Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial

7005 Background: Standard therapy for unresectable stage III NSCLC includes concomitant chemoradiotherapy. In CALGB 39801, we evaluated whether the addition of induction chemotherapy prior to CT/XRT would result in improved survival. Methods: Between 10/1998 and 5/2002, 366 stage III patients (pts) were randomized to either immediate CT/XRT carboplatin AUC of 2 and paclitaxel 50 mg/m2 each given weekly during 66 Gy chest XRT to; arm 1 (182 pts) or two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m2 given q 21 days x 2 cycles followed by identical CT/XRT; arm 2 (184 pts). The accrual goal was 360 patients. 290 deaths were required to have 80% power to detect a 40% increase in median survival assuming a one-tailed log-rank test conducted at the 0.025 level of significance. Results: 34% of pts were female, 66% male and 63% were age 60 or older. Grade 3 or 4 toxicities during induction chemotherapy consisted mainly of neutropenia (17%/21%). During CT/XRT, grade 3/4 neutropenia was noted in 11%/4% (arm 1) versus 21%/6% (arm 2), grade 3 anemia was 5% vs 11%, grade 3/4 fatigue 16%/1% vs 16%/4%, esophagitis 30%/1% vs 28%/7%, and dyspnea 9%/3% vs 15%/4%. Overall, 4 toxicities were experienced by 24% of patients on arm 1 versus 41% on arm 2 (p=0.001). With 254 of 290 targeted deaths, median survival on arm 1 is 11.4 months versus 14 months on arm 2 (p=0.154). One year survival estimates are 48% (41%–57%) and 54% (47%–62%) respectively. Conclusion: The median survival achieved in each of the treatment groups is low compared to other recent experiences in the literature. The reason(s) for this are uncertain. The addition of induction chemotherapy to immediate concurrent CT/XRT is associated with a 2.6 month increase in median survival. However these findings are not sufficient to reject the null hypothesis of no treatment difference between the two study arms. Further follow up of this data set is required. Our results do not support the use of induction chemotherapy followed by CT/XRT as evidence based standard of care for patients with unresectable stage III NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Oncology Aventis Aventis