Therapy-Induced Rash May Be a Sign of Longer Lung Cancer Survival

Key Point

Development of an erlotinib-associated rash may seem to be an inconvenience to lung cancer patients but may actually be predictive of improved survival.

The appearance of a rash in cancer patients treated with erlotinib is a common—but not undesirable—adverse effect, according to Bret Wacker, MS, and colleagues: In fact, the rash is associated with increased survival rates, as reported in the July 1 issue of Clinical Cancer Research. 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 which includes erlotinib, cetuximab, and panitumumab—but it is the most detailed analysis to date. The study was funded by OSI Pharmaceuticals, Inc.

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

Data for 673 patients in the lung cancer study were included in the analysis. Of the 444 patients in the erlotinib group, 81% developed a rash. On a scale of 1 (relatively mild) to 4 (severe), the majority of rashes were rated as grade 2. The presence of any rash correlated with overall and progression-free survival, and the strength of this correlation increased with the grade of rash. Specifically, erlotinib-treated patients who did not develop a rash survived a median of 3.3 months, compared with 7.1 months for those with grade 1 rashes and 11.1 months for patients with grade 2 rashes.

The researchers found that 18% of patients in the placebo group also developed a rash, and that overall survival in these patients was also significantly longer than for placebo patients who didn’t develop a rash (median, 8.2 vs 4.7 months, respectively). In the pancreatic cancer clinical trial that compared combination-therapy erlotinib plus gemcitabine with placebo plus gemcitabine in 521 patients, 71% of patients in the erlotinib/gemcitabine group developed a rash, compared with 30% of patients in the placebo/gemcitabine group.

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. Generally, the more severe the rash, the longer a patient’s cancer was held in check, the researchers found. “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,” said Mr. Wacker, lead author of the study and Director of Biostatistics at OSI Pharmaceuticals, Inc, in a released statement.

Although few patients dropped out of these trials due to the rash, Mr. Wacker said he has concerns about those who are taking erlotinib outside of a clinical trial.

Reference
Wacker B, Nagrani T, Weinberg J, et al. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res. 2007;13(13):3913-3921.

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