A randomized study of Erlotinib ( Tarceva ) plus Gemcitabine met its primary endpoint by demonstrating a statistically significant 23.5 percent improvement in overall survival ( or a hazard ratio of 0.81, which can also be referred to as a 19 percent reduction in the risk of death ) when compared to patients receiving Gemcitabine plus placebo.

The study was a multicenter, double-blind, placebo-controlled Phase III trial evaluating Erlotinib in patients with locally advanced or metastatic pancreatic cancer.

A total of 569 patients were randomized to receive either Gemcitabine plus concurrent Tarceva or Gemcitabine plus placebo.

In addition to the improvement in overall survival, 24 percent of patients receiving Tarceva plus Gemcitabine were alive after one year compared to 17 percent of patients receiving Gemcitabine plus placebo, a 41 percent increase in one-year survival.

Median survival in the Tarceva plus Gemcitabine arm was 6.4 months compared to 5.9 months in the Gemcitabine plus placebo arm.

Progression-free survival in the Tarceva plus Gemcitabine arm was also significantly improved by 32 percent ( or a hazard ratio of 0.76, which can also be referred to as a 24 percent reduction in the risk of progression ).

There was virtually no difference in tumor response: 9 percent in patients receiving Tarceva plus Gemcitabine versus 8 percent in the Gemcitabine plus placebo arm.

There were no significant differences in overall survival for patients whose tumors were shown to be EGFR-positive ( hazard ratio = 0.74, n = 86 ) versus those whose tumors were shown to be EGFR-negative ( hazard ratio = 0.82, n = 76 ).

The analysis of safety data did not reveal any unexpected safety signals beyond those seen in previous studies of Tarceva in both monotherapy and combination settings.

An increase in mild-to-moderate ( i.e. Grade 1 and 2 ) adverse events including rash, diarrhea and hematological toxicity were seen in the Tarceva plus Gemcitabine arm.
Rash was reported for 72 percent of patients who received Tarceva plus Gemcitabine and for 29 percent of patients who received Gemcitabine plus placebo.
Diarrhea was reported by 56 percent of patients who received Tarceva plus Gemcitabine and by 41 percent of patients who received Gemcitabine plus placebo.
Grade 3/4 rash in the Tarceva plus Gemcitabine arm was 6 percent compared to 1 percent in the Gemcitabine plus placebo arm.
Other grade 3/4 adverse events were similar in both arms, and rates for the events in the Tarceva plus Gemcitabine arm were infection ( 17 percent ), fatigue ( 15 percent ), diarrhea ( 6 percent ), dehydration ( 3 percent ) and pneumonitis ( 2 percent ).

Erlotinib is a small molecule designed to target the human epidermal growth factor receptor 1 ( HER1 ) pathway, which is one of the factors critical to cell growth in non-small cell lung cancer ( NSCLC ) and other solid tumors.
HER1, also known as EGFR, is a component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers.
Erlotinib inhibits the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth.
Tarceva is the only HER1/EGFR-targeted therapy proven to significantly prolong survival in second-line NSCLC as a single agent.

Tarceva was approved by the FDA in November 2004 and is an oral tablet indicated for daily administration for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.
Results from two earlier large, randomized, placebo-controlled clinical trials in first-line advanced NSCLC patients showed no clinical benefit with concurrent administration of Tarceva with doublet platinum-based chemotherapy ( Carboplatin and Paclitaxel or Gemcitabine and Cisplatin ) and its use is not recommended in that setting.

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005