Kate Johnson

May 18, 2017

New results could lead lung cancer experts to rethink adjuvant therapy for patients with resected stage II-IIIA non–small cell lung cancer (NSCLC).

The usual standard of care is cisplatin-based chemotherapy, but a new trial found that targeted therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib (Iressa, AstraZeneca) was better in patients with EGFR mutations.

The results come from the ADJUVANT (CTONG 1104) trial and were highlighted in a premeeting presscast for the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

"The authors reported a remarkable difference in disease-free survival," said Tony Mok, MD, from State Key Laboratory in Oncology in South China, Hong Kong, who was not involved in the study.

"The current standard is not to offer adjuvant EGFR TKI after resection of an early-stage EGFR-mutation-positive lung cancer, but the CTONG study helps us to rethink this paradigm. In other words, patients may be spared the toxicity of adjuvant chemotherapy and still attain a better disease-free survival," he told Medscape Medical News.

The study is "clear evidence that we can use precision medicine not only in patients with advanced cancer but also in those with earlier-stage disease," said ASCO President-elect Bruce E. Johnson, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts.

About 30% ― or 140,000 people worldwide ― have an EGFR mutation and may benefit from adjuvant treatment with EGFR-targeted therapy to reduce the chance of recurrence, according to ASCO.

"With this information now available, I suspect many doctors will begin testing these lung cancer tumors right after surgery to see if they actually have an EGFR mutation," said ASCO's chief medical officer, Richard Schilsky, MD, during the briefing.

"That is not currently standard of care in the US, where typically the testing doesn't take place until the cancer recurs or becomes metastatic," he added.

However, he suggested that even if other studies replicate these results, there are still issues such as cost and treatment duration to weigh in the balance.

Study Details

The phase 3 trial randomly allocated 222 patients with EGFR mutations to receive either gefitinib 250 mg daily for 2 years or the standard of care cisplatin/vinorelbine-based chemotherapy every 3 weeks for four cycles.

After a median follow-up of 36.5 months, there was a significant difference between the groups in recurrence-free survival: 28.7 months for patients who received gefinitib, and 18 months for those who received chemotherapy (hazard ratio [HR], 0.60; P = .005), reported lead study author Yi-Long Wu, MD, from the Guangdong Lung Cancer Institute, Guangdong General Hospital, in Guangzhou, China.

There was also a significant difference in the rate of serious adverse events (grade 3 or higher): 12.3% in the gefitinib group vs 48.3% with chemotherapy (P < .001).

Dr Wu noted that two recent trials of adjuvant targeted therapy did not show benefit in NSCLC and suggested that the negative results were due in part to the fact that they included disease of stages I, II, and III in their study. He also said that these "earlier trials only looked to see if patients showed overexpression or overactivity of EGFR, but not mutations in EGFR."

He noted that the current trial recruited patients "who had been confirmed to have activating EGFR mutations, so we believe these reasons account for why other trials showed no benefit of a targeted therapy while ours did."

Overall survival data in the current study is as yet immature, noted Dr Mok, and the results are limited because of the small sample size. But when considered along with the similar, ongoing Japanese IMPACT (WJOG6410L) study, "I trust we shall have a strong argument to offer adjuvant EGFR TKI instead of chemotherapy," he told Medscape Medscape News.

However, Dr Schilsky said that it is also important to bear in mind that in Dr Wu's trial, "we're talking about 12 weeks of chemotherapy vs 2 years of gefitinib. So it's a big commitment on the part of patients to adhere to 2 years of continuous treatment."

In addition, the cost of gefitinib is "far, far greater than the cost of 12 weeks of chemotherapy. And so I think at the end of the day, once the survival data are known, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit, what is the burden of the patients who take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment which, while it is less toxic, is not without toxicity, and what's the financial burden of that treatment choice going to be for the patient?"

This study received funding from the Chinese Thoracic Oncology Group (CTONG) and AstraZeneca China. Dr Wu has consulted for or served in an advisory role with AstraZeneca, Roche, Merck, Boehringer Ingelheim; has received honoraria from AstraZeneca, Lilly, Roche, Pierre Fabre, Pfizer, and Sanofi; and has received institutional research funding from Boehringer Ingelheim and Roche. Dr Mok has served as a speaker or as a consultant for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Vertex Pharmaceuticals, Bristol-Myers Squibb, geneDecode, OncoGenex, Celgene, Ignyta, Cirina, and Sanomic. Dr Johnson owns stock and has other ownership interests in the KEW Group; has received honoraria from Chugai Pharma and Merck; has consulted for or served in an advisory role with Amgen, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Clovis Oncology, Genentech, GlaxoSmithKline, the KEW Group, Lilly, Merck, Novartis, and Transgene; has received institutional research funding from Novartis; and has provided expert testimony for Genentech. Dr Schilsky has received institutional research funding from AstraZeneca, Bayer, BristolMyers Squibb, Genentech/Roche, Lilly, Merck, and Pfizer.

American Society of Clinical Oncology (ASCO) 2017 Annual Meeting. Abstract 8500, presented May 17, 2017.

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