New data from the PA.3 randomised phase III trial of Erlotinib (Tarceva) + gemcitabine in locally advanced or metastatic pancreatic cancer was presented for the first time at ASCO GI on 27th January. The study was conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG).
Patients received either gemcitabine plus erlotinib, or gemcitabine plus placebo, for treatment of locally advanced or metastatic pancreatic cancer which had not previously been treated with chemotherapy. Prior radiotherapy for local disease was allowed. A total of 569 patients were randomised between November 2001 and January 2003. The two arms were well balanced at baseline. The primary endpoint of the study was overall survival, with a significant improvement in this endpoint seen in the gemcitabine plus erlotinib arm (p=0.025). The one year survival was 24 % in the gemcitabine plus erlotinib arm compared to only 17% in the gemcitabine plus placebo arm. Median survival was 6.4 months in the gemcitabine plus erlotinib arm, compared to 5.9 months in the gemcitabine plus placebo arm. In addition, progression free survival was significantly improved in the erlotinib arm with hazard ratio of 0.76, P=0.003. Response rate was similar in both arms (9% in erlotinib arm v. 8% in placebo arm). In terms of safety, as has been seen in other erlotinib trials, rash and diarrhoea were more common in the gemcitabine plus erlotinib arm. These were mostly mild to moderate in severity. Pulmonary toxicity occurred in only 5 patients (1.8%) in the gemcitabine plus erlotinib arm, compared to 1 patient (0.4%) in the gemcitabine plus placebo arm. The incidence of all other toxicities was similar in both arms.In conclusion, the study showed that the combination of gemcitabine and erlotinib is well tolerated, and significantly improves overall survival and progression free survival when compared to gemcitabine alone in advanced pancreatic cancer. This is the first placebo-controlled trial to demonstrate that any drug added to gemcitabine prolongs survival in patients with advanced/metastatic pancreatic cancer.