Adjuvant Paclitaxel Plus Carboplatin Compared With Observation in Stage IB Non–Small-Cell Lung Cancer: CALGB 9633 With the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups

Abstract

A B S T R A C T PurposeAdjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC. Patients and MethodsWithin 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m 2 intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival. ResultsThree hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P ϭ .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors Ն 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P ϭ .043). ConclusionBecause a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors Ն 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

Post-operative Treatment with Cisplatin and Vinorelbine in Chinese Patients with Non-small Cell Lung Cancer: A Clinical Prospective Analysis of 451 Patients

“…The IALT (International Adjuvant Lung Trial) shows that platinum-based chemotherapy for patients with NSCLC improves a 5-year survival rate by 4.1% (Arriagada et al, 2004), but there is no significant benefit after follow-up for 90 months (Arriagada et al, 2010). The CALGB 9633 trial results in a similar finding (Strauss et al, 2008). Furthermore, the ANITA (Adjuvant Navelbine International Trialist Association) and JBR-10 (National Cancer Institute of Canada Clinical Trial Group) trials also confirm the survival benefit of adjuvant cisplatinvinorelbine chemotherapy in patients with NSCLC at I-IIIA even after follow-up for 9.3 years (Winton et al, 2005;Douillard et al, 2006;Butts et al, 2010).…”

Adjuvant Treatment for Elderly Patients with Early-Stage Lung Cancer Treated with Limited Resection

“…Observational studies suggest these results may be extrapolated to elderly patients (32). The role of adjuvant chemotherapy in stage IB tumors remains controversial; the only RCT focused exclusively on these patients reported no significant survival advantage with the addition of chemotherapy (33). However, subgroup analyses suggested that adjuvant therapy may have a role in patients with tumors greater than or equal to 4 cm in size.…”

Effect of age on the efficacy of adjuvant chemotherapy for resected non–small cell lung cancer

“…[2][3][4][5][6][7][8][9] Studies conducted in the last decade have provided evidence that adjuvant chemotherapy after surgical resection improves outcomes for patients with resected stages II and IIIA disease and selected patients with stage I (large tumor size) NSCLC. [10][11][12][13][14] A recent meta-analysis of these newer trials, 15 which included 5 trials and 4584 patients, found a benefit for adjuvant chemotherapy. The magnitude of benefit was an 11% reduction in the risk of death and an absolute survival benefit of approximately 5% at 5 years.…”