Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC)

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 7, 2004

This presentation discusses the use of erlotinib for the treatment of NSCLC which has not been approved by the FDA.

Presenter: U. Gatzemeier
Presenter's Affiliation: TALENT study investigators
Type of Session: Scientific


There is a growing body of preclinical data demonstrating the anti-tumor efficacy of erlotinib (OSI-774), a potent oral inhibitor of HER1/EGFR tyrosine kinase phosphorylation. Studies have also established the use of erlotinib (OSI-774) in conjunction with various chemotherapy agents. In light of the non-overlapping toxicity profile of erlotinib and most chemotherapeutic drugs, its applicability in clinical practice seems particularly appealing. The TALENT study was designed as a placebo-controlled trial evaluating the use of cisplatin and gemcitabine chemotherapy with concurrent and continued erlotinib, as compared to placebo, in patients with advanced non-small cell lung cancer. 

Materials and Methods

  • Eligible patients had histologically-documented stage IIIB/IV NSCLC
  • No prior chemotherapy or other systemic therapy, including other targetted agents, was permitted
  • Patients had to have ECOG performance status of 0 or 1, and a life expectancy of at least 12 weeks
  • Patients were not tested for HER1/EGFR status, so both EGFR-positive and EGFR-negative tumors were enrolled
  • 1,172 patients were enrolled from 164 centers across the world
  • Patients were randomized to one of two arms:
  •     1) erlotinib 150 mg daily and 6 cycles of cisplatin-gemcitabine, followed by daily erlotinib alone until disease progression
  •     2) placebo daily and 6 cycles of cisplatin-gemcitabine, followed by daily placebo alone until disease progression
  • Both arms were well-balanced for age (median = 60 years), gender (25% female), stage (66% stage IV), and histology (38% adenocarcinoma)
  • Primary endpoint of the study was overall survival (OS), for which the study had 80% power to detect a 25% difference in OS
  • Secondary enpoints of the study were time to progressive disease (TTP), response rates (CR/PR = complete/partial remissions, SD = stable disease, PD = progressive disease), time to symptomatic progression, and safety


  • All results reported below are for arm 1 (erlotinib) vs. arm 2 (placebo).
  • Overall survival was not statistically significant between the two arms.
  •     Median survival = 9.9 months vs. 10.1 months
  •     1-year survival = 41% vs. 42%
  • There was no statistically significant difference in TTP between the two arms.
  •     Median TTP = 5.4 months vs. 5.6 months
  • The response rates (complete, partial, and stable disease) were comparable in the two arms.
  •     CR = 1.5% vs. 1.7%
  •     PR = 30% vs. 28.2%
  •     SD = 24.6% vs. 27.8%
  • None of these values were siginificant based on subgroup analysis by patients demographics, performance status, or histology.
  • Retrospective analysis of HER1/EGFR status did not clearly correlate with survival.
  • There was no quality of life improvement noted with use of erlotinib compared to placebo.
  • There was significantly more rash (70% vs. 20%) and diarrhea in the erlotinib arm compared to placebo.
  • There were similar rates of more serious adverse effects and fatal adverse effects in the two arms.
  • There were similar rates of withdrawal from therapy on both arms, most commonly for progressive disease.

Author's Conclusions

  • There is no survival benefit seen in this study with the use of concurrent erlotinib and chemotherapy compared to chemotherapy alone.
  • This finding differs from the survival benefit that has been seen with the use of erlotinib as second or third line therapy.
  • Retrospective analysis of EGFR status did not correlate with the survival results.
  • Other than rash and diarrhea, erlotinib was relatively well tolerated.

Clinical/Scientific Implications
The negative results presented here offer new clinical insight in the management of patients with advanced NSCLC. The lack of a survival benefit with erlotinib in conjunction with chemotherapy in patients with advanced NSCLC raises several questions for further research. Firstly, are these results likely to be reproduced by other similar studies? The results shown here have indeed been echoed in a second abstract presented at this year's ASCO, in the US-based TRIBUTE study. It should be recognized that while the two studies are very similar, the TRIBUTE trial naturally has patient and tumor demographics and a chemotherapy regimen more representative of US practice, compared to the European patients studied in the TALENT trial. Regardless, both trials sought to investigate the use of erlotinib together with NSCLC chemotherapy regimens, and both were negative for a survival benefit. A second issue is whether the concurrent and maintenance regimen of erlotinib might play a role in the underwhelming survival results seen here, rather than the drug itself. Finally, the lack of correlation between EGFR status and survival is a perplexing finding, given the mechanism of erlotinib and its previously documented anti-tumor efficacy as second and third-line therapy.  Future studies will likely incorporate some of these remaining questions, but for the present time it does not appear that there is a clear role for the addition of erlotinib to standard chemotherapy doublets in advanced NSCLC.     

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