Prognostic factors in non-small cell lung cancer patients who are recommended to receive single-agent chemotherapy (docetaxel or pemetrexed) as a second- or third-line chemotherapy: in the era of oncogenic drivers and molecular-targeted agents

Cancer Chemother Pharmacol. 2015 Oct;76(4):771-6. doi: 10.1007/s00280-015-2843-3. Epub 2015 Aug 11.

Abstract

Purpose: Docetaxel or pemetrexed monotherapy is recommended either as a second-line treatment for non-small cell lung cancer (NSCLC) patients without EGFR mutation or ALK fusion genes or as a third-line treatment for patients with EGFR mutation or ALK fusion. However, efficacy and survival for these two settings have not been compared, leaving it unclear whether these two populations can be included in the same clinical trials. Moreover, prognostic factors for patients who are recommended to receive docetaxel/pemetrexed monotherapy are largely unknown.

Methods: Docetaxel or pemetrexed was administered to 67 EGFR wild-type patients as a second-line treatment following one platinum-based combination chemotherapy and to 17 EGFR mutant patients as a third-line treatment following EGFR tyrosine kinase inhibitors and one platinum-based combination chemotherapy. Docetaxel and pemetrexed were administered at 60 and 500 mg/m(2), respectively, every 3 weeks until disease progression, intolerable toxicity, or patient refusal. Overall survivals (OSs) between the two groups were compared using the log-rank test, and prognostic factors were evaluated via Cox's proportional hazards models.

Results: The median OS was 345.5 days in the EGFR wild-type second-line group and 616 days in the EGFR mutant third-line group. Multivariate analyses revealed that the stage before first-line treatment, performance status, and EGFR status were significant prognostic factors.

Conclusions: When planning clinical studies of NSCLC patients recommended to receive docetaxel or pemetrexed as single-agent chemotherapy, the EGFR status and stage before first-line treatment should be considered as stratification factors of randomized clinical studies.

Keywords: Chemotherapy; Molecular-targeted agents; Non-small cell lung cancer; Oncogenic driver; Prognostic factor.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Docetaxel
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / genetics
  • Female
  • Folic Acid Antagonists / adverse effects
  • Folic Acid Antagonists / therapeutic use
  • Humans
  • Japan
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Pemetrexed / adverse effects
  • Pemetrexed / therapeutic use*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Folic Acid Antagonists
  • Taxoids
  • Pemetrexed
  • Docetaxel
  • EGFR protein, human
  • ErbB Receptors