New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab

The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naïve metastatic NSCLC with $50$1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy. In 2017, it also authorized the first-line combination of pembrolizumab and carboplatin-pemetrexed chemotherapy without selection based on PDL1 expression, but European health authorities are still waiting for the results of a Phase III trial. In this review, the clinical results of published and ongoing studies evaluating pembrolizumab for advanced NSCLC are analyzed and the potential role of PDL1 as a factor predictive of overall responses addressed

Management of patients with synchronous head-and-neck and lung cancers: SYNCHRON GFPC 15-01 study

Few data have been published on the management of patients with synchronous head-and-neck cancer (HNC) and lung cancer (LC). This observational study was undertaken to describe the management of these patients in multiple centers

ICU admission for solid cancer patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. Methods: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. Results: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered “likely” associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2–3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13–18.90, and OR = 3.66, 95% CI 1.33–10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19–9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission “likely” related to irAE. Three patients were subsequently treated with immunosuppressants. Conclusion: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Resistance mechanisms to osimertinib in EGFR-mutated advanced non-small-cell lung cancer: A multicentric retrospective French study

International audienceObjectives: The understanding of histo-molecular mechanisms associated with resistance to osimertinib is a critical step to define the optimal treatment strategy in advanced EGFR-mutated Non-Small-Cell-Lung-Cancer (NSCLC).Materials and methods: We performed a multicentric retrospective analysis on a cohort of consecutive patients treated with osimertinib for an advanced EGFR-mutated NSCLC and collected histo-molecular data from plasma and tumor samples at the time of progression. Next-generation sequencing (NGS) was performed for all samples. Best Overall Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) and data on treatment post-progression efficacy were also collected.Results: Two-hundred and twenty-six patients were included from 9 Academic French Hospitals between April 2015-October 2018. Osimertinib was given in second-line or more in 219 patients (97%). Best ORR was 52% and best central nervous system ORR was 56%. Median PFS and OS were 9.5 months (IQR 4.0-17.2) and 24 months (IQR 12.4-NR) respectively. At the time of analysis, 150 patients (66%) had tumor progression. Among them, 73 contributive samples (56 tumor biopsies) were available. The most frequent molecular alterations were C797S mutation (n = 9 (13%)) and MET amplification (n = 8 (11%)). Histologic transformation occurred in 5 patients (9% of tumor biopsies). In T790M + NSCLC, loss of T790 M occurred in 68% of cases. Median PFS and OS with treatment beyond progression were 6.0 months (IQR 2.0-10.4) and 15.1 months (IQR 6.7-NR) respectively and longer in case of osimertinib continuation beyond progression.Conclusion: We confirmed the efficacy of osimertinib in patients with advanced EGFR mutation positive NSCLC. At progression, the most frequent molecular alterations were MET amplification and C797S mutation

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study

Purpose: To study prevalence of targeted therapy (TT)-related adverse events requiring ICU admission in solid tumor patients. Methods: Retrospective multicenter study from the Nine-i research group. Adult patients who received TT for solid tumor within 3 months prior to ICU admission were included. Patients admitted for TT-related adverse event were compared to those admitted for other reasons. Results: In total, 140 patients, median age of 63 (52–69) years were included. Primary cancer site was mostly digestive (n = 27, 19%), kidney (n = 27, 19%), breast (n = 24, 17%), and lung (n = 20, 14%). Targeted therapy was anti-VEGF/VEGFR for 27% (n = 38) patients, anti-EGFR for 22% (n = 31) patients, anti-HER2 for 14% (n = 20) patients and anti-BRAF for 9% (n = 5) patients. ICU admission was related to TT adverse events for 30 (21%) patients. The most frequent complications were interstitial pneumonia (n = 7), cardiac failure (n = 5), anaphylaxis (n = 4) and bleeding (n = 4). At ICU admission, no significant difference was found between patients admitted for a TT-related adverse event and the other patients. One-month survival rate was higher in patients admitted for TT adverse event (OR = 5.733 [2.031–16.182] P < 0.001). Conclusions: Adverse events related to targeted therapy accounted for 20% of ICU admission in our population and carried a 16% one-month mortality. Outcome was associated with admission for TT related to adverse event, breast cancer and good performance status.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study

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