Final results from a Phase II study of pemetrexed and cisplatin with concurrent thoracic radiation after Pem-Cis induction in patients with unresectable locally advanced non-squamous non-small cell lung cancer (NSCLC)
Mené sur 90 patients atteints d'un cancer du poumon non épidermoïde, non résécable et non à petites cellules de stade III (âge médian : 61 ans ; 43 % de femmes), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de survie sans progression à 1 an, et la toxicité d'une chimiothérapie d'induction par pémétrexed-cisplatine suivie d'un traitement combinant de manière concomitante une chimiothérapie par pémétrexed-cisplatine et une radiothérapie
Objectives : This single-arm multicenter Phase II study investigated the efficacy and safety of pemetrexed (Pem) and cisplatin (Cis) induction chemotherapy (CT) followed by full-dose Pem-Cis plus concurrent radiotherapy (RT) in patients with locally-advanced non-squamous NSCLC. Materials and Methods : Patients with unresectable Stage III non-squamous NSCLC received two 21-day cycles of Pem 500 mg/m2 (vitamin/folic acid supplementation and dexamethasone prophylaxis per Pem-label) + Cis 75 mg/m2 on Day 1. Eligible patients who had not progressed continued with 2 further cycles of full-dose Pem-Cis plus concurrent RT (2 Gy/fraction, 5d/wk, 66 Gy total). Primary endpoint was the 1-year progression-free survival (PFS) rate. Results : Of 90 patients enrolled (all treated; median age 61yrs, male/female 57%/43%, ECOG performance status 0/1 66%/34%, adenocarcinoma 90%, Stage III 36%/62%), 75 (83%) completed induction CT and started concurrent CT + RT. 64(71%) patients received all 4 CT cycles and an RT dose ≥60 Gy. The 1-year PFS rate was 51.3% (95%CI: 42.0,60.5). Median PFS was 10.6 months (95%CI: 8.6,17.3), median OS was 26.2 months (95%CI: 16.7,not estimable). One patient died from enteritis (treatment-related) during Cycle 4. Four patients discontinued due to treatment-related adverse events, 1 on induction CT (renal failure), 3 on concurrent CT + RT (1 hypoacusis, 2 acute esophagitis). During induction CT, 18.9% of patients reported Grade 3/4 CTCAEs, only neutropenia (2.2%) and syncope (2.2%) were reported by >1 patient. During concurrent CT + RT, 41.3% of patients reported G3/4 CTCAEs, mainly esophagitis (12.0%), neutropenia (10.7%), and leukopenia (9.3%). Conclusion : In this study of Pem-Cis induction CT followed by full-dose Pem-Cis with concurrent RT, median PFS was 10.6 months and toxicity was manageable, in line with previous data on Pem-Cis plus RT.