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Simple Summary: Elderly cancer patients over the age of 80 years represent a growing population; these are notably melanoma patients since 25% of cases are diagnosed after 75 years of age. Establishing the best therapeutic strategies for older patients with melanoma is a challenge since this subpopulation has poor disease-specific outcomes, partly due to age-related variations in therapeutic management. Regarding mono-immunotherapy, either with anti-CTLA-4 or anti-PD-1, several studies have shown similar tolerability outcomes in older and younger patients. However, there are limited data in very elderly patients, especially those treated with immunotherapy combinations. The aim of this multicenter retrospective study is to analyze the prescribing patterns and the safety profile of nivolumab combined with ipilimumab in a cohort of octogenarian and nonagenarian melanoma patients in a real-life setting. The results indicate that the prescribing patterns are very heterogeneous in patients aged over 80 years old, highlighting the lack of clear therapeutic guidelines in the elderly population. In this cohort, the toxicity data did not show a high frequency of severe immune-related adverse events. Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3–93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question. [ABSTRACT FROM AUTHOR]

Simple Summary: Many patients with chronic-phase chronic myeloid leukemia (CP-CML) treated with a tyrosine kinase inhibitor (TKI) experience disease progression and switch to another TKI, but each switch yields diminishing returns. To gain insight into the burden of repeated TKI treatment failures, this study analyzed the characteristics, treatment and disease patterns, and outcomes of adult patients with CP-CML in France whose disease progressed after treatment with two or more TKIs between 2006 and 2021. Patients switched TKIs up to six times; in many cases, treatment with the first and second TKIs lasted <2 years. On the other hand, patients who showed a good response to their third TKI had a lower risk of death. These findings provide a broad view of CP-CML treatment in France over the last 15 years and highlight the need for more effective therapies early in the treatment course that can improve outcomes for patients with CP-CML. This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3–10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study investigated newly diagnosed coronary artery disease (CAD) in prostate cancer patients treated with Androgen Deprivation Therapy and who underwent cardio-onco evaluation at a Cancer Institute. The cardio-onco evaluation included a systematic evaluation of coronary status. Among the 34 patients evaluated, 20.6% were diagnosed with CAD, often asymptomatic with a median diagnosis time of 5 months. Of the 27 patients without CAD, 44.4% underwent a therapeutic intervention by the cardiologist. Our results underscore of CAD screening in this population; however, further research is needed to determine whether routine CAD screening for these patients would result in significant clinical benefits. Background: Given the potential cardiovascular risks of androgen deprivation therapy (ADT), it is essential to identify patients who may be at an increased risk for coronary artery disease (CAD). Despite the recent ESC recommendations, there is no consensus on when to refer a patient to a cardiologist for further evaluation. Objective: To report on new diagnoses of CAD in patients with prostate cancer (PCa) requiring ADT who underwent a systematic cardio-onco evaluation with an assessment of their coronary status. Design, Setting, and Participants: This is a retrospective, monocentric study that included patients with PCa who had completed a cardio-onco evaluation with an assessment of their coronary status in the cardio-oncology department at the Western Cancer Institute, Nantes, between January 2019 and August 2022. Intervention: The baseline cardio-onco evaluation included a physical exam, transthoracic echography, and electrocardiogram, followed with a systematic evaluation of their coronary status. Outcome Measurements and Statistical Analysis: The primary objective was to determine the incidence of newly diagnosed CAD. The secondary objective was to evaluate the number of changes in cardiovascular treatment. Results and Limitations: Among the 34 patients who underwent cardio-onco evaluation, 7 (20.6%) were diagnosed with CAD, with a median time to diagnosis of 5 months. Most patients were asymptomatic, with one who experienced a myocardial infarction. Of the 27 patients without CAD, 44.4% underwent a therapeutic intervention by the cardiologist, with no cardiac deaths during follow-up. Overall, 55.9% of patients had a therapeutic intervention after the cardio-onco evaluation. Conclusions: The high incidence of newly diagnosed CAD in asymptomatic patients supports the need for screening for CAD in this population. Further research is needed to determine whether routine screening for CAD in patients receiving ADT would result in significant clinical benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with venous thromboembolism events in the context of cancer should receive anticoagulants for at least 6 months. Both low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are considered in international guidelines, with a different approach. To investigate the determinants of decision, at thrombosis diagnosis and after 6 months, and the practices when facing special situations, such as venous thromboembolic recurrence or thrombocytopenia, we designed a survey among specialists of cancer-associated thromboembolism, including vignettes about patients with different cancer sites and questions. We considered points related to cancer disease, anticancer treatments and characteristics of patients. Low molecular weight heparins (LMWHs) are recommended by international guidelines for at least 6 months in patients with cancer-associated thromboembolism (CAT). Direct oral anticoagulants (DOACs) have been proposed as an alternative to LMWH. In clinical practice, the specialists in charge of CAT have to decide which anticoagulant to prescribe. An electronic survey tool, including vignettes and questions, was sent to members of the French Society of Vascular Medicine, the French-speaking association for supportive care in oncology and the Investigation Network On Venous Thrombo-Embolism. Among the 376 respondents, LMWHs were reported as the first choice by most specialists. The prescription of DOACs within the first 3 weeks of CAT diagnosis was highly dependent on the cancer site: 5.9%, 18.6% and 24.5% in patients with locally advanced colorectal, lung and breast cancer, respectively. The determinants were mostly related to cancer (site and stage or evolution) and to anticancer treatments. For 61% of physicians, some anticancer treatments were contraindications to DOACs. However, almost 90% of physicians considered switching to DOAC after a median 3-month period of LMWHs. In daily practice, LMWHs and DOACs are now considered by specialists of CAT; the decision is mostly driven by the site of cancer. The role of anticancer treatments in the decision remains to be investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral etoposide (VP16), an inhibitor of topoisomerase-II, has demonstrated clinical activity in metastatic breast cancer (MBC). To our knowledge, oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not been evaluated before. This combination is biologically relevant, as TOP2A, the gene encoding topoisomerase II, is often co-amplified with ERBB2. We report a retrospective analysis of the impact of oral VP16-trastuzumab on HER2+ MBC patients, together with TOP2A/ERBB2 co-amplification status, assessed through shallow whole genome sequencing. In addition to its low cost and convenience, the oral VP16-trastuzumab regimen has shown a satisfactory activity and excellent tolerability. Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated. Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available. Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4–4.7]) and 11.3 months (95% CI [8.3–25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification. Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC. [ABSTRACT FROM AUTHOR]