CHICAGO, IL— Non-small cell lung cancer (NSCLC) tumors that progress on the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib/gefitinib and afatinib continue to depend on ErbB family receptor signaling, suggests data from the open-label phase 3 LUX-Lung 5 (LL5) clinical trial, presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
Patients in the study appeared to benefit from continuous ErbB family blockade with afatinib plus paclitaxel, which was associated with improved progression-free survival (PFS) but not overall survival (OS).
Continued ErbB family blockade with afatinib and paclitaxel “significantly improved” PFS and objective response rate (ORR) compared with chemotherapy alone among heavily pretreated patients with acquired resistance to reversible EGFR tyrosine kinase inhibition (erlotinib/gefitinib), and who had experienced disease progression on afatinib monotherapy, reported lead study author Martin H. Schuler, MD, of the West German Cancer Center, University Duisburg-Essen, in Essen, Germany, and coauthors.
“A statistically significant improvement in PFS was observed on A+P [afatinib plus paclitaxel] versus chemotherapy arm (median 5.6 vs. 2.8 months, hazard ratio [HR], 0.60; 95% CI: 0.43-0.85; P = 0.003),” Dr. Schuler reported. “ORR was also significantly higher in the A+P arm versus chemotherapy (32.1% vs. 13.2%; P = 0.0049).”
OS, however, was identical in both study arms: 12.2 months (P = 0.99, not significant).
A total of 202 patients with NSCLC who had experienced treatment failure with one line or more of chemotherapy and erlotinib/gefitinib (after ≥ 12 weeks of treatment), were administered afatinib (50 mg/day). After 12 weeks on afatinib, participants were eligible to be randomly assigned 2:1 to receive afatinib plus paclitaxel (40 mg/day + 80 mg/m2/week; n=134) or investigator’s choice single-agent chemotherapy (n=68).
The most common treatment-related adverse events with afatinib plus paclitaxel versus chemotherapy were diarrhea (53.8% vs. 6.7%), alopecia (32.6% vs. 15.0%), and asthenia (27.3% vs. 28.3%), Dr. Schuler reported.
Afatinib is an oral ErbB family blocker that irreversibly inhibits EGFR (ErbB1), HER2 (ErbB2), and ErbB4 receptor kinases. Previous retrospective, nonrandomized studies had also suggested that continued EGFR-inhibition therapy after disease progression might improve disease control.
- Schuler MH, Yang CH, Park K et al. Abstract 8019. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.