RESUMO
BACKGROUND/AIM: KRAS mutation is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC). It is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about their efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. PATIENTS AND METHODS: All stage IV NSCLC patients treated in our institution from January 2016 to December 2017 with immunotherapy were included in our analysis. We collected the status of KRAS and other mutations, as well as the type of ICI administered. We assessed four clinical outcomes: i) disease control rate (DCR), ii) partial response (PR), iii) progression-free survival (PFS) and iv) overall survival (OS). RESULTS: A total of 45 patients were initially identified but 7 were excluded due to insufficient clinical data, so 38 were included in the end. In the KRAS wild-type cohort, the DCR was 59% with 49% PR, while the PFS was 8.4 months and OS 16.8 months. Among KRAS mutated patients, results were more favourable, the DCR was 81%, with 62% PR. PFS was 13.6 months and OS was 18.5 months. The median follow-up was 24 months (17 to 34 months) and 7 patients were still on treatment at the time of analysis. CONCLUSION: Our data suggest that KRAS mutation is predictive of a superior response to immunotherapy. Furthermore, the lack of response of STK11 and KRAS co-mutated NSCLC patients to ICIs, is indeed negated by an additional TP53 mutation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Quinases Proteína-Quinases Ativadas por AMP , Adulto , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genéticaRESUMO
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.