Adjuvant Erlotinib Benefits Patients with EGFR-Mutated NSCLC

CHICAGO – For patients with resected non–small cell lung cancer bearing epidermal growth factor receptor mutations, daily maintenance with erlotinib was associated with good overall disease-free survival for at least 2 years, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Among 100 patients with NSCLC positive for mutations in the epidermal growth factor receptor (EGFR) who underwent surgery and routine adjuvant chemotherapy or chemoradiotherapy, maintenance with erlotinib (Tarceva) 150 mg daily was associated with a median 2-year disease-free survival of 94%, reported Dr. Joel W. Neal of the Stanford (Calif.) Cancer Institute.

Median overall survival has not been reached, the investigators noted in a poster session.

Only one patient had disease progression while on adjuvant erlotinib, and 10 experienced progression at least 6 months after stopping the drug, suggesting the presence of residual disease that may be sensitive to re-treatment with erlotinib, Dr. Neal said in an interview.

"We’ve encouraged repeat biopsies for patients who have progressed after treatment with adjuvant erlotinib, and of the patients who were biopsied, 6 of 8 had an identical mutation without a known mechanism of resistance," he said.

Five of these patients were evaluable for additional therapy, and all were found to be sensitive to further treatment with erlotinib, Dr. Neal reported.

However, toxicities with erlotinib required dose reductions in some patients, and 6 patients discontinued therapy before the end of the study due to adverse events that included rash, diarrhea, and fatigue.

An oncologist who was not involved in the study commented that he would need to see longer follow-up before he could be convinced of the benefits of adjuvant erlotinib in this population.

"I’m not sure about the toxicity of 2 years of therapy with a TKI [tyrosine kinase inhibitor] in a setting where you’re not quite sure whether you’re improving survival or just disease-free survival," said Dr. Michael J. Purtell, an assistant professor of oncology at Johns Hopkins University in Baltimore, said in an interview.

The investigators designed the study, dubbed SELECT (Surgically resected EGFR-mutant Lung cancer with adjuvant Erlotinib Cancer Treatment) to determine whether adjuvant erlotinib could provide a more robust survival benefit to patients than that afforded by conventional adjuvant chemotherapy – typically about 5-10%, they said.

Patients with EGFR mutation–positive, surgically resected stage IA-IIIA NSCLC received 6-9 months of routine adjuvant chemotherapy with or without radiation, and were then continued on oral erlotinib 150 mg daily for up to 2 years. The patients are followed with CT scans every 6 months for 3 years, then once a year for years 4 and 5.

A total of 36 patients were enrolled initially, but the study was later expanded to included 100 patients in all, after initial encouraging results.

The findings thus far suggest that "adjuvant erlotinib has, at least, a cytostatic effect on micrometastatic disease," the investigators wrote.

The study was supported by Genentech. Dr. Neal has received research funding from the company. Dr. Purtell had no relevant disclosures.

CHICAGO – For patients with resected non–small cell lung cancer bearing epidermal growth factor receptor mutations, daily maintenance with erlotinib was associated with good overall disease-free survival for at least 2 years, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Among 100 patients with NSCLC positive for mutations in the epidermal growth factor receptor (EGFR) who underwent surgery and routine adjuvant chemotherapy or chemoradiotherapy, maintenance with erlotinib (Tarceva) 150 mg daily was associated with a median 2-year disease-free survival of 94%, reported Dr. Joel W. Neal of the Stanford (Calif.) Cancer Institute.

Median overall survival has not been reached, the investigators noted in a poster session.

Only one patient had disease progression while on adjuvant erlotinib, and 10 experienced progression at least 6 months after stopping the drug, suggesting the presence of residual disease that may be sensitive to re-treatment with erlotinib, Dr. Neal said in an interview.

"We’ve encouraged repeat biopsies for patients who have progressed after treatment with adjuvant erlotinib, and of the patients who were biopsied, 6 of 8 had an identical mutation without a known mechanism of resistance," he said.

Five of these patients were evaluable for additional therapy, and all were found to be sensitive to further treatment with erlotinib, Dr. Neal reported.

However, toxicities with erlotinib required dose reductions in some patients, and 6 patients discontinued therapy before the end of the study due to adverse events that included rash, diarrhea, and fatigue.

