularly cancer patients, remains less known. Newer data suggests that cancer patients may not mount adequate protective immune response after vaccination. Methods: A retrospective study of patients ≥ 18 years old who had SARS-CoV-2 spike antibody (anti-S Ab) testing after 2 doses of SARS-CoV-2 mRNA vaccines between 12-90 days at Mayo Clinic between January 1, 2021 and May 10, 2021 was performed. The Elecsys Anti-SARS-CoV-2 S electrochemiluminescence immunoassay (Roche Diagnostics, Switzerland) was used to measure the antibody response. Patients with prior COVID-19 infection and patients on immunosuppressive therapy for an indication other than cancer were excluded. Categorical variables were summarized as frequencies (percentages) and continuous variables were reported as median with range. Wilcoxon signed rank test was used to compare continuous variables between groups and Chi-squared or Fisher's exact test was used to compare categorical variables. All tests were two-sided with p value < 0.05 considered statistically significant. The analysis was done using R program version 3.6.2. Results: Among 201 patients, 79 had breast cancer, 91 had a hematologic malignancy, 6 had other solid malignancies, and 25 had no history of cancer. All breast S cancer patients on endocrine therapy or trastuzumab ± pertuzumab without chemotherapy (n=35) had anti-S Ab titer ≥ 500 U/mL. Patients on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) appeared to have low level of anti-S Ab with 28.6% (n=4/14) had anti-S Ab titer ≤ 500 U/mL.Patients on chemotherapy also had low levels of anti-S Ab with 47% (n=14/30) having anti-S Ab titers ≤ 500 U/mL. When combining breast cancer patients on endocrine therapy alone or anti-HER2 therapy with patients without history of cancer as an immunocompetent group, there was significantly greater proportion of immunocompetent patients (97%) who had anti-S Ab titer ≥ 500 U/mL compared with only 8% of patients with hematologic malignancy and 55% of patients with solid malignancy on chemotherapy or CDK4/6i (p < 0.001). Using multivariate logistic regression analysis adjusted for age, gender, and vaccine type, patients with solid malignancies and treatment-related cytopenia, including chemotherapy and CDK4/6i, (OR 35.51 [95%CI 8.38-255.25, p < 0.001]) were more likely than immunocompetent patients to have a suboptimal anti-S Ab results ≤ 500 U/mL. Conclusion: A significant number of breast cancer patients on chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. While CDK4/6i is not commonly considered as immunosuppressive therapy, breast cancer patients on CDK4/6i appeared to have suboptimal response to SARS-CoV-2 mRNA vaccine. Our study also highlights the significance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.