Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301)
The Lancet Oncology, 05/24/2012
Atagi S et al. – For a select group of elderly patients with locally advanced NSCLC, combination chemoradiotherapy provides a clinically significant benefit over radiotherapy alone, and should be considered for this population.Methods
- This was a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301).
- Patients older than 70 years with unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy plus concurrent low-dose carboplatin [30 mg/m2 per day, 5 days a week for 20 days]) or radiotherapy alone, using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution.
- The primary endpoint was overall survival, which was analysed for the eligible population and stratified by ECOG performance status, stage, and institution.
- The trial was stopped early as a result of the second planned interim analysis.
- 200 patients were enrolled from Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the radiotherapy group.
- The second planned interim analysis was done 10 months after completion of patient accrual.
- At this time, median follow-up for censored cases was 19·4 months (IQR 10·3—33·5).
- In accordance with the prespecified stopping rule, the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group.
- Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22·4 months (95% CI 16·5—33·6) and 16·9 months (13·4—20·3), respectively (hazard ratio 0·68, 95·4% CI 0·47—0·98, stratified log-rank test one-sided p value=0·0179).
- More patients had grade 3—4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group, including leucopenia (61 [63·5%] vs none), neutropenia (55 [57·3%] vs none), and thrombocytopenia (28 [29·2%] vs two [2·0%]).
- Grade 3 infection was more common with chemoradiotherapy (12 patients [12·5%]) than with radiotherapy (four patients [4·1%]). Incidences of grade 3—4 pneumonitis and late lung toxicity were similar between groups.
- There were seven treatment-related deaths: three of 100 patients (3·0%) in the chemoradiotherapy group and four of 100 (4·0%) in the radiotherapy group.