Genomic profiling of primary and recurrent ovarian cancers: A retrospective single-center experience

Background: The oncology landscape is rapidly evolving towards more personalized treatment with the use of molecular-driven therapies. Thus, genomic information has become an integral component of clinical decision-making. This study aims to analyze tumor tissue samples of high-grade serous ovarian cancer (HGSOC) to understand if genomic changes in gene mutation frequencies between primary and relapsing tumors occur and can influence the detection of actionable gene alterations. Method(s): A retrospective study approved by local Ethics Committee was conducted on OC patients treated at Fondazione Policlinico Universitario A. Gemelli, IRCCS. All subjects provided informed written consent for genetic analysis and study participation. FFPE specimens were analyzed by Foundation One CDx, which applies NGS across 324 genes known to be drivers of solid tumors, by sequencing the coding regions of 309 cancer-related genes plus introns from 36 genes. Z-test was used to analyze the mutation frequencies between primary and relapsing tumors. Result(s): 261 patients underwent Foundation Medicine testing. Out of 216 HGSOC, 151 tests were performed on primary lesion, 43 at 1st/2nd recurrence, and 22 at >3 recurrences. Statistically significant changes in BRCA1-2 frequencies were found between primitive lesions and recurrence (p=0.0013). A lower frequency in TP53 (p=0.0013) and a higher frequency of NF1 (p=0.028) and TERC (p=0.027) mutations were shown in tissue collected at recurrence compared to primary lesion. Selective chemotherapy pressure and natural enrichment of better prognosis patients at recurrence may explain the discrepancies between primary and secondary tumors. Conclusion(s): These data suggest the opportunity to re-characterize the molecular profiling of the tumors at the time of recurrence to identify potentially actionable alterations to guide treatment. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Persona , Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, GenMab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Interests, P rsonal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Clinical relevance of NGS analysis in endometrial cancer (EC) management

Background: After the introduction of the molecular classification in EC guidelines, Next Generation Sequencing (NGS) analysis has become an essential tool for EC management. Molecular-driven therapies have also been recently tested, and some have obtained FDA approval. This retrospective cohort study aims to determine the clinical benefit rate (CBR) with the use of targeted therapies based on NGS in ECs patients. Method(s): After approval of the local Ethics Committee, a retrospective study was conducted on EC patients undergoing Foundation Medicine testing at Fondazione Policlinico Universitario Agostino Gemelli IRCCS. All patients provided written informed consent. Formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens were analyzed by Foundation One CDx, which detects 324 genes known to be drivers of solid tumors based on NGS assay. Efficacy outcomes were estimated by the Kaplan-Meier method and expressed as median with its 95% confidence interval. IBM-SPSS v.27.0 software was used for statistical analyses. Result(s): Out of 35 tests performed, 11 patients received a targeted therapy based on actionable mutations detected with the NGS assays. All the 11 patients had been heavily pretreated (>=3 prior lines). One patient died because of COVID-19 and thus was excluded from the analysis. Out of the 10 patients included, targeted therapies showed an overall CBR of 80% in 8 patients (10% CR, 33.3% PR, 40% SD, and 20% PD). 7 patients were treated with a targeted agent belonging to the PI3K pathway, with 3 PR (42.9%), 3 SD (42.9%), and 1 PD (14.2%). 3 patients received PARP inhibitor treatment according to their HRD status, with 1 CR (33.3%), 1 SD (33.3%), and 1 PD (33.3%). Conclusion(s): In our series, an outstanding CBR of 80% was achieved with the use of targeted therapy according to NGS assays in heavily pretreated patients (>=3 prior lines). Our finding underlines the importance of molecular-driven treatments and requires further investigation to confirm these results in terms of clinical benefit in a broader population. Besides, the use of molecular-driven treatments may avoid unnecessary exposure to potentially more toxic therapies and reduce the costs associated with inappropriate treatments. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electr c fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen, Clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Int rests, Personal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

SEROLOGIC RESPONSE TO THE SECOND AND THIRD DOSE OF THE SARS-COV-2 VACCINE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A PROSPECTIVE, CENTRALIZED, MULTICENTER STUDY

