P2.02-012 Long-Term Survival of Phase II of Full-Dose Oral Vinorelbine Combined with Cisplatin & Radiotherapy in Locally Advanced NSCLC

Abstract

Chemo-radiotherapy is the standard of care for the treatment of inoperable locally advanced non-small cell lung cancer (LA-NSCLC). Cisplatin (P) plus vinorelbine is one of the chemotherapy (CT) regimens widely used concurrently with radiotherapy (RT). Since oral vinorelbine (oV) has achieved comparable results to the IV formulation, the optimal dose for the oV administration with P and concurrent RT is still being investigated. The aim of this study is to evaluate the efficacy and safety of full-dose oV combined with P and radical RT for LA-NSCLC patients (pts). Untreated pts between 18-70 years (y), with histologically proven inoperable LA-NSCLC (supraclavicular lymph node involvement excluded), V20<30%, adequate bone marrow, respiratory, hepatic and renal function, and ECOG PS0-1; received 4 cycles (cy) of oV 60 mg/m2 D1 & 8 plus P 80 mg/m2 D1, every 3 weeks, plus 2Gy/day of RT started on D1 of 2nd cy (total dose 66Gy). Primary endpoint was overall response rate (ORR) by RECIST 1.1. Secondary endpoints were: progression free survival (PFS), overall survival (OS) & safety profile. To guarantee a type-1 (□) error (one side) no greater than 0.05 and a type II (β) error 0.1 for the primary endpoint, a sample size of 45 eligible pts was planned. EudraCT 2009-010436-17. Forty-eight pts were included between 02/2010-12/2011. Median age 61y [34-72], male 90%, PS1 58%; smokers 52%; squamous 63%; stage IIIB 54%. Main G3-4 toxicities (% cy) were: neutropenia 33%, febrile neutropenia 14.6%, anemia 12.5%, thrombocytopenia 16.6%, & esophagitis 12.5%. Two treatment-related deaths during the 1st cy. RT was administered to 87.5% of pts; 7.1% received less than 60Gy and 23.8% had delays due to adverse events. The ORR was 77.3% (2 complete responses). With a median follow-up of 28.2 months (m) [0.5-70.6], 33 pts (68.8%) have progressed and 32 (66.7%) have died. Median PFS and OS were 11.8m (CI95% 7.2-16.5) and 29.8m (CI95% 21.4-38.1), respectively. PFS at 1y was 48.8% pts (CI95% 33.9-63.7%). OS at 1 and 2y were 72.7% (CI95% 60-85.4%) and 57.3% (CI95% 43-71.6%), respectively. This long-term analysis confirms the good efficacy results of the administration of full doses of oral vinorelbine combined with cisplatin and concurrent RT in patients with LA-NSCLC.