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25-07-2013 | Oncology | Article

Intercalated regimen demonstrates first-line efficacy for advanced NSCLC


Free abstract

medwireNews: Administration of erlotinib in combination with chemotherapy is a viable first-line treatment strategy in patients with advanced non-small-cell lung cancer (NSCLC), results from FASTACT-2 suggest.

In this phase 3 randomized controlled trial, intercalated therapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone, with the treatment benefit being restricted to patients with an activating epidermal growth factor receptor (EGFR) gene mutation.

Writing in TheLancet Oncology, the study authors note that while the treatment benefit was greater for patients with EGFR-activating mutations, there was no detrimental effect for those without mutations. Thus, while EGFR mutation testing should be implemented wherever possible, the authors “suggest that the regimen be considered for patients with an unknown mutation status in whom clinical parameters are suggestive of a high incidence of EGFR mutations.”

The FASTACT-2 (First-line Asian Sequential Tarceva And Chemotherapy) Trial included 451 patients with untreated stage IIIB/IV NSCLC who received six cycles of gemcitabine on days 1 and 8 plus platinum (carboplatin or cisplatin) on day 1. Additionally, patients were randomly assigned to receive intercalated erlotinib (n=226) or placebo (n=225) on days 15–28.

The study’s primary endpoint was median PFS. This was significantly longer with chemotherapy plus erlotinib than with chemotherapy plus placebo, at 7.6 versus 6.0 months, giving a hazard ratio (HR) of 0.57.

Intercalated therapy was also significantly associated with longer median overall survival (18.3 vs 15.2 months, HR=0.79). In all, 43% of patients on combination therapy had an objective response versus just 18% of those given chemotherapy plus placebo, a statistically significant difference.

EGFR mutation status was known for 241 patients (53% of the overall cohort). Of these individuals, 136 (56%) were wild-type for EGFR, eight (3%) had single resistance mutations, and 97 (40%) had EGFR-activating mutations. In the latter group, median PFS was 16.8 months with combination therapy versus 6.9 months with chemotherapy plus placebo, while median overall survival was 31.4 months versus 20.6 months, respectively.

In patients with wild-type EGFR, by contrast, neither of these endpoints differed significantly between the treatment groups. The most commonly reported adverse events were neutropenia, anemia, nausea, and rash, with skin toxicity being significantly more frequent with intercalated therapy than with chemotherapy alone.

“[T]his combination offers a new treatment option for patients with unknown EGFR status,” remark the researchers, who were led by Tony Mok (Chinese University of Hong Kong, Shatin). “Using this intercalated combination, treatment outcomes are potentially better than those with the standard chemotherapy regimen that patients with unknown EGFR status would otherwise receive.”

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Joanna Lyford, Senior medwireNews Reporter

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