A phase III study of induction therapy with gemcitabine + carboplatin (GC) followed by either delayed vs. immediate second-line therapy with docetaxel (D) in advanced non-small cell lung cancer (NSCLC)

Abstract

7142 Background: GC is one of several active platinum-based regimens in NSCLC. Enhancing this effect with follow-on therapy, however, is less clear. The efficacy of D in the second-line setting at the time of progression is well established. Nevertheless, its role as sequential chemotherapy following a response to a platinum regimen is unclear. Treatment benefit, quality of life, and overall survival all factor into this decision. The purpose of this trial was to test the value of immediate sequential D compared with standard therapy of second-line D at the time of progression following initial therapy with GC. This abstract reports the results of the initial GC; data on immediate vs delayed D strategies will be determined by overall survival and is ongoing. Methods: Pts with Stage IIIB or IV NSCLC were enrolled (including pts with recurrent disease after primary treatment). G 1000mg/m2 was administered on day 1,8 followed by C at AUC 5.0 on day 1. After 4 cycles, non-progressers were then randomized to immediate D (75mg/m2 administered on day 1 every 3 wks) or delayed D (pts were observed until first evidence of PD). Results: 356 pts (M 61%; F 39%) have received GC of a planned 550. Median age: 65.2 yrs; Performance status 0:1:2 = 43%: 44%:13%. Clinical Stage IIIB: IV = 14%: 83%. To date, 145 have been randomized between immediate or delayed D. Primary Grade 3/4 events during GC out of 1076 cycles were neutropenia (8.1%), thrombocytopenia (7.8%), febrile neutropenia (0.5%) and anemia (3.3%); Primary nonhem Grade 3/4 events included nausea & vomiting (2%), dyspnea (1.7%) Pneumonia, rash, and alopecia occurred ≤ 0.1%. The clinical benefit rate to induction GC in 179 evaluable pts is 86% (CR 2.2%; PR 35.8%, SD= 48.6%), with a response rate of 38% (CR+PR) (95% CI: 30.9%–45.5%), PD=13.4%. Conclusions: Currently 423 pts (75% of targeted accrual) have been enrolled, this preliminary data supports the efficacy and tolerability of first-line GC in advanced NSCLC, once accrual and event endpoints have been attained, further information will be available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly, Genentech AstraZeneca, Taiho Millenium EMD Eli Lilly Eli Lilly, GlaxoSmithKline, Lilly Oncology Taiho, Member of the Speakers Bureau of Eli Lilly and Company Eli Lilly, Lilly Underwriters Trial 02099 for me in breast cancer, Participation in Clincial Trial with Eli-Lilly and Company