There is ongoing debate about the efficacy of erlotinib (Tarceva) in patients with advanced non-small cell lung cancer (NSCLC) whose tumors have wild-type EGFR. In the TAILOR trial, reported in Lancet Oncology by Garassino and colleagues,1 erlotinib was compared with standard docetaxel as second-line treatment in patients with prior platinum-based therapy. The findings suggest that docetaxel is superior to erlotinib in this setting.
The TAILOR trial, conducted in 52 Italian hospitals, enrolled patients who had metastatic NSCLC, had received platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Of 702 patients screened, 540 were genotyped, and 222 were enrolled. These patients were randomized to receive erlotinib 150 mg/d (n = 112) or docetaxel 75 mg/m² every 21 days or 35 mg/m² on days 1, 8, and 15 every 28 days (n = 110). Randomization was stratified by center, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation. The primary end point was overall survival.
For the docetaxel vs erlotinib groups, median age was 67 vs 66 years, ECOG performance status was 0 or 1 in 93% vs 92%, histology was squamous in 21% vs 28% and adenocarcinoma in 75% vs 63%, 73% vs 83% were current or former smokers, 99% were white in both groups, 93% vs 92% had receive first-line chemotherapy and 6% vs 8% had received adjuvant chemotherapy, and best response to first-line chemotherapy was complete response in 0% vs 1% and partial response in 35% vs 44%.
After a median follow up of 33 months, docetaxel was associated with a borderline significant improvement in median overall survival (8.2 vs 5.4 months, adjusted hazard ratio [HR] 0.73, 95% confidence interval 0.53-1.00, P = .05). Median progression-free survival was significantly prolonged with docetaxel treatment (2.9 vs 2.4 months, adjusted HR 0.71, P = .02). Objective response occurred in 15.5% of the docetaxel group vs 3.0% of the erlotinib group (P = .003). Overall survival and progression-free survival outcomes across subgroups appeared to be better with docetaxel than with erlotinib, although many of the differences between groups were not significant. KRAS mutational status had no prognostic effect. In multivariable analysis, only treatment and performance status were associated with overall and progression-free survival.
Post-progression treatment in 51 patients in the docetaxel group consisted of pemetrexed in 18%, gemcitabine in 22%, vinorelbine in 35%, and, in violation of study protocol, erlotinib in 8%. Post-progression treatment in 53 patients in the erlotinib group consisted of pemetrexed in 42%, gemcitabine in 17%, vinorelbine in 26%, and in violation of study protocol, docetaxel in 15%.
Treatment-related adverse events led to dose modification in 22% of patients in the docetaxel group and 21% of erlotinib patients. Neutropenia, neurological toxic effects, alopecia, asthenia, and nausea were more common in the docetaxel group and most patients in the erlotinib group had skin toxic effects. The most common grade 3 or 4 toxic effects were low absolute neutrophil count (20% in the docetaxel group vs 0% in the erlotinib group), skin toxic effects (0% vs 14%), and asthenia (10% vs 6%). The authors noted that skin toxic effects were not a significant predictor of erlotinib response in the trial. One patient in each group died from treatment-related sequelae (grade 4 diarrhea in an erlotinib patient and febrile neutropenia in a docetaxel patient).
As stated by the investigators: “In conclusion, our results unequivocally show that—although neither docetaxel nor erlotinib are magic bullets for second-line treatment of NSCLC—a cytotoxic approach to treatment of patients with NSCLC is still the best option in the absence of a clear therapeutic target.” ■
1. Garassino MC, Martelli O, Broggini M, et al. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. July 22, 2013 (early release online).