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Immunotherapy with checkpoint inhibitors has become the cornerstone of systemic treatment for non-oncogene addicted non-small-cell lung cancer. Despite its pivotal role, a significant proportion of patients-approximately 70-85%-either exhibit primary resistance to PD-1 blockade or develop acquired resistance following an initial benefit, even in combination with chemotherapy and/or anti-CTLA-4 agents. The phenomenon of primary and acquired resistance to immunotherapy represents a critical clinical challenge, largely based on our incomplete understanding of the mechanisms of action of immunotherapy, and the resulting lack of accurate predictive biomarkers. Here, we review the definitions and explore the proposed mechanisms of primary and acquired resistance, including those related to the tumor microenvironment, systemic factors, and intrinsic tumor characteristics. We also discuss translational data on adaptive changes within tumor cells and the immune infiltrate following exposure to checkpoint inhibitors. Lastly, we offer a comprehensive overview of current and emerging therapeutic strategies designed to prevent primary resistance and counteract acquired resistance., Competing Interests: Declarations. Funding: Open access funding provided by University of Geneva. No external funding was used in the preparation of this manuscript. Conflicts of interest: A.M. received financial support to attend scientific meetings for registration travel and accommodation from Johnson&Johnson, Roche and PharmaMar. M.B. received financial support to attend scientific meetings for registration travel and accommodation from Bayer, MSD, AstraZeneca and PharmaMar. D.F. received financial support to attend scientific meetings for registration travel and accommodation from MSD. A.A. declares receiving institutional fees from the following companies: BMS, AstraZeneca, Boehringer-Ingelheim, Roche, MSD, Pfizer, Eli Lilly, Merck, PharmaMar, and Novartis. A.A. also reports participation in the Speaker Bureau for Eli Lilly and AstraZeneca. M.W. and F.K. declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Ethics approval, consent to participate, consent for publication, availability of data and material, code availability: Not applicable., (© 2025. The Author(s).)

Dermatologic and rheumatologic toxicities are frequent adverse events during treatment with immune checkpoint inhibitors in oncology. Timely identification of these events and the referral to the oncologist or dermatologist are important in daily practice, such an organ damage involvements can be severe and sometimes life-threatening. The diagnosis and management of cutaneous toxicities, such as maculopapular rash and bullous dermatitis in particular, must be based on the body surface affected by skin lesions. Corticosteroids are basic treatment in moderate to severe cases. Rheumatologic toxicities are rarer and more heterogeneous, and they are often underestimated. They can occur in the absence of autoantibodies, and myositis can be life-threatening.

Background: Using US population-level data, it has been suggested that novel treatment advances, particularly targeted therapies, have contributed to a sharp fall in NSCLC mortality. Switzerland is a high-income country, with a universal, highly performant health care system, easy access to novel drugs but with different dynamics concerning the smoking epidemic than the US., Methods: We use population-based data from Swiss cancer registries to analyze the trends in incidence, mortality and survival and relate them to recent drug approvals., Results: The incidence of NSCLC and SCLC was stable from 1980 to 2018. We noted an important difference between sexes, with an important decrease in men and increase in women, especially for NSCLC. 1-y and 5-y survival have improved for NSCLC between 2004 and 2008 and 2014-2018., Conclusion: These findings should be regarded as the results of a multifactorial improvement in care and it is difficult for us to pinpoint a unique cause explaining the reduction in mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung cancer is the leading cause of cancer mortality worldwide. Immunotherapy has demonstrated clinically significant benefit for non-small-cell lung cancer, but innate (primary) or acquired resistance remains a challenge. Criteria for a uniform clinical definition of acquired resistance have been recently proposed in order to harmonize the design of future clinical trials. Several mechanisms of resistance are now well-described, including the lack of tumor antigens, defective antigen presentation, modulation of critical cellular pathways, epigenetic changes, and changes in the tumor microenvironment. Host-related factors, such as the microbiome and the state of immunity, have also been examined. New compounds and treatment strategies are being developed to target these mechanisms with the goal of maximizing the benefit derived from immunotherapy. Here we review the definitions of resistance to immunotherapy, examine its underlying mechanisms and potential corresponding treatment strategies. We focus on recently published clinical trials and trials that are expected to deliver results soon. Finally, we gather insights from recent preclinical discoveries that may translate to clinical application in the future., Competing Interests: AF: Advisory board with Roche, Pfizer, Astellas, AstraZeneca, MSD, Sanofi, Novartis and BMS. AA: Advisory board: MSD Oncology, Roche, Takeada, Pfizer, Bristol-Myers Squibb, AstraZeneca, Eli-Lilly, Roche. Speaker Bureau: Eli-Lilly, AstraZeneca.PT: Advisory board with Astellas, Bayer, BMS, Ipsen, Janssen-Cilag, Merck, MSD, Pfizer, Roche and Sanofi. Travel and conference expenses from Lilly, Janssen-Cilag and Sanofi. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Frisone, Friedlaender, Addeo and Tsantoulis.)

