The appearance of a rash in cancer patients treated with erlotinib (Tarceva) is strongly associated with longer survival, according to researchers from the drug's developer, OSI Pharmaceuticals, Inc. This is not the first time that rash has been associated with a survival advantage with epidermal growth factor receptor (EGFR) inhibitors—a class of drugs that includes erlotinib, cetuximab(Drug information on cetuximab) (Erbitux), and panitumumab (Vectibix)—but it is the most detailed analysis to date.

The study, published in the July 1 issue of Clinical Cancer Research, reports that for patients taking erlotinib who developed a moderate to severe rash, survival without progression of disease was 245% longer than in patients who had a mild rash or none at all. In fact, in the majority of cases, the more severe the rash, the longer a patient's cancer was held in check, researchers found.

This rash, which often looks like acne, can be unpleasant enough for some people to consider discontinuing treatment, but "it is important for physicians and patients to understand that this a positive event because it means there is likely to be a better clinical outcome," said the lead author, Bret Wacker, director of biostatistics at OSI Pharmaceuticals, Inc. "Further studies are needed to both identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy."

Data From Two Large Studies

Although few patients dropped out of the large phase III clinical trials testing erlotinib in advanced non–small-cell lung cancer and pancreatic cancer due to the rash, Wacker said he fears those who are taking erlotinib outside of a clinical trial may be likely to stop treatment. According to the researchers, these rashes can be controlled with mild steroids or antibiotics, and in most cases, they will improve with treatment. They are believed to be due to an inflammatory response as a result of EGFR inhibition in skin tissue, Wacker said.

The analysis looked at two placebo-controlled, double-blind, randomized, phase III clinical trials testing erlotinib in advanced non–small-cell lung cancer and pancreatic cancer—studies that led to approval of the agent for treating both cancers. Wacker and his team excluded patients who died in the first month after starting the study because they may not have had time to develop the rash or the rash may have been underreported in these ill patients.

BR.21 Trial

Of the 673 patients in the lung cancer study, called BR.21, and in the erlotinib-treated group, 81% developed rashes, the majority of which were grade 2. The researchers found that the presence of any rash correlated with overall and progression-free survival and that these correlations increased with the grade of rash. Specifically, erlotinib-treated patients who did not develop a rash survived a median of 3.3 months, compared to 7.1 months for those with a grade 1 rash, and 11.1 months for patients with more severe, grade 2 rashes.

They also found, however, that 18% of patients treated with a placebo also developed a rash, and that overall survival in these patients was also significantly longer (a median of 8.2 months compared to 4.7 months), compared to placebo patients who didn't develop a rash. "We don't know why some patients treated with a placebo developed a rash, but it could be due to the strength of their immune system, and that is why they survived longer," Wacker said.

PA.3 Trial