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Background: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. Patients and methods: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. Results: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. Conclusion: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this protocol in ongoing trials and the association of cisplatin, docetaxel, and cetuximab appears to be the most efficient. The human papilloma virus is very likely a favorable prognostic factor. Immunotherapy with nivolumab or pembrolizumab is now a new standard of treatment in second line after yielding an improvement in overall survival, but predictive markers of efficacy are needed to refine the selection of patients. The combination of paclitaxel and buparlisib appears to be promising.

Introduction: Bevacizumab-containing therapy is considered a standard-of-care front-line option for stage IIIB–IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non-interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real-world setting.Patients and Methods: Eligible patients were aged ≥ 18 years with planned bevacizumab-containing therapy for newly diagnosed ovarian cancer. The primary objective was to assess the safety profile of front-line bevacizumab in routine clinical practice; secondary objectives were to describe patient characteristics, indications/contraindications for bevacizumab, treatment regimens and co-medications, follow-up and monitoring, progression-free survival, and treatment at recurrence. In this non-interventional study, treatment was administered as chosen by the investigator and participation in the trial had no influence on the management of the disease.Results: Of 1,290 patients screened between April 2013 and February 2015, 468 were eligible. Most patients (86%) received bevacizumab 15 mg/kg every 3 weeks or equivalent, typically with carboplatin (99%) and paclitaxel (98%). The median duration of bevacizumab was 12.2 (range 0–28, interquartile range 6.9–14.9) months; 8% of patients discontinued bevacizumab because of toxicity. The most common adverse events were hypertension (38% of patients), fatigue (35%), and bleeding (32%). There were no treatment-related deaths. Most physicians (90%) reported blood pressure measurement immediately before each bevacizumab infusion and almost all (97%) reported monitoring for proteinuria before each bevacizumab infusion. Median progression-free survival was 17.4 (95% CI, 16.4–19.1) months. The 3-year overall survival rate was 62% (95% CI, 58–67%). The most commonly administered chemotherapies at recurrence were carboplatin and pegylated liposomal doxorubicin.Discussion: Clinical outcomes and tolerability with bevacizumab in this real-life setting are consistent with randomized trial results, notwithstanding differences in the treated patient population and treatment schedule.Clinical Trial Registration:ClinicalTrials.gov, Identifier NCT01832415.

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Background: a specific subset of metastatic triple-negative breast cancers (mTNBC) is characterized by homologous recombination deficiency (HRD), leading to enhanced sensitivity to platinum-based chemotherapy. Apart from mutations in BRCA1/2 genes, the evaluation of other HRD-related alterations has been limited to date. As such, we analyzed data from mTNBC patients enrolled in the ProfiLER-01 study to determine the prevalence of alterations in homologous recombination-related (HRR) genes and their association with platinum sensitivity. Methods: next-generation sequencing and promoter methylation of BRCA1 and RAD51C were performed on tumors from patients with mTNBC, using a panel of 19 HRR genes. Tumors were separated into three groups based on their molecular status: mutations in BRCA1/2, mutations in other HRR genes (BRCA1/2 excluded) or BRCA1/RAD51C promoter methylation and the absence of molecular alterations in HRR genes (groups A, B and C, respectively). Sensitivity to platinum-based chemotherapy was evaluated through the radiological response. Results: mutations in BRCA1/2 were detected in seven (13.5%) patients, while alterations in other HRR genes or hypermethylation in BRCA1 or RAD51C were reported in 16 (30.7%) patients; furthermore, no alteration was found in the majority of patients (n = 29; 55.8%). Among 27 patients who received platinum-based chemotherapy, the disease control rate was 80%, 55% and 18% (groups A, B and C, respectively; p = 0.049). Regarding group B, patients with disease control exhibited mutations in FANCL, FANCA and the RAD51D genes or RAD51C methylation; Conclusion: mutations in HRR genes and epimutations in RAD51C were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in BRCA1/2, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.

Concomitant chemotherapy with cisplatin (100 mg/m every 3 weeks) improves outcome for high-risk patients in the postoperative setting and for inoperable disease. Toxicity is increased. Other schemes of potentiation are sometimes used to reduce toxicity, but efficiency is diminished. Cetuximab also improves outcome, but there has been no direct comparison with cisplatin. Immunotherapy is currently being evaluated in association with radiation therapy. Trials are ongoing to evaluate the impact of de-escalation for human papillomavirus-positive patients. The association of docetaxel, cisplatin, and 5-fluorouracil is the standard of induction; it is also the standard treatment for laryngeal preservation. Many trials have attempted to compare the concomitant approach with the sequential treatment; none have managed to show a difference between the two. After induction chemotherapy, there is still no standard of potentiation of radiotherapy.