Durvalumab and tremelimumab in combination with metronomic oral vinorelbine for recurrent advanced cervical cancer: an open-label phase I/II study.

Background: The MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced cervical cancer cohort.

Methods: Patients received tremelimumab (intravenously, 75 mg, every four weeks (Q4W); four cycles max) plus durvalumab (intravenously, 1,500 mg, Q4W; 26 cycles max) and metronomic oral vinorelbine (40 mg, every three weeks (3QW)) until disease progression.

The impact of introducing deep learning based [F]FDG PET denoising on EORTC and PERCIST therapeutic response assessments in digital PET/CT.

Background: [F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up.

Results: 110 patients referred for baseline and follow-up standard digital [F]FDG PET/CT were prospectively included.

Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma.

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8PD-1 T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.

Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial.

This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional.

Carboplatin in metastatic castration-resistant prostate cancer patients with molecular alterations of the DNA damage repair pathway: the PRO-CARBO phase II trial.

Introduction: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity.

Inequality factors in access to early-phase clinical trials in oncology in France: results of the EGALICAN-2 study.

Background: Investigation of the disparities in the access to experimental treatment in early-phase clinical trials is lacking. The objective of the EGALICAN-2 study was to identify the factors underpinning such inequalities.

Methods: A national prospective survey was conducted in 11 early-phase clinical trial centers (CLIP) certified by the French National Cancer Institute.

Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy.

Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients' quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation.

Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab.

Gemcitabine plus platinum-based chemotherapy in combination with bevacizumab for kidney metastatic collecting duct and medullary carcinomas: Results of a prospective phase II trial (BEVABEL-GETUG/AFU24).

Background: Renal medullary carcinoma (RMC) and collecting duct carcinoma (CDC) are rare entities with a poor outcome. First-line metastatic treatment is based on gemcitabine + platinum chemotherapy (GC) regimen but retrospective data suggest enhanced anti-tumour activity with the addition of bevacizumab. Therefore, we performed a prospective assessment of the safety and efficacy of GC + bevacizumab in metastatic RMC/CDC.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma.

Baseline quality of life and chemotherapy toxicities in patients with early breast cancer.

Background: The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose-reductions (CDRs) or postchemotherapy-toxicities (PCTs).

Methods: In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30, and two endpoints-CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models.

The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer.

Objective: Identifying new modifiable prognostic markers is important for ovarian cancer (OC). Low parasympathic activity is associated with inflammation, oxidative stress and sympathetic nervous system activation. Previous studies reported that low vagal nerve activity, measured by low heart rate variability (HRV), may predict poor cancer prognosis.

TALASUR trial: a single arm phase II trial assessing efficacy and safety of TALazoparib and Avelumab as maintenance therapy in platinum-Sensitive metastatic or locally advanced URothelial carcinoma.

Background: Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients with advanced UC.

Ribosome biogenesis-based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group.

Resistance of advanced hormone-dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) and Anastrozole (A, aromatase inhibitor) improves the progression-free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome.

How to improve adherence of guidelines for localized testicular cancer surveillance: A Delphi consensus study.

Stage-I testicular germ-cell tumor (TGCT) has excellent cure rates. Surveillance is fully included in patient's management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, mainly concerning imaging frequency and long-term follow-up.

Chemotherapy following immune checkpoint inhibitors in patients with locally advanced or metastatic urothelial carcinoma.

Background: Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC).

Methods: In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020.

Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial.

Background: Immune checkpoint inhibitors (ICI) targeting Programmed death-1 (PD-1) have shown their efficacy in advanced MSI/dMMR (microsatellite instability/deficient mismatch repair) tumors. The MSI/dMMR status predicts clinical response to ICI. The promising results evaluating ICI in localized MSI/dMMR tumors in neoadjuvant setting need to be confirmed in MSI/dMMR solid tumors.

Access to early-phase clinical trials in older patients with cancer in France: the EGALICAN-2 study.

Background: Access to clinical trials and especially early-phase trials (ECT) is an important issue in geriatric oncology. As cancer can be considered an age-related disease because the incidence of most cancers increases with age, new drugs should also be evaluated in older patients to assess their safety and efficacy. The EGALICAN-2 study was primarily designed to identify social and/or regional inequalities regarding access to ECT.

Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer According to Somatic Damage DNA Repair Gene Alterations.

(1) Background: In literature, approximately 20% of mCRPC present somatic DNA damage repair (DDR) gene mutations, and their relationship with response to standard therapies in mCRPC is not well understood. The objective was to evaluate outcomes of mCRPC patients treated with standard therapies according to somatic DDR status. (2) Methods: Eighty-three patients were recruited at Caen Cancer Center (France).

REchallenge of NIVOlumab (RENIVO) or Nivolumab-Ipilimumab in Metastatic Renal Cell Carcinoma: An Ambispective Multicenter Study.

Introduction: Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors.

Impact of the timing of tumor assessments on median progression-free survival in clinical trials in advanced cancer patients.

Background: Survival-based surrogate endpoints such as progression-free survival (PFS) are commonly used in oncology clinical trials. The evaluation-time bias in the assessment of median disease progression in randomized trials has been suggested by several simulation studies, but never demonstrated in the clinic. We aimed to demonstrate the existence of potential evaluation-time bias by assessing the impact of the timing of tumor assessments on median PFS from control arms without any active treatment of randomized controlled trials involving advanced cancer patients.

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis.

Unlabelled: Randomized clinical trials (RCTs) of anticancer drugs without active comparators in patients who have exhausted standard of care treatment options are debated. We aimed to quantify the safety and the efficacy of anticancer drugs in advanced cancer patients who have exhausted standard of care treatments from RCTs without active comparators. This systematic review and meta-analysis was conducted according to preferred reporting Items for systematic review and Meta-Analyses (PRISMA) guidelines (CRD42021243968).

CABOCOL-01 trial: a single-arm phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure.

Background: Cervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor.

Identifying patients eligible for PARP inhibitor treatment: from NGS-based tests to 3D functional assays.

Within the past few years, poly (ADP-ribose) polymerase inhibitors (PARPi) have been added to the standard of care for cancer patients, mainly for those exhibiting specific genomic alterations in the homologous recombination (HR) pathway. Until now, patients who are eligible to receive PARPi have been identified using next-generation sequencing (NGS) of gene panels. However, NGS analyses do have some limitations, with a subset of patients with negative NGS-based results can exhibit a clinical benefit, responding positively to PARPi, despite the failure to detect dynamic and predictive biomarkers such as mutated BRCA1/2 genes.

Predicting tumor response and outcome of second-look surgery with F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer.

Background: This ancillary study aimed to evaluate F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery.

Materials And Methods: Central review was performed by two readers blinded to the received treatment and to the patients' outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease).