EGFR Mutations Found in Half of Asian NSCLC Patients

Zosia Chustecka

February 20, 2014

While it is already known that Asian patients with non-small cell lung cancer (NSCLC) have a higher rate of EGFR mutations than that found among Western patients, the first prospective study puts the rate at much higher than was previously thought.

The PIONEER study, published in the February issue of the Journal of Thoracic Oncology, tested 1482 patients from 7 Asian regions, and found EGFR mutations at a rate of 51.4% overall. Previous estimates have put the rate at around 30% in Asian patients, and around 20% among white patients.

The finding suggests that about half of Asian patients with NSCLC have EGFR mutations, and so are candidates for EGFR-targeted therapies such as erlotinib (Tarceva) and gefitinib (Iressa) and similar agents.

The study was funded by AstraZeneca, the manufacturer of gefitinib.

Several clinical practice guidelines now recommend EGFR mutation testing before initiation of first-line therapy for advanced NSCLC, and several phase 3 trials have demonstrated the clinical efficacy of EGFR-targeted agents over chemotherapy when used as first-line therapy for patients whose tumors have these mutations, the authors comment.

First Epidemiologic Study

PIONEER is the first epidemiologic study of EGFR mutation frequency across Asian countries/regions, write Yuankai Shi, MD, from the Chinese Academy of Medical science in Beijing, and colleagues. The study was highlighted in a press release from the International Association for the Study of Lung Cancer.

Asked to comment, Tony Mok, MD, clinical professor at the Department of Clinical Pharmacology at the Chinese University of Hong Kong, said he was very familiar with the study, and told Medscape Medical News: "We must be careful with the number."

The newly reported high incidence "may or may not be the true population incidence," he said. Only patients with adequate tumor samples were tested, but many patients did not have a sample that was large enough and so were not tested, he said.

High Frequencies Found

The tumor samples came from previously untreated patients with histologically or cytologically confirmed advanced adenocarcinoma NSCLC (stage 3b or 4) at 51 investigational sites spread across mainland China, Hong Kong, India, the Philippines, Taiwan, Thailand, and Vietnam.

Ethnically, the majority of patients were Chinese (73.8%), and the remainder were Kinh (8.2%), Thai (8.0%), Indian (5.5%), Filipino (4.3%), Japanese (0.1%), and mixed or other (0.2%).

About half of the patients (52.6%) had never smoked, and 43.4% were female.

Dr. Shi and colleagues note that the frequency of EGFR mutations in Indian patients (rate of 22%) was significantly lower than in patients from other Asian countries, and was more comparable with that expected in a white population (approximately 20%). They also note that previous studies have reported EGFR mutation rates of 30% in Japanese and 36% in Korean patients.

The highest frequency of EGFR mutations was found in Asian females (mutation rate of 61.1%) and never-smokers (60.7%), the researchers note, adding that this is in agreement with several previous studies.

However, the frequency was also high in Asian males (44%) and in Asian heavy smokers (30%), which is much higher than rates that have been previously reported for European patients (8.2% in males and 5.8% in heavy smokers), they point out.

"Thus, physicians should not discount these other populations from EGFR mutation testing on the basis of clinical characteristics," they write.

The PIONEER study "has valuable clinical implications for the treatment of advanced NSCLC across Asia," the authors conclude. The study shows that large-scale testing is feasible, can be standardized, and can result in a high analysis success rate.

The observed frequency of EGFR mutations in Asian patients suggests that testing should be considered for all patients with stage 3 or 4 adenocarcinoma in an Asian population, they conclude.

The study was funded by AstraZeneca, manufacturer of gefitinib. Dr. Shi has disclosed no relevant financial relationships. Two coauthors report receiving speaker or consultancy fees from AstraZeneca, and 2 coauthors are company employees. Dr. Mok reports serving as an advisor/consultant for AstraZeneca Pharmaceuticals, AVEO Pharmaceuticals, BeiGene, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, GlaxoSmithKline, Merck Serono, Pfizer, Roche, and Taiho Pharmaceutical Co.

J Urol . 2014;9:154-162. Abstract


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