Background: Patients with chronic lymphocytic leukemia (CLL) show high infection-related morbidity and mortality due to variable degree of humoral and cellular immune deficiency. High Covid-related mortality and reduced response to the SARS-Cov-2 vaccine have been reported in this patient population. Aims: We carried out a prospective multicenter study to define the rate of CLL patients with an appropriate immune response after the mRNA SARS-CoV2 vaccine (Pfizer-BioNTech;Moderna). Methods: Two-hundred patients with CLL received the first dose of the SARS-CoV-2 vaccine between February and August 2021. Centralized assessment of the anti-SARS-Cov-2 IgG levels (Sero Index, Kantaro Quantitative SARS-CoV-2 IgG Antibody, RUO-R&D System) was performed at the Istituto Superiore di Sanità of Rome, Italy. The median followup of this study is 10.7 months (range 1-12.9). Results: The median age of patients was 70 years, the median IgG level was 635 mg/dl, 61% of patients were IGHV unmutated, and 34% showed TP53 disruption. The majority of patients, 83.5%, were previously treated. Prior treatment included chemoimmunotherapy in 20 (10%) patients, ibrutinib-based therapy in 72 (36%;front-line, 21%;advanced line, 15%), venetoclax-based therapy in 75 (37.5%;front-line, 13.5%;advanced line, 24%). Overall, 135 (77.5%) patients had been previously treated with rituximab, 33 (16.5%) of them within 12 months before vaccination. We assessed the serologic response after the second dose of the SARS-CoV2 vaccine in 195 patients while five were excluded from the analysis (positive test before vaccination, 3 patients;lost to the follow-up, 1;Richter syndrome, 1). Adequate levels of anti-SARS-Cov-2 IgG were detected in 76/195 (39%) patients. Age (<70 vs.≥ 70 years;p <0.0001), CIRS value (<6 vs. ≥6;p=0.005), beta-2 microglobulin (<3.5 vs. ≥ 3.5mg/dl;p=0.04), IgG levels (<550 vs. ≤ 550 mg/dl;p <0.0001), prior treatment (p=0.0001), number of prior treatments (0+1 vs. ≥ 2;p=0.002) and the time between prior rituximab and vaccination (>12 vs. ≤12 month;p=0.001) showed a significant impact on the humoral response. In multivariate analysis only age (OR: 0.92 [95% CI: 0.92-0.97] p=0.0001), IgG levels (OR: 0.28 [95% CI: 0.13-0.58] p<0.001), and the time between prior rituximab and vaccination (OR: 0.10 [95% CI: 0.03-0.37] p=0.001), revealed a significant and independent impact on response. When the analysis was restricted to patients who received targeted therapy, in addition to the younger age (OR: 0.96 [95% CI: 0.92-0.99] p=0.04), higher IgG levels at baseline (OR: 0.31 [95% CI: 0.12-0.79] p=0.014), longer time between the start of ibrutinib or venetoclax-based therapy and vaccination (<18 vs.≥18 months;OR: 0.17 [95% CI: 0.06-0.44], p <0.0001) showed a favorable and independent impact on response. Ninety-three% (182/195) of patients received a third dose of the vaccine. A significant increase in the rate of serologic responses, 51.5% (85/165 evaluated patients, p=0.019), was observed after the booster dose. Moreover, a response was detected in 25% (26/103 evaluated patients) of previously seronegative patients. Summary/Conclusion: In this prospective, multicenter, centralized study, we recorded an effective immune response to the SARS-CoV-2 vaccine in about a third of patients with CLL. Younger age, higher IgG levels, no prior treatment, or stable disease after targeted therapy that suggest preserved immunocompetence were associated with a greater likelihood of achieving an effective immune response. A booster dose of the SARS-CoV-2 vaccine proved beneficial also in previously seronegative patients.

Response of local disease at magnetic resonance after salvage radiotherapy for prostate cancer

