Conferences > OncoLink Scientific Meetings Coverage > OncoLink at ASCO 2004 > Sunday, June 6, 2004

Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB non-small cell lung cancer: Report of Cancer and Leukemia Group B (CALGB) Protocol 9633

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Posting Date: June 6, 2004

Presenter: Gary M. Strauss
Presenter's Affiliation: Cancer and Leukemia Group B
Type of Session: Scientific

Background

• The role of adjuvant chemotherapy for early stage non-small cell lung cancer (NSCLC) has been controversial
• Recently reported studies regarding the role of adjuvant chemotherapy with completely resected NSCLC have been conflicting
• The International Adjuvant Lung Trial (IALT) showed a small, but significant overall survival benefit with adjuvant cisplatin-based chemotherapy for stage IA to III NSCLC
• The Adjuvant Lung Project Italy (ALPI) failed to demonstrate a benefit of cisplatin-based chemotherapy for similarly staged patients
• In particular, for stage I patients, there is no convincing randomized data regarding the benefit of adjuvant chemotherapy
• However, large numbers of stage I lung cancer patients continue to recur and die after complete resection
• This study was designed to examine the role of adjuvant chemotherapy for high-risk stage I NSCLC (defined as T2N0 (Stage IB))

Materials and Methods

• Patients with T2N0M0 stage IB NSCLC who underwent complete resection were randomized within 4-8 weeks of surgery between September 1996 and November 2003 to adjuvant chemotherapy (Arm 1) or observation (Arm 2)
• Patients were stratified by histology (squamous vs. other), grade (poorly differentiated vs. other), and mediastinoscopy (yes vs. no)
• All patients underwent lymph node sampling at the time of surgery and received either a lobectomy or pnemonectomy
• The overall accrual goal was 384 patients (previously revised downward from 700 patients due to poor accrual); however at a planned interim analysis, accrual was terminated after 344 patients due to a significant benefit seen for the adjuvant chemotherapy arm
• 344 patients were randomized with 14 patients found ineligible leaving 330 patients treated, though all 344 patients were included in the analysis
• Median follow-up was 34 months
• Chemotherapy consisted of carboplatin (AUC = 6) and paclitaxel (200 mg/m2) q3wks x 4 cycles
• Patient groups were well balanced with regards to age, gender, ethnicity, performance status, weight loss, histology, grade, presence of symptoms, tumor diameter, surgery extent, and mediastinoscopy

Results

• 4-year overall survival (OS): 71% (Arm 1) vs. 59% (Arm 2) (p=0.028)
• The hazard ratio (HR) for death was 0.62 (95% CI 0.41-0.95)
• 4-year failure free survival (FFS): 61% (Arm 1) vs. 50% (Arm 2) (p=0.035)
• HR for failure was 0.69 (95% CI 0.48-0.98)
• 24% of patients receiving chemotherapy experienced primary lung failures
• Adjuvant chemotherapy was well tolerated with no treatment-related toxic deaths
• Grade 3 or 4 neutropenia was seen in 36% of patients receiving chemotherapy
• 85% of patients received all four cycles of chemotherapy with 55% of patients receiving 4 cycles of full dose chemotherapy
• A competing risk analysis showed no difference between study arms with regards to death from other causes with 50% reduction in lung cancer mortality with the addition of adjuvant chemotherapy
• Multivariate analysis showed that only treatment with chemotherapy resulted in reduced mortality

Author's Conclusions

• Adjuvant chemotherapy reduces both lung cancer and all-cause mortality in patients with completely resected stage IB NSCLC
• The chemotherapy in this trial was very well tolerated
• This trial is the first randomized trial to show efficacy for carboplatin-based chemotherapy and the first to use a single TNM stage group of patients
• Carboplatin/paclitaxel x 4 is now an evidence-based option for adjuvant treatment of completely resected stage IB NSCLC

Clinical/Scientific Implications

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