Purpose of Review: There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer., Recent Findings: Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more "targeted" adjuvant treatment., (© 2021. The Author(s).)

BRAF is a rare targetable mutation in non-small-cell lung cancer (NSCLC). Emerging evidence underlines that, rather than a single point mutation, BRAF genes present with a wide array of mutations, essentially in lung adenocarcinoma. Different BRAF mutations have divergent clinical and therapeutic implications, with a particular distinction between V600E and non-V600E mutations. The latter are at least as frequent in NSCLC as V600E, but lack any proven targeted therapy. In this paper, we briefly review the current literature and provide an update of scientific knowledge about different types of BRAF mutations in NSCLC., Competing Interests: Declaration of Competing Interest Alfredo Addeo has has received compensation from Bristol-Myers Squibb, AstraZeneca, Merck Sharpe & Dohme, Takeda, Pfizer, Roche and Boehringer Ingelheim for participating on advisory boards. Alex Friedlaender has received compensation from Roche, Pfizer, Astellas and Bristol-Myers Squibb for service as a consultant. Daniele Frisone has no conflicts of interest. Giuseppe Banna reported receiving personal fees from Merck Sharp & Dohme, Boehringer Ingelheim, Janssen-Cilag, and Roche outside the submitted work. Umberto Malapelle Umberto Malapelle has received personal fees from Boehringer Ingelheim, Roche, MSD, Amgen, Merck, and Astrazeneca., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from CDKN2A down-regulation, CCNE1 amplification, CCND1/2 amplification, and RB1 loss. However, bi-allelic CDKN2A mutation or homozygous deletion is a very rare event, concerning less than 5% of patients.Initial trials with palbociclib in serous ovarian cancer have shown very modest benefit in unselected patient populations, thus underlining the need for a biomarker predicting response. We report the case of a heavily pre-treated patient with a serous ovarian tumor harboring a homozygous deletion of the CDKN2A gene that derived significant, prolonged clinical benefit from palbociclib, a CDK4/6 oral inhibitor, with letrozole. Treatment with palbociclib and letrozole started on February 2018, with an ongoing response after 12 months.In conclusion, homozygous CDKN2A deletion is rare and could be used to predict response to CDK4/6 inhibitors in association with other genomic features. We encourage further trials in this direction.

Daily medical practice triggers reflexes in the use of drugs which must nevertheless always be adapted to new knowledge. Physician assistants and residents in the clinical ward of Internal Medicine of Sion Hospital summarize six recently published clinical treatments to which primary care physicians or in hospital-based internal medicine have to pay a particular attention. Quinolones are widely used but associated with QT interval widening, morphine delays and attenuate ticagrelor action in patients with myocardial infarction, evolocumab, a monoclonal antibody impact in reducing lipids and cardiovascular events, impact of statins on influenza vaccine effectiveness, vitamin D treatment for the prevention of functional decline, high dose dexamethasone for the treatment of immune thrombocytopenia., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.