Purpose or Objective To assess the pattern of response on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) of presumed local lesions in the setting of salvage radiotherapy (sRT) after radical prostatectomy (RP). Materials and Methods The present prospective study (NCT04703543) was conducted at a single Institution between August 2017 and June 2020. Eligibility criteria were: undetectable prostate specific antigen (PSA) after RP;biochemical recurrence (2 consecutive PSA rises to 0.2 ng/ml or greater);a presumed local failure at DCE-MRI (early/fast enhancing discrete lesion on DCE sequences);no distant metastases at choline-PET/CT;no previous history of androgen deprivation therapy and/or RT. Accrued patients underwent sRT as it follows: 66-69 Gy/30 fractions to the prostatic bed, 73.5 Gy/30 fractions to the local failure at DCE-MRI, 54 Gy/30 fractions to the pelvic nodes (when treated). All patients were offered DCE-MRI 3 months after sRT, and repeated at 3-month intervals until complete disappearance or a maximum of 4 scans. The endpoint of the study, complete response (CR), was defined as the complete disappearance of the target lesion at DCE-MRI. In case of misses before CR, the observation was considered as a persisting partial response (PR). Results 62 patients with 72 nodules at DCE-MRI were accrued. All patients underwent the 1st DCE-MRI at a median of 3.3 months (IQR: 3.1-4.1) after sRT, 33 patients (53.2%) presented a CR, 27 (43,5%) a PR, 2 (3.2%) no response. One patient, implanted with a cardiac device, did not undergo further MRI. Three more patients declined further testing after the 1st (N=2) or the 2nd (N=1) re-evaluation due to the COVID-19 pandemic. Twenty-eight patients underwent a 2nd DCE-MRI after a median of 6.8 months (IQR: 6.5-7.6) from sRT, 20 had a CR, 8 had a PR. After a median time of 10.7 months (IQR: 10.6-12.6), 6 patients were scanned for a 3nd DCE-MRI: 4 CR, 2 PR. The last patient reported a CR after 16.7 months. The majority (94.3%, 95%CI: 88.0-100.0%) of lesions had completely disappeared by the 3rd re-evaluation or a median time of 10.7 months from the end of sRT (Figure).(Figure Presented) Independent predictors of CR at 1st re-evaluation on multivariable analysis were: the volume of the lesion at pre-sRT DCEMRI (OR 0.076, 95%CI 0.009-0.667;p=0.02), the time of re-evaluation from treatment (OR 3.39, 95%CI 1.156-9.993;p=0.026) and the PSA percent decrease at the 5th week of sRT (OR 1.02, 95%CI 0.999-1.050;p= 0.058) (Table). (Table Presented) Receiver-operating characteristic curve (ROC) analysis identified the best cut-off on CR for baseline volume at 0.545 cc, AUC 0.683 (95%CI: 0.548-0.818, p=0.014). The probability of a CR for lesions larger than the cut-off identified at ROC analysis was only around 75% at 10.7 months. Conclusion The vast majority of local lesions disappears at DCE-MRI after sRT, though larger lesions may require more than 10 months from treatment end.

A Clue to Better Select Chronic Lymphocytic Leukemia Patients with Optimal Response to BNT162b2 mRNA COVID-19 Vaccine

Given the immunosuppression of chronic lymphocytic leukemia (CLL), this disease represents a challenging model for assessing the extent of serologic response to mRNA vaccination against severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). In this perspective, we assessed the efficacy of the BNT162b2 mRNA COVID-19 vaccine in 70 CLL pts followed up at single hematological institution. The study was approved by the Institutional Review Board. Serologic testing for SARS Cov2 IgG was performed using the LIAISON® SARS-CoV-2 S1/S2 IgG test (DiaSorin;Saluggia, Italy), a chemiluminescence immunoassay for the quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2. Clinical sensitivity and specificity of assay were 98.7% and 99.5% respectively. Samples were considered negative for antibody titers below 13 AU/ml. Results were compared with those of an age-matched group of subjects with no hematological malignancy (n=57). Patient samples for serology testing were obtained after median time of 14 days (range, 14-28) from the second vaccine dose. Median age of CLL pts was 72 years (range, 63-88) and 71.4% were males. The median time from CLL diagnosis to vaccination was 82.5 mo. (range, 1-280). Twenty-three pts (32.9%) were treatment naïve (TN), 36 (51.4%) on active therapy (i.e., BTKi, 22;anti-BCL2 12;PI3Ki,1;cyclophosphamide,1) and 11 (15.7%) off-therapy (i.e., 8 in complete [CR] or partial remission [PR], and 3 in CLL relapse). Of note, 9 (25.7%) of 35 pts on therapy with a pathway inhibitor (PI) at the time of vaccination had been given an anti-CD20 antibody. The vaccine elicited an antibody-mediated response in 41 (58.5%) of the 70 CLL pts. An inferior response rate [RR] (58.5% vs 100%, OR, 0.012 [0.0007-0.206];P=0.02) and a lower antibody titers (median, 58 AU/ml;range, 1.8-800 vs. 284 AU/ml;range, 14-800;P< 0.0001) were observed in CLL pts in comparison to age-matched subjects with no hematological malignancy. The RR was higher in TN (87%) or off-therapy pts with sustained clinical response (87.5%) in comparison to pts on therapy at the time of vaccination (41.7%)(<0.0001). Similar results were observed when comparison was performed in terms of antibody titers (P=0.02;Kruskall-Wallis test;Fig 1). In comparison to pts treated with a PI as monotherapy, those who received an anti-CD20 antibody in association to PI had a lower antibody response to SARS-CoV-2 vaccine (11.1% vs 53.8%;OR,0.107 [0.011-0.984];P=0.04). In univariate analysis, the following variables were significantly associated with serological response to SARS-CoV-2 vaccination: early Rai stage (i.e.,0-I) (OR, 0.36 [0.13-0.97];P=0.04), mutated IGHV status (OR,0.30 [0.10-0.88];P=0.02), lack of active therapy - which comprised TN and off-therapy pts with sustained response - (OR,0.09 [0.03-0.32];P<0.0001), and no anti-CD20 antibody exposure preceding vaccination (OR, 013 [0.01-1.23];P=0.04). Levels of immunoglobulins or absolute values of CD3,CD4,CD8, and CD16/CD56 cells measured before the first COVID-19 vaccination were not associated to vaccine response. Of note, in pts who experienced a serological response a concomitant increase of the absolute of CD16/CD56 positive cells was observed (P=0.02). Finally, Rai stage (OR, 0.19 [0.05-0.79];P=0.02) and treatment status (OR, 0.06 [0.02-0.27];P<0.0001) were independent predictors of response in multivariate analysis. We used these factors to build a score that identified pts with different pattern of response to vaccine. Serologic response to SARS-CoV-2 vaccination was 100% in pts with no factor (n=21), 45% in pts. with one factor (n=38) and 36% in pts with two factors (n=11) (P<0.0001). In agreement with results of recent studies (Herishanu et al, Blood 2021;Roeker et al, Leukemia 2021;Perry et al, Blood Cancer J. 2021;Benjamini O et al, Haematologica 2021 ) our findings suggest that antibody-mediated response to COVID-19 vaccination is significantly reduced in CLL and influenced by disease activity and treatment status. The serological response to SARS-CoV-2 v ccination observed in pts. with early disease with no need of therapy may help to identify CLL pts who are expected to achieve an optimal response to COVID-19 vaccine similarly to age- and sex-matched controls. [Formula presented] Disclosures: Molica: Astrazeneca: Honoraria;Abbvie: Consultancy, Honoraria;Janssen: Consultancy, Honoraria.

