Platinum-Plus Regimens Equally Effective First Therapies for EGFR Wild-Type NSCLC

Summary

In a single-site, retrospective study comparing the efficacy of several platinum doublet regimens in patients with EGFR wild-type, nonsquamous non–small cell lung cancer, no differences were found in overall survival or response rate between platinum plus pemetrexed or nonpemetrexed therapies (eg, gemcitabine, taxanes).

  • retrospective study
  • EGFR wild-type
  • nonsquamous
  • non–small cell lung cancer
  • platinum
  • pemetrexed
  • gemcitabine
  • taxanes
  • targeted treatment
  • oncology clinical trials

This single-site, retrospective study compared the efficacy of platinum doublet regimens used as first-line chemotherapy for patients with EGFR wild-type, nonsquamous non–small cell lung cancer (NSCLC). Investigators found no difference in survival, response rate, and prognostic factors. Eun Joo Kang, MD, Korea University Guro Hospital, Seoul, Korea, reported study results in a poster presentation [Kang EJ et al. Ann Oncol. 2015].

Molecular research and targeted agents like gefitinib and erlotinib have improved outcomes for a subset of NSCLC patients with EGFR mutations. Yet, platinum doublet regimens remain first-line therapy for patients with EGFR wild-type NSCLC, which accounts for more than half of all NSCLC cases. In a randomized phase 3 study, overall survival (OS) was significantly better with pemetrexed + cisplatin than a nonpemetrexed therapy (gemcitabine + cisplatin) in a Western population composed of chemotherapy-naïve patients with adenocarcinoma (12.6 vs 10.9 months; P < .03) [Scagliotti GV et al. J Clin Oncol. 2008].

Dr Kang and colleagues conducted a retrospective analysis on 165 patients with EGFR wild-type nonsquamous NSCLC who had received first-line treatment with pemetrexed + platinum (PP) or nonpemetrexed + platinum (NPP) chemotherapy at Korea University Guro Hospital between 2007 and 2013, analyzing progression-free survival (PFS), OS, response rate, and prognostic factors.

Almost all patients (91.5%) had adenocarcinoma. Average age was 66 years and 71.5% were men. At diagnosis, 80.6% had stage IV disease. During treatment, 43% had received PP and 57% had received NPP. In the NPP group, patients had mainly received gemcitabine + carboplatin (37.2% of all NPP patients), paclitaxel + carboplatin (19.1%), gemcitabine + cisplatin (18.1%), docetaxel + cisplatin (11.8%), or paclitaxel + cisplatin (7.4%). Patient characteristics were similar in the PP and NPP groups.

No difference between the 2 groups was reported in median PFS (P = .12) or OS (P = .42), nor did OS differ depending on which specific regimen was used (P = .82). For patients who had received PP, median PFS and OS were 4.6 months (95% CI, 3.8 to 5.4) and 18.7 months (95% CI, 11.7 to 25.8), respectively. For patients who had received NPP, median PFS and OS were 6.2 months (95% CI, 3.4 to 5.0) and 12.2 months (95% CI, 10.3 to 14.1), respectively. There were no significant differences in response rate, which was 26.8% in the PP group and 28.7% in the NPP group (P = .78).

During multivariate analysis looking at prognostic factors, prolonged OS was associated with a few subgroups:

  • In PP patients:

    • Stages I–III at diagnosis

    • Metastasis restricted to lung, pleura, or both

    • Treatment > 2nd-line chemotherapy vs 1st-line only

  • In NPP patients:

    • Metastasis restricted to lung, pleura, or both

    • Treatment > 2nd-line chemotherapy vs 1st-line only

The data suggest no clear advantage in PFS, OS, or response rate for patients with wild-type EGFR, nonsquamous NSCLC given PP or NPP as first-line therapy. Although pemetrexed plus platinum has been regarded as superior in nonsquamous NSCLC, this study did not support that belief. Because the study was retrospective, relatively small-scale, and conducted only on patients from 1 hospital, further confirmation is needed.

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