Watson, Dorothy

7007 Background: In 2004, preliminary results of CALGB 9633 demonstrated statistically significant evidence that adjuvant chemotherapy with paclitaxel and carboplatin (PC) improved disease-free (DFS) and overall survival (OS) in resected stage IB NSCLC. Indeed, the study was closed early by the DSMB after a planned interim analysis demonstrated a p value for OS less than a prespecified stopping boundary. However, two larger trials, NCIC-JBR10 and ANITA, have shown significant OS advantages with adjuvant chemo, but failed to demonstrate improved survival in the stage IB subset. This report provides more mature data from CALGB 9633. Methods: InCALGB 9633, stage IB patients (pts) were randomized following resection to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks ×4 cycles or to observation. While initially planned to accrue 500 pts, the accrual rate was <50% of expected. Because slow accrual allowed longer observation times for each pt, the accrual target was reduced to 384 pts. OS is the primary endpoint. The redesigned study had 80% power to detect a hazard ratio (HR) of 0.67 after 150 observed deaths using a 1-tailed logrank test conducted at the 0.05 level of significance. Results: Between 9/15/96 and 11/26/03, 344 pts were randomized. Median follow-up is 54 mo. Demographics and toxicity has been previously reported (JCO Sup, 22:621a, 2004). The current intent-to-treat analysis shows a significant improvement in DFS favoring adjuvant chemo (HR=0.74; 90% 2-sided CI: 0.57–0.96; p=0.027). There is a trend toward improvement in OS that is not significant (HR=0.80; 90% CI: 0.60–1.07; p=0.10). There is, however, a significant advantage in 3-yr survival (79% vs. 70%; p=0.045). Five-yr survival is not different (60% vs. 57%; p=0.32), although median follow-up is <5 yrs and CIs are wide. Continued follow-up is planned since only 131 of 150 deaths required for final analysis have been observed. Conclusions: This updated but “preliminary” analysis no longer shows a significant OS advantage for adjuvant chemotherapy in stage IB NSCLC. However, the re-designed study does not have adequate power to detect small differences in OS that may be clinically significant. Advantages in DFS and 3-yr survival support continued consideration of adjuvant PC in stage IB NSCLC. [Table: see text]

Purpose Adjuvant 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 Methods Within 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. Results Three 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 = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors ≥ 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043). Conclusion Because 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 ≥ 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.

Purpose To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. Patients and Methods Eligible patients (N = 587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). Results Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. Conclusion PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.