1282P - Topical: randomized phase III trial of erlotinib compared with placebo in patients with advanced non-small cell lung cancer (NSCLC) unsuitable for f...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Non-small-cell lung cancer
Biological therapy
Presenter Siow-Ming Lee
Authors S. Lee1, S. Upadhyay2, C. Lewanski3, S. Falk4, G. Skailes5, E. Marshall6, Y. Ngai7, R. Rudd7, A. Hackshaw7, C. Boshoff1
  • 1Oncology, University College London (UCL) Hospitals & UCL Cancer Institute, NW1 2PG - London/UK
  • 2Oncology, Scunthorpe General Hospital, Scunthorpe/UK
  • 3Oncology, Charing Cross Hospital, London/UK
  • 4Oncology, Yeovil District Hospital, Yeovil/UK
  • 5Oncology, Royal Lancaster Infirmary, Blackpool/UK
  • 6Oncology, Clatterbridge Centre for Oncology, Liverpool/UK
  • 7Cancer Research Uk & Ucl Cancer Trials Centre, UCL Cancer Institute, London/UK



Despite the recommendation to treat advanced NSCLC with platinum-based chemotherapy, the majority of these pts receive only active supportive care (ASC) because of poor performance or multiple co-morbidities. We previously showed that erlotinib significantly improved PFS in such patients, but with an enhanced OS and PFS effect in female pts. Here, we report mature OS data including the association of first-cycle rash (FCR).


670 pts with stage IIIB/IV NSCLC (ECOG PS 2/3 or PS 0/1 with multiple co-morbidities unsuitable for chemotherapy) were randomized to receive placebo (n = 320) or erlotinib 150 mg/day (n = 350) and ASC until disease progression/toxicity. OS, PFS, adverse events, and QoL were examined. Pre-specified subgroup analyses included erlotinib-rash ≤28 days of starting treatment (FCR), and EGFR where available.


Baseline characteristics were well balanced in these predominantly elderly NSCLC pts (median = 77 yrs, range 42-91). Among all pts, the hazard ratios (HRs) were 0.94 (95% CI 0.81-1.10, P = 0.46) for OS. Pts receiving erlotinib had a better PFS, HR = 0.83 (95% CI 0.71-0.97, P = 0.02). 59% of pts on erlotinib developed FCR. FCR was the only independent factor predictive of OS (HR = 0.17; P = 0.02) in a multivariate analysis containing rash, age, gender, histology, ECOG score and stage. There was a benefit for both OS (HR = 0.76, 95% CI 0.63-0.92, P = 0.01) and PFS (HR = 0.66, CI 0.54-0.80, P < 0.01), compared to placebo. The benefits were seen in all the subgps including those with the worst PS score (ECOG 3); OS HR = 0.58 and PFS HR = 0.41 & stage IV; OS HR = 0.66 and PFS = 0.56. The OS medians (months) were 6.2 (erlotinib-rash), 2.9 (no rash) and 4.1 (placebo). Continuous erlotinib, without rash, appeared to be associated with worse OS in some subgroups (e.g. males, ECOG 3). Results for EGFR and KRAS mutations are available on 390 pts. 7% (27/390) of pts had activating EGFR mutation; the benefits of erlotinib were seen regardless of EGFR status. KRAS mutations (19%, 73/390) were neither prognostic nor predictive of erlotinib benefit. Grade 3/4 diarrhea was more common with erlotinib (8.4% vs. 1.3%, p < 0.001); other adverse events were similar between groups.


Erlotinib prolongs PFS and OS in patients with advanced NSCLC considered unsuitable for chemotherapy, but only if they develop FCR.


All authors have declared no conflicts of interest.