A real-life study of daratumumab combinations in newly diagnosed patients with light chain (AL) amyloidosis.

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.

PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.

Objective: This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Methods: Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. Conclusion: In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

Trifluridine-tipiracil plus bevacizumab versus trifluridine-tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study.

BACKGROUND: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL. METHODS: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375). FINDINGS: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown). INTERPRETATION: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial. FUNDING: Bristol-Myers Squibb. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab - study protocol.

BACKGROUND: Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy. METHODS: The Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life. DISCUSSION: From a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05652673, registration date: 08-12-2022.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Efficacy and safety of eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with anthracycline/taxanes.

BACKGROUND: This prospective real-world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China. PATIENTS AND METHODS: In this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo-/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed. RESULTS: One hundred and thirty-four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3-15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first- or second-line treatment was significantly better than those who received eribulin as ≥3-line treatment (6.9 months [95% CI: 3.2-8.8] vs. 4.0 months [95% CI: 3.4-4.6], p = 0.006). The mPFS of patients with triple-negative, HER2-positive, and HER2(-)/HR(+) was 3.4 (95% CI: 2.7-4.1), 6.2 (95% CI: 2.3-10.1) and 5.0 months (95% CI: 4.1-5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6-6.3] vs. 4.0 months [95% CI: 3.3-4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non-TNBC receiving eribulin as ≤2-line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment-related adverse events. CONCLUSION: Eribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real-world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

The efficacy and safety of apatinib combined with S-1 for advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Advanced gastric cancer (AGC) that does not respond to first-line therapy poses a challenge to clinical management. The objective of this study was to compare the efficacy and safety of apatinib combined with S-1 in second-line and above treatment of AGC. METHODS: Cochrane Library, Science Direct, EMBASE, PubMed, and CNKI were searched for randomized controlled trial until August 2023. Only patients who met "Standardized Diagnosis and Treatment Guide for Gastric Cancer" were included in the study. The accurate data and distinguishing between follow-up time and drug dose were extracted to reduce heterogeneity and the risk of bias of the included trials was evaluated according to the Cochrane Handbook. Finally, the survival benefit of the treatment was evaluated based on clinical response rate, survival period, biochemical index, and adverse event occurrence in the trial. RESULTS: The meta-analysis included 29 randomized controlled trials involving 2149 participants. Statistically significant increases in clinical effective rate (odds ratios = 2.61, 95% confidence interval [2.13-3.20], P < .00001) and disease control rate (odds ratios = 3.16, 95% confidence interval [2.54-3.94], P < .00001) were found when apatinib combined with S-1, and also had obvious advantages in reducing tumor markers and regulating immune factors. In addition, apatinib combined with S-1 significantly increased the risk of hypertension but reduced damage to liver function, while the improvement of other adverse events was not pronounced. DISCUSSION: Apatinib combined with S-1 is more effective and safe for second-line and above treatment of AGC. This study minimized the conclusion bias caused by the basic data sources, but more high-quality studies are still needed to validate these conclusions.

heredERA Breast Cancer: a phase III, randomized, open-label study evaluating the efficacy and safety of giredestrant plus the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with previously untreated HER2-positive, estrogen receptor-positive locally advanced or metastatic breast cancer.

BACKGROUND: HER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC. First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I-II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression. METHODS: This phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+ locally advanced (LA)/mBC into the induction phase (fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes. DISCUSSION: heredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022). SPONSOR: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland.

Treatment outcomes of pediatrics acute myeloid leukemia (AML) and associated factors in the country's tertiary referral hospital, Ethiopia.

BACKGROUND: Pediatric Acute Myeloid Leukemia (AML) is a major cause of morbidity and mortality in children with cancer in Africa and other developing continents. Systemic chemotherapy and effective supportive care have significantly contributed to increased survival rates of pediatric AML in developed countries reaching approximately 70%. There is a paucity of contextual data regarding overall and event-free survival outcomes in children with acute myeloid leukemia in developing countries and most centers in Africa provide palliative care. The objective of this study was to assess the overall survival, event-free survival, and associated factors in pediatric AML patients treated in Ethiopia. METHODS: This retrospective study was conducted on Pediatric AML patients treated at Tikur Anbessa Hospital between January 1, 2015, and May 30, 2022. The socio-demographic profile of patients, the clinical characteristics, the biochemical and morphological subtypes of AML were analyzed using SPSS version 25. The Kaplan-Meier survival curve was used to estimate the probabilities of overall and event-free survival. Statistical significance was set at p < 0.05. RESULTS: A total of 92 children with AML were included in this study. The median age at diagnosis was 7 years (interquartile range: 5-10 years) with a slight male predominance. The median duration of symptoms was one month. Neutropenic fever (56, 86.2%) was the most common complication during treatment. About 29.3% of the patients succumbed to early death. The corresponding 1-year and 3-year OS probabilities were 28.2% and 23% respectively. The median event-free survival time for all pediatric AML patients was one-month (95% CI: 0.77-1.23). The determinants of poorer survival outcomes were FAB subtype, type of protocol used, and signs of CNS involvement (p < 0.05). CONCLUSION: The survival rates of children from AML were low in the study setting. More than 25% of AML patients succumbed to early death, and febrile neutropenia was the most common complication. Effective supportive and therapeutic measures should be taken to manage febrile neutropenia and to prevent early death in AML patients.