Antineoplastic treatment class modulates COVID-19 mRNA-BNT162b2 vaccine immunogenicity in cancer patients: a secondary analysis of the prospective Vax-On study.

BACKGROUND: Preliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity. METHODS: The Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties. RESULTS: Three hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine. CONCLUSIONS: Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.

Covid-19 analysis from the multicenter, prospective, observational invidia-2 study (Influenza Vaccine Indication During Therapy With Immune Checkpoint Inhibitors: A Transversal Challenge)-a ficog study

Background: The prospective, multicenter, observational INVIDIa-2 study was designed to investigate the clinical efficacy of influenza vaccination in advanced cancer patients receiving immune checkpoint inhibitors (ICIs) from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until April 30, 2020. All ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the INVIDIa-2 study prospectively recorded all the COVID-19 ILI events. Methods: Patients were included in this non-prespecified COVID-19 preliminary analysis if potentially exposed to Sars-Cov-2 infection, namely alive on January 31, 2020, when the Italian government declared the National emergency. The incidence of confirmed COVID-19 was assessed among patients with ILI symptoms, describing the hospitalization rate and mortality. Cases with clinicalradiological diagnosis of COVID-19 without laboratory confirmation (COVID-like ILIs), were also reported. The COVID-incidence was exploratively compared basing on influenza vaccination. Results: 1260 patients receiving ICI were enrolled between October 2019 and January 2020;955 patients were analyzed according to the inclusion criterion. Of them, 66 patients had ILI from January 31, to April 30, 2020. 9 were COVID-19 ILIs with laboratory test confirmation. The COVID-19 ILI incidence was 0.9% (9/955 cases), with hospitalization rate of 100% and mortality rate of 67%. Including 5 COVID-like ILIs, the overall COVID-19 incidence was 1.5% (14/955), with hospitalization in 100% of cases and mortality rate of 64%. COVID-19 incidence was 1.2% for patients vaccinated against influenza (6/482 cases) and 1.7%, among unvaccinated patients (8/473 including 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference was not statistically significant, and the clinical trend in favor of vaccinated patients was lost when considering only confirmed COVID-19 (1.2% in vaccinated vs 0.6% in unvaccinated patients, p = 0.33), probably due to the greater presence of male and elderly patients in the vaccinated group (p = 0.009). Conclusions: We obtained the first prospective epidemiological data about symptomatic COVID-19 in advanced cancer patients receiving ICIs. The overall symptomatic COVID-incidence is meaningful, requiring hospitalization in all cases and leading to a high mortality rate, likely due advanced cancer more than to ICI therapy [Mengyuan Dai, Cancer Discov 2020].