An oncologist who was not involved in the study commented that he would need to see longer follow-up before he could be convinced of the benefits of adjuvant erlotinib in this population.

"I’m not sure about the toxicity of 2 years of therapy with a TKI [tyrosine kinase inhibitor] in a setting where you’re not quite sure whether you’re improving survival or just disease-free survival," said Dr. Michael J. Purtell, an assistant professor of oncology at Johns Hopkins University in Baltimore, said in an interview.

The investigators designed the study, dubbed SELECT (Surgically resected EGFR-mutant Lung cancer with adjuvant Erlotinib Cancer Treatment) to determine whether adjuvant erlotinib could provide a more robust survival benefit to patients than that afforded by conventional adjuvant chemotherapy – typically about 5-10%, they said.

Patients with EGFR mutation–positive, surgically resected stage IA-IIIA NSCLC received 6-9 months of routine adjuvant chemotherapy with or without radiation, and were then continued on oral erlotinib 150 mg daily for up to 2 years. The patients are followed with CT scans every 6 months for 3 years, then once a year for years 4 and 5.

A total of 36 patients were enrolled initially, but the study was later expanded to included 100 patients in all, after initial encouraging results.

The findings thus far suggest that "adjuvant erlotinib has, at least, a cytostatic effect on micrometastatic disease," the investigators wrote.

The study was supported by Genentech. Dr. Neal has received research funding from the company. Dr. Purtell had no relevant disclosures.

CHICAGO – For patients with resected non–small cell lung cancer bearing epidermal growth factor receptor mutations, daily maintenance with erlotinib was associated with good overall disease-free survival for at least 2 years, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Among 100 patients with NSCLC positive for mutations in the epidermal growth factor receptor (EGFR) who underwent surgery and routine adjuvant chemotherapy or chemoradiotherapy, maintenance with erlotinib (Tarceva) 150 mg daily was associated with a median 2-year disease-free survival of 94%, reported Dr. Joel W. Neal of the Stanford (Calif.) Cancer Institute.

Median overall survival has not been reached, the investigators noted in a poster session.

Only one patient had disease progression while on adjuvant erlotinib, and 10 experienced progression at least 6 months after stopping the drug, suggesting the presence of residual disease that may be sensitive to re-treatment with erlotinib, Dr. Neal said in an interview.

"We’ve encouraged repeat biopsies for patients who have progressed after treatment with adjuvant erlotinib, and of the patients who were biopsied, 6 of 8 had an identical mutation without a known mechanism of resistance," he said.

Five of these patients were evaluable for additional therapy, and all were found to be sensitive to further treatment with erlotinib, Dr. Neal reported.

However, toxicities with erlotinib required dose reductions in some patients, and 6 patients discontinued therapy before the end of the study due to adverse events that included rash, diarrhea, and fatigue.

An oncologist who was not involved in the study commented that he would need to see longer follow-up before he could be convinced of the benefits of adjuvant erlotinib in this population.

"I’m not sure about the toxicity of 2 years of therapy with a TKI [tyrosine kinase inhibitor] in a setting where you’re not quite sure whether you’re improving survival or just disease-free survival," said Dr. Michael J. Purtell, an assistant professor of oncology at Johns Hopkins University in Baltimore, said in an interview.

The investigators designed the study, dubbed SELECT (Surgically resected EGFR-mutant Lung cancer with adjuvant Erlotinib Cancer Treatment) to determine whether adjuvant erlotinib could provide a more robust survival benefit to patients than that afforded by conventional adjuvant chemotherapy – typically about 5-10%, they said.

Patients with EGFR mutation–positive, surgically resected stage IA-IIIA NSCLC received 6-9 months of routine adjuvant chemotherapy with or without radiation, and were then continued on oral erlotinib 150 mg daily for up to 2 years. The patients are followed with CT scans every 6 months for 3 years, then once a year for years 4 and 5.

A total of 36 patients were enrolled initially, but the study was later expanded to included 100 patients in all, after initial encouraging results.

The findings thus far suggest that "adjuvant erlotinib has, at least, a cytostatic effect on micrometastatic disease," the investigators wrote.

The study was supported by Genentech. Dr. Neal has received research funding from the company. Dr. Purtell had no relevant disclosures.