A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non-Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib
Mené sur 50 patients atteints d'un cancer avancé du poumon non à petites cellules ayant développé une résistance au géfitinib ou à l'erlotinib, cet essai de phase Ib/II évalue la dose maximale tolérée, l'efficacité (du point de vue du taux de réponse globale) et la toxicité d'un traitement combinant afatinib et nimotuzumab
Purpose: In this phase Ib/II study, we aimed to assess the safety and efficacy of afatinib (A) plus nimotuzumab (N) in advanced non-small cell lung cancer (NSCLC) patients with acquired resistance to gefitinib or erlotinib. Experimental Design: In phase Ib stage, patients received A (40mg or 30mg once daily) plus N (100mg or 200mg once weekly) for 28-day cycles to determine the recommended phase II dose (RPIID). The safety and efficacy of RPIID dose was evaluated in phase II stage. Results: In total, 50 patients were enrolled (13 to phase Ib and 37 to phase II). In the first dose-finding cohort (A 40mg plus N 100mg), one patient experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and in the subsequent cohort (A 40mg plus N 200mg), two DLTs (grade 3 diarrhea and grade 3 neutropenia) occurred in 2 out of 6 patients. Accordingly, RPIID was determined as A 40mg plus N 100mg. In 44 patients treated with RPIID, 7 (16%) patients had grade 3 toxicities; skin rash (7%), diarrhea (5%), acne (2%), and fatigue (2%). The overall response rate was 23% and the median duration of response was 4.3 months (range, 0.7-16.2 months). The median PFS and OS were 4.0 months (95% CI, 2.3-5.7 months) and 11.7 months (95% CI, 9.4-14.0 months), respectively. Conclusions: Combination treatment of afatinib and nimotuzumab demonstrated an acceptable safety profile and encouraging antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib. Larger phase III trial is warranted to confirm its efficacy and safety.