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Induction chemotherapy followed by concominant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell cancer: Initial analysis of a randomized phase III trial

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

Presenter: Everett V. Vokes
Presenter's Affiliation: Cancer and Leukemia Group B
Type of Session: Scientific

Background

• Induction chemotherapy has been shown to improve survival in patients with stage IIIB non-small cell lung cancer (NSCLC) compared to radiation (RT) alone
• Concurrent chemoradiotherapy (CT/XRT) has also been shown to be superior to sequential chemotherapy and RT
• Despite these findings, the majority of patients with stage III NSCLC recur with distant metastatic disease
• This trial was designed to examine effect of induction chemotherapy followed by concurrent CT/XRT compared to CT/XRT alone for unresectable NSCLC patients

Materials and Methods

• 366 patients with inoperable stage IIIA and selected stage IIIB NSCLC were randomized between October 1998 and May 2002 to either immediate CT/XRT (Arm A) or induction chemotherapy followed by CT/XRT (Arm B)
• Eligible patients had an ECOG performance status of 0-1; however, unlike other CALGB studies, inclusion criteria did not restrict patients with excessive weight loss
• CT/XRT consisted of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m2) given concurrently with radiotherapy (66 Gy to the chest)
• Induction chemotherapy consisted of 2 cycles of carboplatin (AUC = 6) and paclitaxel (200 mg/m2) given every 21 days followed by identical CT/XRT
• The study was designed to accrue 360 patients with an 290 expected deaths in order to detect a 40% difference in median survival with 80% power.
• Patients were stratified by measurable vs. evaluable disease

Results

• 331 patients were evaluated (Arm A, n=161. Arm B, n=170)
• Patient groups were well balanced with regards to gender, age, PS, measurable disease, and stage
• A higher percentage of patients in the Arm A had >5% weight loss (32% vs. 21%)
• Response rates were similar between the two groups (p=ns):
• Complete Response: Arm A = 7%, Arm B = 12%
• Partial Response: Arm A = 58%, Arm B = 48%
• Overall Response: Arm A = 66%, Arm B = 61%
• Median survival: 11.4 mo (Arm A) vs. 13.7 mo (Arm B) (p=0.154) with 254 of 290 expected deaths
• Three-year overall survival (OS): 18% (Arm A) vs. 24% (Arm B)
• Median failure-free survival: 7.0 mo (Arm A) vs. 7.8 mo (Arm B) (p=0.11)
• On multivariate analysis, only performance status and weight loss affected survival
• When patients with >5% weight loss were excluded from the study, there was still no difference in OS (15.9 mo (Arm A) vs. 14.3 mo (Arm B))
• The patterns of failure were similar between both arms with the majority of patients failing distantly
• Grade 3/4 toxicity was experienced by 61%/24% of patients in Arm A compared to 24%/41% in Arm B
• There was no difference between the two groups with regards to grade 4 neutropenia, grade 3/4 fatigue, grade 3 esophagitis, and grade 4 dyspnea

Author's Conclusions

• The median survival in both arms of this study is low compared to other published studies of concurrent CT/XRT for unresectable NSCLC.  The reason for this is unclear
• Although induction chemotherapy appeared to improved median survival somewhat, this did not reach statistical significance
• Increased toxicity was seen with the additional of induction chemotherapy
• It is possible that induction chemotherapy results in toxicity that interferes with the delivery of definitive CT/XRT
• CT/XRT without induction chemotherapy remains the standard treatment for unresectable NSCLC

Clinical/Scientific Implications

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