No Progression-Free or Overall Survival Benefit With Second- or Third-Line Erlotinib vs Docetaxel in EGFR-Unselected Japanese NSCLC Patients
In a Japanese phase III trial (DELTA) reported in the Journal of Clinical Oncology, Kawaguchi et al found that erlotinib (Tarceva) was associated with no progression-free survival or overall survival advantage as second- or third-line therapy in EGFR-unselected patients with non–small cell lung cancer.
Study Details
In this open-label trial, 301 patients with stage IIIB or IV NSCLC, previous treatment with one or two chemotherapy regimens, evaluable or measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were randomly assigned between August 2009 and July 2012 to erlotinib at 150 mg daily (n = 150) or docetaxel at 60 mg/m2 every 3 weeks (n = 151). The primary endpoint was progression-free survival. In total, 109 patients (73%) in the erlotinib group and 90 (60%) in the docetaxel group had EGFR wild-type disease. Study treatment was third line in 19% and 14%, respectively.
The erlotinib and docetaxel groups were genrally balanced for age (median, 68 and 67 years), sex (72% and 71% male), stage (IV in 80% and 81%), ECOG performance status (0 in 51% and 52%, 1 in 45% and 44%), smoking status (never for 26% and 25%), histology (adenocarcinoma in 69% and 68%), first-line treatment (platinum doublet in 94% and 93%), and second-line treatment (platinum doublet in 13% and 6%).
Outcomes in Unselected Population
Median progression-free survival time was 2.0 months in the erlotinib group and 3.2 months in the docetaxel group (hazard ratio [HR] = 1.22, P = .09). After median follow-up of 8.9 months, progression or death had occurred in 94.0% of the erlotinib group vs 91.4% of the docetaxel group. Median overall survival was 14.8 vs 12.2 months (HR = 0.91, P = .53). Response rates were 17.0% vs 17.9% (P = .88). Subgroup analyses for progression-free survival showed no significant differences between the two groups except for nonadenocarcinoma histology (HR = 1.60, P = .03), with all hazard ratios favoring docetaxel.
Outcomes by EGFR Status
There was a significant interaction between treatment and EGFR status for progression-free survival (P = .03) but not for overall survival (P = .20). In patients with EGFR wild-type tumors, progression-free survival was 1.3 months in the erlotinib group vs 2.9 months in the docetaxel group (adjusted HR = 1.57, P < .01). Median overall survival was 9.0 vs 10.1 months (P = .91). Response occurred in 5.6% vs 20.0% (P < .01).
In patients with EGFR mutations, median progression-free survival was 9.3 vs 7.0 months (adjusted HR = 0.82, 95% confidence interval [CI] = 0.43–1.53) and median overall survival was not reached vs 27.8 months (adjusted HR = 0.38, 95% CI = 0.10–1.10).
Subsequent treatment included docetaxel in 42% of the erlotinib group and EGFR tyrosine kinase inhibitors in 38% of the docetaxel group and other drugs in 31% and 28%, respectively. In the unselected population, there was no significant difference in overall survival between patients in the erlotinib vs docetaxel group who received subsequent therapy (HR = 0.96, P = .8).
The most common adverse events of any grade were rash with erlotinib (93%), and fatigue (71%), nausea (50%), and hematologic toxicities with docetaxel. Grade 3 or 4 leukopenia (64% vs 1%), neutropenia (80% vs 1%), and febrile neutropenia (15% vs 0%) were significantly more common (all P < .01) with docetaxel. Two erlotinib patients died from interstitial lung disease and one docetaxel patient died from infection.
The investigators concluded, “[T]he present study showed no significant difference in [progression-free survival] and [overall survival] when comparing docetaxel and erlotinib in EGFR-unselected patients with NSCLC. However, docetaxel was superior to erlotinib in terms of [progression-free survival] and response rate (but not [overall survival]) in patients with EGFR wild-type disease.”
Tomoya Kawaguchi, MD, of the National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by a grant from the Japanese National Hospital Organization Multi-Center Clinical Research for Evidence-Based Medicine. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
