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International audience; Introduction: Advanced non-small-cell lung cancers with EGFR mutation belong to the models of solid tumors which revealed the concept of oncogene addiction. For that reason, first, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are the major anti-cancer drugs used in this indication. Translational research is currently focused on induced mechanisms of resistance and aims to define the best first therapeutic option and the best multiline strategy.Areas covered: EGFR TKIs, alone or in combination, i.e. anti-angiogenic drugs or chemotherapy, have demonstrated their ability to improve median PFS and OS in large randomized phase 3 trials. All these combinations, now available in first-line for EGFR mutated advanced NSLC, need to integrate multiple factors like patients characteristics (age, co-morbidities, eligibility to platinum-based chemotherapy), presence of brain metastasis at diagnosis, and type of EGFR mutation. This review has 2 aims: (1) to discuss the current knowledge of therapies available in non pre-treated EGFR-mutated NSCLC; (2) to propose the best therapeutic option according to multiple parameters, either clinical or biological.Expert commentary: In 2020, we can affirm that osimertinib the first choice for patients with EGFR-mutated NSCLC. However, this has to be balanced with patient characteristics, type of EGFR mutation and new therapeutic options.

Background Immune checkpoint inhibitor (ICPi) rechallenge could represent an attractive option in non–small-cell lung cancer (NSCLC), yet no sufficient data supporting this strategy are available. This retrospective observational multicenter national study explored the efficacy of anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) rechallenge in advanced NSCLC patients, looking for potential clinical features associated with greater outcomes. Patients and Methods We retrospectively collected data from 144 advanced NSCLC patients whose disease was rechallenged with ICPis after ≥ 12 weeks of discontinuation. The progression-free survival (PFS) and overall survival (OS) were calculated from first or second ICPi initiation to disease progression (PFS1 and PFSR, respectively), death, or last follow-up (OS1, OSR), respectively. Results The median (interquartile range) age was 63 (58-70) years. Most patients were male (67%) and smokers (87%). Most had adenocarcinomas (62%) and/or stage IV disease at diagnosis (66%). The best response at rechallenge was not associated with that under the first ICPi (P = 1.10−1). The median (95% confidence interval) PFS1 and PFSR were 13 (10-16.5) and 4.4 (3-6.5) months, respectively. The median (95% confidence interval) OS1 and OSR were 3.3 (2.9-3.9) and 1.5 (1.0-2.1) years, respectively. Longer PFSR and OSR were found in patients discontinuing first ICPi because of toxicity or clinical decision, those not receiving systemic treatment between the two ICPis, and those with good Eastern Cooperative Oncology Group performance status at rechallenge. Only performance status proved to affect outcomes at multivariate analysis. Conclusion Patients discontinuing first ICPi because of toxicity or clinical decision, those able to maintain a treatment-free period, and those with good performance status may be potential candidates for rechallenge.

International audience; Introduction: Colorectal cancer (CRC) is one of the most frequent and lethal cancers in the world, and therapies are still insufficient. Immune checkpoint inhibitors (ICI) in metastatic CRC (mCRC) have not revolutionized treatment to the extent that they have in melanoma or renal carcinoma. Their use is limited to a molecular niche of mCRC with microsatellite instability (MSI). This review summarizes clinical data published with pembrolizumab in mCRC and also tries to identify potential new strategies. Areas covered: This paper focuses on pembrolizumab in mCRC. We screened all trials on PubMed and ClinicalTrials.gov and describe the most significant ones in our opinion. Expert opinion: Pembrolizumab seems to be effective in tumors with MSI-high status. It defines a new horizon for therapeutic strategy called 'agnostic' medicine. For microsatellite stable (MSS) colorectal cancers, the future challenge will be to successfully redraw the immune microenvironment to make it immunogenic with new therapeutic combinations, including ICI