INTRODUCTION: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS: Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION: Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

• Klíčová slova
• Adverse event, Edema, MET inhibitor, Nausea, Non–small cell lung cancer,
• MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• exony genetika   MeSH
• hypoalbuminemie farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kreatinin terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * farmakoterapie   genetika   MeSH
• nauzea chemicky indukované   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   MeSH
• piperidiny škodlivé účinky   MeSH
• pleurální výpotek MeSH
• průjem MeSH
• pyridaziny škodlivé účinky   MeSH
• pyrimidiny škodlivé účinky   MeSH
• senioři MeSH
• zvracení chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory proteinkinas * MeSH
• kreatinin MeSH
• piperidiny MeSH
• pyridaziny MeSH
• pyrimidiny MeSH
• tepotinib MeSH Prohlížeč

• Klíčová slova
• 5′ Fusion partner, Gene fusion, SCID-Beige mice, Survival, Targeted therapy,
• MeSH
• adenokarcinom plic diagnóza   genetika   MeSH
• anaplastická lymfomová kináza genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• myši SCID MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory plic diagnóza   genetika   MeSH
• proteiny nervové tkáně genetika   MeSH
• proteiny vázající kalmodulin genetika   MeSH
• staging nádorů MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anaplastická lymfomová kináza MeSH
• fúzní onkogenní proteiny MeSH
• membránové proteiny MeSH
• proteiny nervové tkáně MeSH
• proteiny vázající kalmodulin MeSH
• STRN protein, human MeSH Prohlížeč

BACKGROUND: The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non-small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC. PATIENTS AND METHODS: Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 (arm A) or oral vinorelbine 80 mg/m(2) on days 1 and 8 (first cycle 60 mg/m(2)) and cisplatin 80 mg/m(2) on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine. RESULTS: Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm. CONCLUSION: Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.

• Klíčová slova
• Advanced non–small-cell lung cancer, Chemotherapy, Nonsquamous histologic subtype, Pemetrexed, Vinorelbine,
• MeSH
• analýza přežití MeSH
• aplikace orální MeSH
• cisplatina aplikace a dávkování   škodlivé účinky   MeSH
• glutamáty aplikace a dávkování   škodlivé účinky   MeSH
• guanin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   MeSH
• neutropenie etiologie   MeSH
• pemetrexed MeSH
• progrese nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• staging nádorů MeSH
• vinblastin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• vinorelbin MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• cisplatina MeSH
• glutamáty MeSH
• guanin MeSH
• pemetrexed MeSH
• vinblastin MeSH
• vinorelbin MeSH