Cancer science
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Multicenter Study
An Individualized Model for Predicting COVID-19 Deterioration in Patients with Cancer: A Multicenter Retrospective Study.
The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. ⋯ The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.
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Randomized Controlled Trial Multicenter Study
First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset.
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD-L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. ⋯ Immune-mediated adverse events and infusion reactions occurred in 11 pembrolizumab-treated patients (52%) and four chemotherapy-treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFR/ALK alterations and a PD-L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
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Multicenter Study
Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts.
Capmatinib is an oral, ATP-competitive, and highly potent, type 1b MET inhibitor. Herein, we report phase 1 dose-escalation results for capmatinib in advanced MET-positive solid tumor patients and dose expansion in advanced non-lung tumors. Capmatinib was well tolerated with a manageable safety profile across all explored doses. ⋯ Incidence of high-level MET GCN (GCN ≥6) and MET-overexpressing (immunohistochemistry 3+) tumors in the expansion cohorts was 8% and 13%, respectively; no MET mutations were observed. Thus, the recommended phase 2 dose (RP2D) of capmatinib was 600 mg bid capsule/400 mg bid tablet. Capmatinib was well tolerated and showed antitumor activity and acceptable safety profile at the RP2D. (ClinicalTrials.gov Identifier: NCT01324479).
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Randomized Controlled Trial Multicenter Study Comparative Study
Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.
The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. ⋯ Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).
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Randomized Controlled Trial Multicenter Study
Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer: A pooled subgroup analysis.
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. ⋯ Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.