ONCOmmunity

First-Line Erlotinib Followed by Second-Line Cisplatin-Gemcitabine Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The TORCH Randomized Trial

By: Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F.

Cesare Gridelli, Paolo Maione, and Antonio Rossi, S.G. Moscati Hospital, Avellino; Fortunato Ciardiello, Ciro Gallo, Floriana Morgillo, and Flavia Cantile, Second University; Giampaolo Tortora, Federico II University; Ferdinando Riccardi, Cardarelli Hospital; Maria Carmela Piccirillo, Massimo Di Maio, Alessandro Morabito, and Francesco Perrone, National Cancer Institute, Napoli; Giampaolo Tortora, University of Verona, Verona; Vittorio Gebbia and Gianfranco Mancuso, Casa di Cura La Maddalena, Palermo; Giovenzio Genestreti, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola; Adolfo Favaretto, Istituto Oncologico Veneto, Padova; Saverio Cinieri, A. Perrino Hospital, Brindisi and European Institute of Oncology; Salvatore Siena, Niguarda Ca' Granda Hospital, Milano; Raffaella Felletti, San Martino Hospital, Genova, Italy; Ronald Feld, Natasha Leighl, Ming-Sound Tsao, Mauro Saieg, and Gilda da Cunha Santos, Princess Margaret Hospital/University Health Network, Toronto; Rafal Wierzbicki, Oncology Clinical Trials-Durham Regional Cancer Centre, Oshawa; and Yasmin Alam, Windsor Regional Cancer Centre, Windsor, Ontario; and Charles Butts, Cross Cancer Institute, Edmonton, Alberta, Canada.
J Clin Oncol. 2012 Jul 9.

Abstract

Purpose

Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence.

Patients and Methods

Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned.

Results

At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation.

Conclusion

In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.

PMID: 22778317 [PubMed - as supplied by publisher] Source: National Library of Medicine.