Randomized Clinical Trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB Non-Small Cell Lung Cancer (NSCLC): Report of Cancer and Leukemia Group B (CALGB) Protocol 9633

Abstract

7019 Background: The value of adjuvant chemotherapy in resectable lung cancer remains controversial. The International Adjuvant Lung Trial (IALT) reported a modest but statistically significant survival advantage with cisplatin-based adjuvant chemotherapy in stages IA to III NSCLC. On the other hand, Adjuvant Lung Project Italy (ALPI) failed to demonstrate benefit for adjuvant chemotherapy in patients of similar stage. CALGB 9633 was designed to test the effectiveness of adjuvant chemotherapy in patients with T2N0M0, stage IB NSCLC. NCCTG and RTOG also participated. Methods: Within 4–8 weeks of resection, patients were randomized to adjuvant chemotherapy with paclitaxel 200 mg/m2 over 3 hours and carboplatin AUC 6, each administered on day one every three weeks for four cycles, or to observation. Eligibility: age >18 years, histologically documented NSCLC, T2 primary lesion, lobectomy or pneumonectomy, absence of tumor in N1 or N2 nodes sampled at surgery or mediastinoscopy. All p-values are two-sided. Results: Between 9/15/96 and 11/26/03, 344 patients were randomized. Median follow-up is currently 34 months. Median age was 61 years (range 34–81 years), and 64% were male. Groups were well balanced with regard to age, gender, race, ethnicity, histology, tumor differentiation, and resection type. 80% underwent mediastinoscopy prior to surgery. Lobectomy was performed in 89%. Adjuvant chemotherapy was well tolerated, and there were no chemotherapy-related toxic deaths. Grade III or IV neutropenia occurred in 36%. There have been 36 deaths from any cause among 173 patients in the chemotherapy group compared to 52 deaths among 171 patients in the observation group (HR=0.62; 95% CI: 0.41–0.95, p=0.028). Overall survival at 4 years is 71% (95% CI: 62%–81%) and 59% (95% CI: 50%–69%) in chemotherapy and observation groups, respectively. There was also a significant advantage in failure-free survival favoring the chemotherapy group (HR=0.69; 95% CI: 0.48–0.98; p=0.035). With regard to lung cancer mortality, there have been 19 lung cancer deaths in the chemotherapy group and 34 deaths in the control group (HR=0.51; 95% CI: 0.29–0.89; p=0.018). At 4 years, lung cancer mortality was 15% (95% CI: 8%–21%) and 26% (95% CI: 18%–34%) in chemotherapy and control groups, respectively. Conclusions: Adjuvant chemotherapy significantly reduces all-cause and lung cancer mortality in stage IB NSCLC. This is the first randomized trial to demonstrate significantly improved survival for a carboplatin-based adjuvant chemotherapy regimen in a uniform population with NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis