Side Effects of Cancer Immunotherapies: Dermatologic and Rheumatologic Toxicities.

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.

Trends in incidence and mortality of lung cancer in Switzerland: Possible explanations and open questions.

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.

The Landscape of Immunotherapy Resistance in NSCLC.

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.

The Role and Impact of Minimal Residual Disease in NSCLC.

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.

A BRAF new world.

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.

Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.

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.

[New therapeutics]. / Nouvelles thérapeutiques.

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.

La pratique médicale quotidienne suscite des réflexes dans l'utilisation de médicaments qui doivent sans cesse être adaptés aux nouvelles connaissances. Les médecins du Service de médecine interne de Sion résument six publications sur des traitements auxquels le praticien ambulatoire ou hospitalier doit porter une attention particulière. L'effet des quinolones sur l'intervalle QT, l'administration concomitante de morphine et de ticagrélor en cas de syndrome coronarien aigu, la place d'un anticorps monoclonal pour abaisser le taux de cholestérol, l'impact des statines sur l'efficacité vaccinale, la rôle de la vitamine D à haute dose pour ralentir le déclin de la performance physique, le stéroïde de choix en cas de thrombopénie auto-immune.