Marie Wislez1, Fabrice Barlesi, Benjamin Besse, Julien Mazières, Patrick Merle, Jacques Cadranel, Clarisse Audigier-Valette, Denis Moro-Sibilot, Laure Gautier-Felizot, François Goupil, Aldo Renault, Elisabeth Quoix, Pierre-Jean Souquet, Anne Madroszyck, Romain Corre, David Pérol, Franck Morin, Gérard Zalcman, Jean-Charles Soria. 1. Marie Wislez and Jacques Cadranel, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris; Franck Morin, Intergroupe Francophone de Cancérologie Thoracique, Paris; Fabrice Barlesi, Aix Marseille University, Assistance Publique des Hôpitaux de Marseille; Anne Madroszyck, Institut Paoli Calmettes, Marseille; Benjamin Besse and Jean-Charles Soria, Institut Gustave Roussy, Villejuif; Julien Mazières, Hôpital Larrey, Toulouse; Patrick Merle, Centre Hospitalier Universitaire (CHU) de Clermont-Ferrand, Clermont-Ferrand; Clarisse Audigier-Valette, Hôpital Sainte Musse, Toulon; Denis Moro-Sibilot, CHU de Grenoble, Grenoble; Laure Gautier-Felizot, Centre Hospitalier de Dax, Dax; François Goupil, Centre Hospitalier du Mans, Le Mans; Aldo Renault, Centre Hospitalier de Pau, Pau; Elisabeth Quoix, Nouvel Hôpital Strasbourg, Strasbourg; Pierre-Jean Souquet, Centre Hospitalier Lyon-Sud; David Pérol, Centre Léon Bérard, Lyon; Romain Corre, Hôpital Pontchaillou, Rennes; and Gérard Zalcman, CHU Caen, Caen, France.
Abstract
PURPOSE:Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non-small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response. PATIENTS AND METHODS: This prospective randomized phase II trial enrolled 150 patients with completely resected non-squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution. RESULTS: In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated toCP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%. CONCLUSION: The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.
RCT Entities:
PURPOSE: Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non-small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response. PATIENTS AND METHODS: This prospective randomized phase II trial enrolled 150 patients with completely resected non-squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution. RESULTS: In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated to CP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%. CONCLUSION: The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.
Authors: Nathan A Pennell; Joel W Neal; Jamie E Chaft; Christopher G Azzoli; Pasi A Jänne; Ramaswamy Govindan; Tracey L Evans; Daniel B Costa; Heather A Wakelee; Rebecca S Heist; Marc A Shapiro; Alona Muzikansky; Sudish Murthy; Michael Lanuti; Valerie W Rusch; Mark G Kris; Lecia V Sequist Journal: J Clin Oncol Date: 2018-11-16 Impact factor: 44.544