Rash Signals Better Outcome for Erlotinib Therapy in NSCLC

OncologyLive, August 2012, Volume 13, Issue 8

Cutaneous rash is a common adverse event among patients with non-small cell lung cancer who receive erlotinib and may indicate that the patient will experience a significantly greater survival benefit.

Román Pérez-Soler, MD

Professor of Medicine, Chief, Division of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY

Cutaneous rash is a common adverse event among patients with non-small cell lung cancer (NSCLC) who receive erlotinib, but if it develops early on in the treatment course, it could be an indication that the patient will experience a significantly greater survival benefit.

That correlation emerged from a retrospective analysis of patients who took erlotinib in a study launched more than a decade ago.

Erlotinib inhibits the tyrosine kinase associated with epidermal growth factor receptor (EGFR), and the new data build upon the knowledge of how agents in this class of inhibitors affect patients, said Román Pérez-Soler, MD, lead author of the study, which was presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago in June.1

“We know that all the EGFR inhibitors produce this side effect, and now we have more and more of these agents being developed for a wide variety of diseases,” said Pérez-Soler. “It was very intriguing to observe that individuals that presented with severe rash tended to live longer. This triggered a lot of discussion whether there was a real correlation between the two.”

The study presented at ASCO was a subanalysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) BR.21, the pivotal phase III trial that began in 2001 and led to the FDA approval three years later of erlotinib for the treatment of locally advanced or metastatic NSCLC under the brand name Tarceva (Genentech/Astellas).

The BR.21 study enrolled 731 patients with stage IIIB or stage IV NSCLC who had failed first- or second-line chemotherapy. Those patients were randomized in a 2:1 ratio to treatment with either erlotinib (n = 488) or a placebo (n = 243). However, three patients in the erlotinib arm and one patient in the placebo arm did not receive any study drug.

In the subanalysis, Pérez-Soler and colleagues found that 366 of the patients who received erlotinib (75%) developed a rash at any point in time during treatment, while 40 patients in the placebo group developed a rash (17%).

Among patients treated with erlotinib, 75% of rash episodes occurred within the first two weeks of treatment, and 95% were reported within 10 weeks. The incidence of rashes varied depending on the grade, with grade 1 and 2 rashes peaking by the third week of treatment and grade 3 rashes peaking at the fifth week.

Table. Median OS by Rash Status

in Patients on Erlotinib1

Rash Grade

Rash Group


No Rash Group


Any grade

37.4 wks (311)

11.1 wks (65)

Grade ≥2

40.4 wks (193)

Grade 1

30.2 wks (118)

OS indicates overall survival.

Rash Group was defined as patients presenting with cutaneous rash by week 10 of erlotinib therapy. No Rash Group consists of 55 patients who did not present with any rash and 10 patients who presented with skin toxicity after week 10.

The researchers used the 10- week mark to analyze the impact of skin toxicity; patients who developed a rash by week 10 were placed in the “rash group,” while those who either did not experience any rash or presented with a rash after week 10 were placed in the “no rash” group (Table).

In all, 311 patients developed a rash by week 10 of erlotinib therapy. The median overall survival (OS) of patients in the “rash” group was 37.4 weeks. For the 65 patients in the “no rash” group, median OS was 11.1 weeks (HR = 0.51; 95% CI, 0.38-0.68; P < .0001).

For most patients, the rash was not a barrier to treatment, the researchers found. The rash most frequently presented within the first two weeks, peaked during weeks 3-5, and decreased thereafter, according to the abstract. The erlotinib dose was reduced for 48 patients (10%), and seven patients discontinued erlotinib because of skin toxicity.

While the study suggests an association between rash and outcome, Pérez-Soler said that the reasons this happens are still unclear.

“We don’t know the mechanism behind this,” he said. “It could be rather complex.”

Erlotinib is depicted in a ball-and-stick figure amid the gray surface of the epidermal growth factor tyrosine kinase domain.

Pérez-Soler said the development of the rash could be associated with more of the drug entering the bloodstream, which results in a greater antitumor effect. However, Pérez-Soler said that this is a hypothesis because some patients who receive enough of a dose of the drug do not develop a rash.

Regardless of the mechanism, Pérez-Soler said that oncologists prescribing erlotinib would be able to use this evidence to reassure patients who develop a rash that it might be a sign of efficacy.

“I think it makes sense to at least tell the patients that if they have rash and they are uncomfortable, at least we know that we have observed a positive correlation between the ability to present this rash and the final outcome,” Pérez-Soler said.


Román Pérez-Soler, MD, is a program director of the 7th New York Lung Cancer Symposium scheduled for November 10, 2012, in New York City. For more information, visit www.gotoper.com. 1. Pérez-Soler R, Leon L, Wojtowicz-Praga S, et al. Cutaneous toxicity secondary to erlotinib therapy in patients with non-small cell lung cancer in the NCIC CTG BR.21 study: time course and correlation with survival. J Clin Oncol. 2012;30(suppl; abstr 7573).