1233PD - Efficacy and patient (pt)-reported outcomes (PROS) with selumetinib (AZD6244, ARRY-142866; SEL) + docetaxel (DOC) in KRAS-mutant advanced non-small...

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Pasi Janne
Authors P.A. Janne1, A. Shaw2, J. Rodrigues Pereira3, G. Jeannin4, J.F. Vansteenkiste5, C. Barrios6, F.A. Franke7, L. Grinsted8, I. Smith8, L. Crinò9
  • 1Lowe Center For Thoracic Oncology, Dana Farber Cancer Institute, Boston/US
  • 2Hematology/oncology, Massachusetts General Hospital, Boston/US
  • 3Depto De Pneumologia, Grupo de Assistencia Médica, 1224010 - Sao Paulo/BR
  • 4Service De Pneumologie, Hôpital Gabriel Montpied, Clermont- Ferrand/FR
  • 5Respiratory Oncology Unit (pulmonology), University Hospital Gasthuisberg, BE-3000 - Leuven/BE
  • 6Hospital Sao Lucas da PUC de Porto Alegre, Porto Alegre/BR
  • 7Cacon, Hospital de Caridade de ljui, Ljui/BR
  • 8Oncology, Astra Zeneca, Alderley Park/UK
  • 9Department Of Oncology, Hospital Santa Maria della Misericordia, 06100 - Perugia/IT

Abstract

Objectives

This randomized, double-blind, placebo (PBO)-controlled, phase II trial evaluated the efficacy and safety of SEL + DOC as second-line treatment for pts with KRAS-mutant advanced NSCLC. Assessment of the prevalence, severity, and change over time of lung cancer symptoms was an exploratory objective.

Methods

Pts with stage IIIB-IV, second-line KRAS-mutant advanced NSCLC, received iv DOC 75mg/m2, and po SEL 75mg or PBO BD. PROs were assessed using the Lung Cancer-Specific Symptom Questionnaire (LSSQ), which includes the Lung Cancer Subscale (LCS) plus items relating to symptoms and functional activities from the FACT-L. Pts completed the questionnaire on Day 1, and every 3 weeks until discontinuation from study treatment, and at discontinuation.

Results

422 pts were screened across 67 centers in 12 countries; 87 were randomized (SEL + DOC, 44; PBO + DOC, 43). Baseline characteristics were reasonably balanced. OS was longer for SEL + DOC vs PBO + DOC (9.4 vs 5.2 mo), but not statistically significant (HR 0.80; 80% CI 0.56–1.14) and hazards were non-proportional. All secondary endpoints, including response rate (37% vs 0%; p < 0.0001) and PFS (5.3 vs 2.1 mo; HR 0.58; 80% CI 0.42–0.79), were significantly improved for SEL + DOC vs PBO + DOC. Most frequent grade 3/4 AEs were neutropenia and febrile neutropenia. Compliance for completion of the LSSQ at baseline and at least 1 follow-up visit was 85.5%. There was a numerical improvement in the change from baseline in the LSSQ scores with SEL + DOC compared with PBO + DOC, throughout the assessment period. In a post-hoc analysis, the % pts with a clinically meaningful improvement in LCS score was greater for SEL + DOC (44%) than PBO + DOC (24%; OR 2.50; 80% CI 1.34–4.77; 1-sided p = 0.029). The time to deterioration of LCS score was also in favor of SEL + DOC (HR 0.33; 80% CI 0.22–0.49; 1-sided p = 0.0002).

Conclusions

This is the first prospective study to demonstrate a clinical benefit of targeted therapy (SEL + DOC) for pts with KRAS-mutant cancer of any type. In a post-hoc analysis, more pts experienced clinically meaningful improvements in lung cancer symptoms with SEL + DOC than PBO + DOC.

Disclosure

P.A. Janne: I have served as a consultant to Astra Zeneca and have been compensated.

A.T. Shaw: Research funding from Astra Zeneca and funding for costs of clinical trials.

J.F. Vansteenkiste: Dr. Vansteenkiste is the holder of the Astra Zeneca Chair in personalized lung cancer care which provides research funding.

L. Grinsted: Lynda Grinsted is an employee of Astra Zeneca and receives stock shares.

I. Smith: Ian Smith is an employee of Astra Zeneca and receives stock.

All other authors have declared no conflicts of interest.