Customized Adjuvant Phase II Trial in Patients With Non–Small-Cell Lung Cancer: IFCT-0801 TASTE
Mené sur 150 patients ayant subi une résection complète d'un cancer du poumon non à petites cellules de stade II ou IIIA, cet essai francais de phase II évalue la faisabilité d'une chimiothérapie adjuvante personnalisée (cisplatine-pemetrexed et, éventuellement, erlotinib) basée sur l'analyse des mutations du gène EGFR
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.