Social distress among medical oncologists and other healthcare professionals during the first wave of COVID-19 pandemic in Italy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread to every country around the world taking on pandemic proportions. Since 8 March 2020, the Italian government ordered a nationwide lockdown with unavoidable social isolation. Healthcare professionals (HCPs) represent the most physically and emotionally involved category. The aim of this study is to assess the social distress among HCPs in Italy. PATIENTS AND METHODS: In this online, totally anonymous survey, 24 multiple choice questions were posed to medical staff employed in the Italian Healthcare System during the COVID-19 pandemic. Data collection was performed from 30 March to 24 April 2020. RESULTS: A total of 600 HCPs completed the questionnaire. The majority of respondents expressed the fear of being at higher risk of contagion than the general population (83.3%) and the weighty concern of infecting their families (72.5%). An insufficient supply of personal protective equipment (PPE; P = 0.0003) and inadequate training about procedures to follow (P = 0.0092) were seen to significantly coincide with these worries. More than two-thirds declared a change in family organisation, which showed a significant correlation with the concern of infecting their relatives (P < 0.0001). CONCLUSIONS: This is the first Italian survey on social distress among HCPs during the COVID-19 pandemic. The unavailability of PPE, screening procedures and adequate training strongly affected HCPs' emotional status. Although there was a predominance of oncologists (especially from the North of Italy), which impairs the generalisation of our findings, this survey underlined the social impact that this health emergency has had on HCPs.

Influenza-like illness and SARS-Cov-2 in the multicenter, prospective, observational INVIDIa-2 study (INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: A transversal challenge): A FICOG study

Background: The susceptibility of advanced cancer patients treated with immune checkpoint inhibitors (ICI) for viral infections has not been investigated. Currently, there are no robust data supporting the efficacy, safety and recommendation for influenza vaccination in cancer patients receiving ICI. Methods: The prospective, multicenter, observational INVIDIa-2 study investigated the clinical efficacy of influenza vaccination in advanced cancer patients with solid tumors receiving ICI between October 2019 and January 2020. The incidence of influenza-like illness (ILI, primary endpoint) was observed until April 30, 2020. Secondary endpoints included a non-prespecified analysis for COVID-19. Results: The study enrolled 1279 patients;1188 were evaluable. Of them, 11 patients developed ILI symptoms with confirmed diagnosis of COVID-19 (incidence of 0.9% and lethality of 72%, irrespective of the flu vaccination). Of the remaining 1177 patients, 574 received flu vaccination (48.8%). The ILI incidence was 7.7% (91 patients of 1177). Patients receiving the flu vaccine were significantly more frequently elderly (p<0.0001), former or active smokers (p<0.0001), affected by lung cancer (p=0.017) and by non-cancer comorbidities (p<0.0001) when compared to unvaccinated patients. The flu vaccine did not prevent ILI in the study population, irrespective of the vaccine type (quadrivalent vs trivalent, adjuvated vs non): the incidence of ILI was 8.2% in vaccinated vs 7.3% in unvaccinated patients (p=0.57). ILI complications were significantly less frequent for patients receiving flu vaccine (12.8% vs 40.9%, p=0.002). Hospital admission due to ILI occurred for 10 patients (11% of ILI cases;7 were unvaccinated). The ILI lethality was 2.2% (2 of 91 patients, both unvaccinated). Among vaccinated patients, those receiving adjuvated vaccines had lower incidence of ILI (4.8% vs 9.9%, p=0.046). Conclusions: Flu vaccination was not effective for ILI prevention, nor for COVID-19. Nevertheless, it reduced ILI complications, with no ILI-related deaths in vaccinated patients. We recommend the vaccine in ICI-treated cancer patients. Clinical trial identification: Eudract number of the trial: 2020-002603-18. Legal entity responsible for the study: FICOG Federation of Italian Cooperative Oncology Groups. Funding: FICOG (Federation of Italian Cooperative Oncology Groups, promoter and main sponsor), in turn funded by Seqirus UK and Roche S.p.A. for the present study. Disclosure: M. Bersanelli: Research grant/Funding (self), Research grant/Funding (institution), for the present study: Seqirus and Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, for other activities outside the present study: Pfizer, BMS, Novartis. S. Buti: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb (BMS), Pfizer;MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. U. De Giorgi: Research grant/Funding (institution): AstraZeneca, Roche, Sanofi;Honoraria (self): Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi. P. Bonomo: Honoraria (self): Merck Serono, Angelini Pharma,. All other authors have declared no conflicts of interest.