Study Finds No Predictive Value of ERCC1 Marker for Outcomes With Nonplatinum vs Platinum Therapies in NSCLC


Key Points

  • ERCC1-positive status was not predictive of better outcome with nonplatinum treatment in patients with NSCLC.
  • Platinum treatment was associated with better outcome in patients with squamous disease.

In the UK phase III ERCC1 trial reported in the Journal of Clinical Oncology, Lee et al found that presence of the excision repair cross complementing group 1 (ERCC1) biomarker did not predict better outcome with nonplatinum therapy in patients with non–small cell lung cancer (NSCLC).

Study Details

The study was conducted to assess the potential superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC and noninferiority for ERCC1-negative NSCLC. A marker-by-treatment interaction design was used with ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemotherapy-naive patients with stage IIIB or IV disease with squamous histology were randomized to receive cisplatin/gemcitabine or paclitaxel/gemcitabine, and those with nonsquamous histology were randomized to receive cisplatin/pemetrexed (Alimta) or paclitaxel/pemetrexed. The primary endpoint was overall survival. The effect of antibody status for XPF (clone 3F2) was also examined.

Outcomes in Squamous Disease

Of 648 patients, 177 had squamous histology and 471 had nonsquamous histology, with ERCC1-positive rates of 76.7% and 54.5%, respectively, and XPF-positive rates of 68.5% and 70.5%, respectively.

Study accrual for squamous patients was stopped early in 2012 due to the finding of inferior overall survival for nonplatinum vs platinum therapy (median overall survival = 7.6 months vs 10.7 months, hazard ratio [HR] = 1.46, P = .02). All hazard ratios exceeded 1.0, indicating better outcome with platinum therapy, regardless of ERCC1 status.

Outcomes in Nonsquamous Disease

Accrual for nonsquamous patients was stopped in 2013. No difference was observed in overall survival for nonplatinum vs platinum therapy among ERCC1-positive patients (median overall survival = 8.0 vs 9.6 months, HR = 1.11, 95% confidence interval [CI] = 0.85–1.44) or among ERCC1-negative patients (median overall survival = 10.3 vs 11.6 months, HR = 0.99, 95% CI = 0.73–1.33; P =.64 for interaction). Hazard ratios for overall survival were 1.09 (95% CI = 0.83–1.44) in XPF-positive patients and 1.39 (95% CI = 0.90–2.15) for XPF-negative patients (P = .35 for interaction). Hazard ratios for overall survival were 1.11 (P = .32) for ERCC1-positive vs ERCC1-negative and 1.08 (P = .55) for XPF-positive vs XPF-negative.

The investigators concluded: “Superior outcomes were observed for patients with squamous histology who received platinum therapy compared with non-platinum chemotherapy; however, selecting chemotherapy by using commercially available ERCC1 or XPF antibodies did not confer any extra survival benefit.”

The study was supported by Eli Lilly and University College London.

Siow Ming Lee, MD, PhD, of University College London Hospitals, is the corresponding author of the Journal of Clinical Oncology article.

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®.