Cisplatin (CDDP) plus vinorelbine (VRB) as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC): Molecular correlates

Abstract

7692 Background: The combination of cisplatin plus vinorelbine is a reference regimen as first-line therapy in advanced NSCLC. The correlation between predictive genetic markers and clinical endpoints may improve the prediction of treatment success and thereby the tailoring of chemotherapy. In this trial, predictive genetic markers of response to CDDP/VRB were examined in genomic DNA and cDNA derived from tumors and circulating tumors. Methods: 238 chemonaive p with stage IIIB (pleural effusion or supraclavicular lymph nodes)- IV or recurrent NSCLC were accrued at 35 sites between April 2004 and January 2006. Treatment consisted of CDDP 75 mg/m2 IV day 1 plus VRB 25 mg/m2 IV or 60–80 mg/m2 oral, days 1, 8 every 21 days. DNA samples were collected from primary tumors for the assessment of microtubule associated protein 4 (MAP4) and from serum for the checkpoint forkhead-associated and ring finger (CHFR) methylation. Results: Data on 198 p is available. Median age 62 years (38–80); males: 83.8%; smokers: 77.8%; PS 0–1: 95.3%; adenocarcinoma, 48.9% / squamous, 32.8%; stage IIIB: 16.7%, IV: 83.3%. Median cycles: 4 (1–12). Hematological toxicities (%p): grade 3/4 neutropenia, 9.6%/7.6%; grade 3/4 thrombocytopenia, 0.5%/0.5%; grade 3 anemia, 2%. Febrile neutropenia appeared in 14 cycles / 10 p (1.8%/5,1%). Non-hematological toxicities (%p): pulmonary grade 3/4, 3.0%/2.5%; nausea/vomiting grade 3/4, 7.6%/0.5%; asthenia grade 3, 13.2%; pain grade 3, 6.6%; infection grade 3, 4.1%; neurotoxicity grade 3, 0.5%. Efficacy in evaluable population: CR, 2.3%; PR, 30.8%; ORR, 33.1% (95% CI, 26.1% to 40.2%); SD, 39.7%. With a median follow up of 6.7 months, median survival for the whole population was 9 months (m), progression free survival 5.07 m, event free survival 4.8 m, 1-year survival 39.9%. Conclusions: The tolerability, efficacy and survival results of this trial confirm that CDDP/VRB is effective as first-line therapy, presenting a favorable toxicity profile in p with advanced NSCLC. Complete data on genetic markers will be presented. No significant financial relationships to disclose.