Phase II randomized trial of afatinib with or without cetuximab as first-line treatment for EGFR mutated non-small cell lung cancer (NSCLC) patients (IFCT-1503 ACE-Lung).

Abstract

9079 Background: First-line treatment of metastatic EGFR-mutated NSCLC relies on EGFR-TKIs. However, all patients (pts) eventually develop progression. Dual inhibition of EGFR with afatinib (A), an irreversible pan-erbB TKI, and cetuximab (C), an EGFR monoclonal antibody, has shown activity in EGFR-mutated pts with acquired resistance to TKIs, regardless of the T790M status. Methods: We conducted a phase II randomized trial in advanced NSCLC pts harboring an activating EGFR mutation, who had not received prior therapy. Pts were treated with A (40 mg/d) until progression alone or with C 500 mg/m² every 2 weeks during 6 months (mos) (beginning at D15 at 250 mg/m²). Primary endpoint was time-to-treatment failure (TTF) at 9 mos for pts with del19 and L858R mutations. Secondary endpoints include safety, progression-free survival (PFS), overall survival (OS). Prospective monitoring of the T790M mutation was performed on circulating tumoral DNA (ctDNA) by digital PCR. Results: Trial was stopped early due to futility analysis after 118 pts were enrolled (59 in each arm). Baseline characteristics were balanced between the 2 arms, and especially for the types of EGFR mutation (del19, 55.9 vs 50.8%; L858R, 39 vs 40.7%; others, 5.1 vs 8.5% in AC and A arms, respectively). Treatment-related AEs of any grades were similar, although there was an excess of grade 3 AEs in the AC arm (50 vs 37.3%), but no of grade 5. The excess in grade 3-5 AEs was essentially due to cutaneous (96.6 vs 81.4%), eyes (32.8 vs 27.1%), hematological (22.4 vs 15.3%) but not to digestive toxicities (89.7 vs 98.3%). Among the 117 pts included in the efficacy analysis, 9-months TTF was 63.3% (47.5-75.6) in arm A and 65.8% (50.1-77.66) in arm AC. Median TTF was 11.1 mos (8.3-not reached [NR]) and 10.8 mos (9.2-13.7) in arms A and AC, respectively. Median PFS was 11.1 mos (8.3-NR) and 12.8 mos (9.2-13.7), respectively. Median OS was 20.8 mos (17.5-NR) and NR (17-NR), respectively. Conclusions: Efficacy of AC was similar to that of A alone. These results don’t support further evaluation of this combination in this setting. Results of ctDNA monitoring will be reported during the meeting. Clinical trial information: NCT02716311.

Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update

“…Another study used afatinib as the control arm versus afatinib with cetuximab; this study (IFCT-1503 ACE-Lung) included some patients with rarer EGFR (G719X, L861Q, and S768I) mutations, with a primary outcome of time to treatment failure (TTF) at 9 months. 16 The TTF (by 0.8 months) and PFS at 9 months (by 8.7 months) were longer with afatinib alone. The RR and 1-year survival were higher with the combination.…”

“…Abbreviations 4 Virginia Commonwealth University, Richmond, VA 5 Sidney Kimmel CCC at JHU, Baltimore, MD 6 Juravinski Cancer Centre, Hamilton, ON, Canada 7 University of Colorado School of Medicine, Denver, CO 8 Banner MDA Cancer Center, Greeley, CO 9 Affiliated Oncologists, LLC, Chicago Ridge, IL 10 Lahey Hospital and Medical Center, Burlington, MA 11 Houston Methodist Cancer Center, Houston, TX 12 William Beaumont Hospital, Royal Oak, MI 13 University of Texas Southwestern Medical Center, Dallas, TX 14 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 15 ALLIANCE For Clinical Trials in Oncology, Galva, IA 16 City of Hope, City of Duarte, CA 17 Memorial Sloan Kettering Cancer Center, New York, NY 18 Catalan Institute of Oncology, Barcelona, Catalonia, Spain 19 The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted.…”

Efficacy of Afatinib in the Treatment of Patients with Non-Small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

“…The efficacy of afatinib in treating NSCLC and metastatic/recurrent HNSCC (M/R HNSCC) was reported in several randomized controlled trials (RCTs) in terms of overall survival (OS) and progression-free survival (PFS) [21][22][23][24][25][26][27][28][29][30][31][32]. Interestingly, there is a metaanalysis for the afatinib impact on survival in advanced NSCLC (6 RCTs) and M/R HNSCC (1 RCT) based on the published trials before August 2018 [33].…”