Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation
Journal
Journal of Thoracic Oncology
Journal Volume
14
Journal Issue
3
Pages
553-559
Date Issued
2019
Author(s)
Gadgeel S.M
Sequist L.V
Wu C.-L
Papadimitrakopoulou V.A
Su W.-C
Fiore J
Saraf S
Raftopoulos H
Patnaik A.
Abstract
Introduction: Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674). Methods: Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose. Results: Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose-limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment-related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater. Conclusions: Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti-EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy outcomes. ? 2019 International Association for the Study of Lung Cancer
Subjects
Combination therapy; Erlotinib; Gefitinib; NSCLC; Pembrolizumab
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; epidermal growth factor receptor; erlotinib; gefitinib; pembrolizumab; prednisone; programmed death 1 ligand 1; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; erlotinib; gefitinib; monoclonal antibody; pembrolizumab; acne; adult; advanced cancer; aged; arthralgia; Article; autoimmune hepatitis; bacterial skin disease; cancer combination chemotherapy; cancer staging; chemosensitization; clinical article; clinical assessment tool; cohort analysis; colitis; decreased appetite; dermatitis; diarrhea; dizziness; drug efficacy; drug safety; drug withdrawal; dry eye; dry skin; EGFR gene; fatigue; feasibility study; female; fever; gene mutation; hepatitis; human; human cell; human tissue; hypothyroidism; ingrown nail; maculopapular rash; male; monotherapy; multicenter study; nausea; non small cell lung cancer; open study; pharmacogenetics; phase 1 clinical trial; phase 2 clinical trial; pneumonia; priority journal; protein expression; pruritus; rash; recommended drug dose; Response Evaluation Criteria in Solid Tumors version 1.1; side effect; skin manifestation; skin toxicity; treatment response; uveitis; clinical trial; follow up; genetics; lung tumor; middle aged; mutation; non small cell lung cancer; pathology; prognosis; survival rate; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cohort Studies; ErbB Receptors; Erlotinib Hydrochloride; Female; Follow-Up Studies; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Prognosis; Survival Rate
Publisher
Elsevier Inc
Type
journal article