Adjuvant Treatment Yields Survival Benefit in Early-Stage NSCLC

NEW ORLEANS -Two phase III studies have shown that adjuvant chemotherapy after resection significantly improves survival for patients with early-stage non-small-cell lung cancer (NSCLC), compared with surgery alone. Previous randomized trials of cisplatin(Drug information on cisplatin) (Platinol)-based adjuvant chemotherapy in stages IA to III NSCLC have shown no survival benefit (Adjuvant Lung Project Italy, ALPI) or modest but significant benefit (International Adjuvant Lung Trial, IALT). The new results, from US and Canadian studies that enrolled only early-stage patients, were presented as late-breaking abstracts at the 40th Annual Meeting of the American Society of Clinical Oncology. CALGB 9633 Gary M. Strauss, MD, MPH, of Brown University and Rhode Island Hospital, reported that adjuvant carboplatin(Drug information on carboplatin) (Paraplatin) plus paclitaxel(Drug information on paclitaxel) provided a 4-year overall survival benefit of 12%, compared with observation (abstract 7019) in patients with stage IB NSCLC. This is the first randomized trial to evaluate this combination in the adjuvant setting in early-stage lung cancer. In this study, CALGB 9633, which was sponsored by CALGB, RTOG, and NCCTG, 344 patients with stage IB NSCLC (tumors at least 3 cm in diameter) who had undergone complete surgical resection of the tumor were randomized to receive paclitaxel 200 mg/m² over 3 hours and carboplatin AUC 6, each administered on day 1 every 3 weeks for four cycles, or to no further treatment. Median follow-up is 34 months. He noted that the mean tumor diameter was 4.6 cm. Overall survival at 4 years was 71% with chemotherapy vs 59% with observation. Death from any cause occurred in 38 treatment patients (21%) vs 52 controls (30%) (HR = 0.62, P = .028). This 38% proportional reduction in all-cause mortality with adjuvant chemotherapy translates into a 12% absolute improvement, Dr. Strauss said. Overall survival at 4 years was 71% with chemotherapy vs 59% with observation. Death from any cause occurred in 38 treatment patients (21%) vs 52 controls (30%) (HR = 0.62, P = .028). This 38% proportional reduction in all-cause mortality with adjuvant chemotherapy translates into a 12% absolute improvement, Dr. Strauss said. At 4 years, the risk of dying from lung cancer was 15% for patients who received chemotherapy vs 26% for controls. Overall, there have been 19 lung cancer deaths (11% mortality) with chemotherapy and 34 (20%) with observation (HR = 0.51, P =.018). This 49% proportional reduction in lung cancer mortality translates into an 11% absolute improvement with use of chemotherapy. Adjuvant chemotherapy was well tolerated, with no chemotherapy-related toxic deaths. Grade 3-4 neutropenia occurred in 36% of patients. "Our study demonstrates unequivocal efficacy for adjuvant chemotherapy in early lung cancer," Dr. Strauss concluded. JBR.10 In the Canadian study, 482 patients with completely resected stage I or II NSCLC were randomized to adjuvant vinorelbine (Navelbine)/cisplatin or observation. Five-year survival was 69% in the treated group vs 54% for observation (HR = 0.7, P = .012), for a 30% reduction in death and an absolute survival benefit of 15% (P = .0022), reported Timothy L. Winton, MD, on behalf of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) (abstract 7018). Dr. Winton is with the University of Alberta and the Capital Health-affiliated University of Alberta Hospital. In this study, JBR.10, patients received cisplatin 50 mg/m² on days 1 and 8 every 4 weeks for four cycles plus vinorelbine 25 mg/m² weekly for 16 weeks. The original protocol, which called for 30 mg/m²/wk of vinorelbine, was modified in August 1995 because of hematologic toxicity and patient compliance issues. Median survival in the adjuvant chemotherapy patients was 94 months vs 73 months for observation (HR = 0.69, P = .011). The average time to recurrence was 46.7 months for observation and has not been reached in the treatment arm. Dr. Winton reported that the combination was well tolerated. Impact on quality of life was limited, except for neurotoxicity. Discussant Katherine M.W. Pisters, MD, of M.D. Anderson, said that the two studies "confirm the positive IALT findings of a benefit for postoperative plantinum-based chemotherapy in completely resected NSCLC." She called adjuvant platinum- based chemotherapy in NSCLC a new standard of care that "should be recommended to completely resected NSCLC patients with good performance status."