Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

Introduction: The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes. Patients and methods: Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression. Results: At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms. Discussion: Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878

NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines

Carcinosarcomes utérins et ovariens (facteurs pronostiques, survie et traitement)

Contexte : Les carcinosarcomes utérins et ovariens sont des pathologies rares et agressives dont la prise en charge n'est pas standardisée. Matériel et Méthode : Tous les cas de carcinosarcomes de l'ovaire et de l'utérus pris en charge à l'Institut de Cancérologie de l'Ouest René Gauducheau entre 1987 et 2011 ont été rétrospectivement analysés. Résultats : 26 cas de carcinosarcomes utérins et 14 ovariens ont été identifiés. La médiane de survie est de 26 mois pour les localisations ovariennes et de 22 mois pour les primitifs utérins. Au terme de l'étude, 55.5% des patientes ont rechuté. Malgré une intensification thérapeutique depuis les années 2000, les médianes de survie ne sont pas améliorées. Trois facteurs pronostiques de survie indépendants sont retrouvés : le stade FIGO, l'âge brut et la pratique du curage ganglionnaire. Conclusion : Des études multicentriques prospectives randomisées sont nécessaires pour augmenter leur puissance statistique et permettre de définir une stratégie thérapeutique efficace.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy

Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway. The strategy of combined hormone therapy with targeted agents has shown an improvement of progression-free survival (PFS) in several phase II or III trials, including three different classes of drugs: mTOR inhibitors, PI3K and CDK4/6 inhibitors. A recent phase III trial has shown that fulvestrant combined with a CDK 4/6 inhibitor doubles PFS in aromatase inhibitor-pretreated postmenopausal ER+ breast cancer. Other combinations are ongoing to disrupt the interaction between PI3K/AKT/mTOR and cyclin D/CDK4/6/Rb pathways. Despite these successful strategies, reliable and reproducible biomarkers are needed. Tumor genomics are dynamic over time, and blood-based biomarkers such as circulating tumor DNA represent a major hope to elucidate the adaptive mechanisms of endocrine resistance. The optimal combinations and biomarkers to guide this strategy need to be determined

Retifanlimab in patients with recurrent microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) endometrial cancer: Final results from the POD1UM-101 study (Cohort H)

peer reviewe

Clinical and Survival Impact of FDG PET in Patients with Suspicion of Recurrent Ovarian Cancer: A 6-Year Follow-Up

International audienceBACKGROUND: The aim of this retrospective study was to evaluate the contribution of fluorine-18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) to the clinical management and survival outcome of patients (pts) suspected of recurrent ovarian carcinoma, with the hypothesis that early diagnosis of recurrent ovarian cancer may improve overall survival (OS).METHODS: Fifty-three FDG PET/CT scans were retrospectively analyzed for 42 pts. CT and PET/CT findings were confirmed by imaging and clinical follow-up, and/or pathology, which were considered as the gold standard diagnosis. The treatment plan based on CT staging was compared with that based on PET/CT findings. Medical records were reviewed for pts characteristics, progression-free survival (PFS), and OS. PFS and OS were analyzed using the Cox proportional hazards regression model.RESULTS: The final diagnosis of recurrence was established pathologically (n = 16), or by a median clinical follow-up of 6.5 years (range 0.5-7.5) after the PET/CT (n = 37). PET/CT provided a higher detection sensitivity (92.2%, 47/51) than CT (60.8%, 31/51) (p < 0.001). Globally, PET/CT modified the treatment plan in 56.6% (30/53) and in 65.2% (15/23) when the CT was negative prior to PET/CT. In 30 cases, those benefited from a modified treatment plan, these changes led to the intensification of a previous treatment procedure in 83.3% (25/30), and to a reduction in the previous treatment procedure in 16.6% of cases (5/30). The Cox regression multivariate analysis showed that the number of lesions visualized by CT and presence of lung lesions detected by PET/CT were significantly associated with PFS (p = 0.002 and p = 0.035, respectively).CONCLUSION: On account of its impact on treatment planning, and especially in predicting patient outcome, FDG PET is a valuable diagnostic tool for cases of suspected ovarian cancer recurrence

A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy

Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN. Methods. Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m(2) intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups. Results. Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time-to-event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms. Conclusion. Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm