Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: a phase II study based on surgical reassessment

Gynecol Oncol. 2010 Dec;119(3):451-6. doi: 10.1016/j.ygyno.2010.08.008. Epub 2010 Sep 15.

Abstract

Background: The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response (pCR) at reassessment surgery in epithelial ovarian, fallopian tube, or primary peritoneal cancers (OFPC).

Methods: Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or, after histologic confirmation of diagnosis, neoadjuvantly. Treatment included paclitaxel (175 mg/m²) and carboplatin (AUC 6) every 3 weeks for up to 6 cycles, plus oral erlotinib 150 mg daily. The primary objective was to determine whether the pCR rate at reassessment surgery was at least 60% after optimal cytoreduction at initial surgery (< 1cm residual disease), or at least 40% after suboptimal cytoreduction (at least 1cm residual disease) using a two-stage design (alpha=0.10, beta=0.10).

Results: The study population included 56 patients with stage III-IV OFPC. EGFR gene amplification was present in 15% of the 20 tumors evaluated. Twenty-eight patients had protocol therapy after optimal cytoreduction (stratum I), 23 had protocol therapy either after suboptimal cytoreduction (stratum II), and 5 received neoadjuvant therapy prior to cytoreduction (stratum III). Pathologic CR was confirmed in 8 patients (29%; 95% confidence intervals 13%, 49%) in stratum I and 3 patients (11%, 95% C.I. 2%, 28%) in stratum II, which did not meet the prespecified efficacy endpoint in either stratum.

Conclusions: Among unselected patients, erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride
  • Fallopian Tube Neoplasms / drug therapy
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / pathology
  • Fallopian Tube Neoplasms / surgery
  • Female
  • Gene Amplification / drug effects
  • Genes, erbB-1 / drug effects
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / surgery
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Young Adult

Substances

  • Quinazolines
  • Carboplatin
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Paclitaxel