| Autor: |
Chau I; Gastrointestinal Units, Royal Marsden Hospital, London SM2 5PT, UK., Penel N; General Oncology Department, Medical Oncology Department, Oscar Lambret Cancer Center, 59020 Lille, France., Soriano AO; Sarah Cannon Research Institute/Florida Cancer Specialists, Englewood, FL 34223, USA., Arkenau HT; Sarah Cannon Research Institute United Kingdom and University College London, London W1G 6AD, UK., Cultrera J; Sarah Cannon Research Institute/Florida Cancer Specialists Leesburg South, Leesburg, FL 34748, USA., Santana-Davila R; Department of Medicine, University of Washington Medicine, Seattle Cancer Care Alliance, Seattle, WA 98109, USA., Calvo E; Early Phase Clinical Drug Development Program, START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, 28050 Madrid, Spain., Le Tourneau C; Department of Drug Development and Innovation, Institut Curie, 75005 Paris, France., Zender L; Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany., Bendell JC; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN 37203, USA., Mi G; Eli Lilly and Company, Indianapolis, IN 46285, USA., Gao L; Eli Lilly and Company, Indianapolis, IN 46285, USA., McNeely SC; Eli Lilly and Company, Indianapolis, IN 46285, USA., Oliveira JM; Eli Lilly and Company, New York, NY 10016, USA., Ferry D; Eli Lilly and Company, New York, NY 10016, USA., Herbst RS; Yale Cancer Center, New Haven, CT 06520, USA., Fuchs CS; Yale Cancer Center, New Haven, CT 06520, USA.; Smilow Cancer Hospital, New Haven, CT 06473, USA. |
| Abstrakt: |
Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors. |