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies.

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis.

BACKGROUND: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. PATIENTS AND METHODS: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. RESULTS: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). CONCLUSIONS: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Background and aim: Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Methods: Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Results: Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. Conclusion: The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

Prevalence of anticipatory nausea and vomiting in breast cancer patients undergoing highly emetogenic chemotherapy.

OBJECTIVE: Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist. METHODS: This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2. RESULTS: From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003). CONCLUSION: The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.

Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. METHODS: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. RESULTS: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. CLINICALTRIALS: gov NCT04169672.

Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

Regorafenib with immunotherapy versus regorafenib alone as second-line treatment for hepatocellular carcinoma: A multicenter real-world study.

INTRODUCTION: Regorafenib remains the standard and widely used second-line strategy for advanced hepatocellular carcinoma (HCC). There is still a lack of large-scale multicenter real-world evidence concerning the concurrent use of regorafenib with immune checkpoint inhibitors (ICI). This study aims to evaluate whether combining regorafenib with ICI provides greater clinical benefit than regorafenib monotherapy as second-line therapy for advanced HCC under real-world circumstances. PATIENTS AND METHODS: The study included 208 patients from five medical facilities. One hundred forty-three patients received regorafenib plus ICI combination therapy, while 65 patients received regorafenib monotherapy. Propensity score matching (PSM) analysis was employed. RESULTS: The regorafenib plus ICI group demonstrated significantly higher objective response rate (24.3% vs. 10.3%, after PSM, p = 0.030) and disease control rate (79.4% vs. 50.0%, after PSM, p < 0.001) compared to the regorafenib monotherapy group based on mRECIST criteria. Median progression-free survival (7.9 vs. 3.2 months, after PSM, p < 0.001) and overall survival (25.6 vs. 16.4 months, p = 0.010, after PSM) were also considerably longer in the regorafenib plus ICI group. The incidence of Grades 3-4 treatment-related adverse events (TRAEs) was marginally greater in the regorafenib plus ICI group than in the regorafenib group (23.8% vs. 20.0%, p = 0.546). Notably, there were no instances of treatment-related mortality or emergence of new TRAEs in any treatment group. CONCLUSION: The combination of regorafenib and ICI shows potential as a viable second-line treatment for advanced HCC, exhibiting favorable efficacy while maintaining a tolerable safety profile in contrast to regorafenib monotherapy.

Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial.

BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.

Treatment of patients with carcinomas in advanced stages with 5-fluorouracil, folinic acid and pyridoxine in tandem.

The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.

Influence of (C1236T and C3435T) Polymorphisms of ABCB1 Gene on Chemotherapy Treatment Outcome and Toxicity in Breast Cancer Patients.

BACKGROUND: ATP Binding Cassette Transporters (ABCB1) gene plays an important role in transport of different metabolites and anticancer drugs across the cell membrane. There is lack of knowledge on ABCB1 gene polymorphism and its correlation with Adriamycin or paclitaxel based chemotherapy induced toxicity in breast cancer patients. Therefore in this study, we explored the correlation of ABCB1 polymorphisms gene on response and toxicity in adriamycin and paclitaxel based chemotherapy in breast cancer patients from Indian population. METHODS: Two hundred BC patients receiving Adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in ABCB1 gene (C1236T, C3435T) were studied by PCR and RFLP analysis. RESULTS: The univariate logistic regression analysis showed statistically significant negative association with protective effects of ABCB1 (C3435T) polymorphism with heterozygous genotype (OR=0.34, 95% CI: 0.13-0.89; p=0.027), homozygous variant genotype (OR=0.31, 95% CI: 0.10-0.99; p=0.049) and combined C/T+T/T genotypes (OR=0.33, 95% CI: 0.13-0.79; p=0.013) in relation with severe toxicity of chemotherapy induced nausea and vomiting in breast cancer patients treated with Adriamycin chemotherapy. The 3435 C>T polymorphism of ABCB1 gene with heterozygous C/T genotype showed significantly negative association (OR=0.37, 95% CI: 0.14-0.96; p=0.042) with peripheral neuropathy in patients treated primarily with paclitaxel thereafter Adriamycin. CONCLUSION: The findings obtained from this study revealed significant association of ABCB1 3435 C>T polymorphisms with non-hematological toxicity in response to adriamycin and paclitaxel based chemotherapy.