A multicentre phase II trial of cabazitaxel in patients with advanced non-small-cell lung cancer progressing after docetaxel-based chemotherapy

Br J Cancer. 2016 Sep 27;115(7):784-8. doi: 10.1038/bjc.2016.281. Epub 2016 Sep 8.

Abstract

Background: Cabazitaxel, a semisynthetic microtubule inhibitor, has shown antitumour activity in models resistant to paclitaxel and docetaxel, and it has been approved for the treatment of docetaxel-resistant prostate cancer. We investigated its activity in patients with advanced non-small-cell lung cancer (NSCLC) progressing under or after docetaxel-based regimens.

Methods: Patients with locally advanced unresectable or metastatic NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled; patients had to have received up to two prior chemotherapy regimens for the treatment of advanced disease, including one docetaxel-containing regimen. Treatment consisted of cabazitaxel (25 mg m(-2) intravenously, every 21 days) until disease progression. The primary end point was the overall response rate.

Results: Among the 46 evaluable patients, 28.3% had squamous cell carcinoma and 54.3% had adenocarcinoma. Eight (17.4%) patients had received one and 38 (82.6%) two prior chemotherapy regimens. Treatment compliance was 95%; 26 (16%) cycles were delayed because of toxicity, (n=13) and dose reduction was required in 6 (13%) patients because of haematologic toxicity. Six (13%) patients achieved a partial response and 17 (37.0%) stable disease. The median progression-free survival and overall survival were 2.1 (95% confidence interval (CI): 1.0-3.2) and 7.4 (95% CI: 5.2-9.6) months, respectively. Grade 4 adverse events included neutropenia (n=8; 17%), febrile neutropenia (n=6; 13%) and thrombocytopenia (n=3; 6.5%). There was one treatment-related death.

Conclusions: Cabazitaxel exhibits activity in NSCLC patients pre-treated with docetaxel-based chemotherapy with a substantial but manageable toxicity profile. The drug merits further evaluation in this indication.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Squamous Cell / drug therapy
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Drug Substitution
  • Dyspnea / chemically induced
  • Fatigue / chemically induced
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Greece
  • Hematologic Diseases / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • Taxoids
  • Docetaxel
  • cabazitaxel