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 Anticancer Agents
Non-Small Cell Lung Cancer
Therapy
Biological Therapy
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.