Adjuvant therapy with gefitinib (Iressa), an epidermal growth factor receptor (EGFR)-targeted agent, was more successful at preventing recurrence than standard-of-care chemotherapy, in a phase III study of patients with EGFR-positive non–small cell lung cancer (NSCLC).¹ Gefitinib extended recurrence-free survival by about 10 months in patients with stage II–IIIA NSCLC. These findings were presented at the 2017 ASCO Annual Meeting.¹

“Adjuvant gefitinib may ultimately be considered an important option for stage II–IIIA lung cancer patients with activating EGFR mutations, and we may consider routine EGFR testing in this earlier stage of lung cancer [In the United States, EGFR testing is typically done later in the course of disease],” said lead author of the study, Yi-Long Wu, MD, Director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “We intend to follow these patients until we can fully measure overall survival, as opposed to disease-free survival, which just measures disease recurrence.”

The majority of patients with stage II–IIIA NSCLC treated with surgical resection and adjuvant chemotherapy have a recurrence, with a 5-year survival of about 40%. Approximately 25% of all NSCLC patients are candidates for potentially curative therapy. Of them, about 30% of patients in China have an EGFR-mutated tumor, which accounts for about 140,000 people worldwide whose tumors can be targeted with an oral inhibitor of EGFR. This group may have a prolonged recurrence-free interval with the use of adjuvant EGFR-targeted therapy compared to the administration of chemotherapy.

Yi-Long Wu, MD

Study Details

The study randomized 222 patients with completely resected, EGFR-positive, stage II–IIIA NSCLC to receive gefitinib at 250 mg daily for 24 months vs standard cisplatin-based adjuvant therapy every 3 weeks for 4 cycles (12 weeks total). All patients were followed for distant relapse for about 3 years. Chemotherapy was given for a shorter time than was gefitinib due to tolerance issues.

Previous studies of adjuvant therapy did not show any benefit for EGFR-targeted therapy, but these trials included unselected patients with NSCLC post surgery, Dr. Wu explained. The current study presented at the 2017 ASCO Annual Meeting is reportedly the first trial to compare gefitinib vs vinorelbine plus cisplatin in completely resected pathologic stage II–IIIA NSCLC patients with proven EGFR-activating mutations.

Key Findings

At the time of treatment cutoff, the median duration of treatment was 21.9 months for gefitinib and 4 cycles in the chemotherapy arm.

Median time to disease recurrence was 28.7 months for the gefitinib arm vs 18 months for the chemotherapy arm—representing a significant 40% reduction in recurrence risk favoring gefitinib (P = .005). Three-year disease-free survival was 34% with gefitinib vs 27% with chemotherapy (P = .013). In the overall study population, 76 deaths (34.2%) occurred during the trial; of them, 41 were in the gefitinib arm and 35 were in the chemotherapy arm (3 months).

Adjuvant gefitinib may ultimately be considered an important option for stage II–IIIA lung cancer patients with an active EGFR mutation.

— Yi-Long Wu, MD

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Patients treated with gefitinib had fewer serious adverse events (ie, grades 3 and 4) compared with those who received standard chemotherapy: 12% vs 48% (P < .001), respectively. In the gefitinib arm, the most common serious adverse events were elevated liver enzymes, whereas patients treated with chemotherapy had more vomiting, nausea, low blood cell counts, and anemia. No interstitial lung disease was reported in patients treated with gefitinib.

Tissue specimens were collected from these patients at surgery, and Dr. Wu and colleagues plan to analyze the specimens to identify potential biomarkers in addition to EGFR mutations for gefitinib response or resistance.

Awaiting Survival Data

At a press briefing before the 2017 ASCO Annual Meeting, ASCO President-Elect Bruce E. Johnson, MD, FASCO, said: “This study identifies a subset of patients who can potentially benefit from a targeted treatment that causes far fewer side effects than chemotherapy. It’s also clear evidence that we can use precision medicine not only in patients with advanced cancer, but also in those with earlier stage disease.”

Bruce E. Johnson, MD, FASCO

“In the adjuvant setting, it will take years of follow-up to show a survival benefit. The first positive finding is prolonged disease-free survival, with an encouraging hazard ratio. Ultimately, we are interested in whether adjuvant EGFR-targeted therapy improves survival. Dr. Wu is planning a survival analysis, and I will follow this closely,” Dr. Johnson continued.

Additional Considerations

Richard L. Schilsky, MD, FACP, FASCO, ASCO Chief Medical Officer, said that EGFR mutations are two to three times more frequent in lung cancer patients in Asia. “With this new information, many doctors may begin testing for EGFR mutations after surgery. If this treatment becomes an option, we will definitely test earlier.”

Dr. Schilsky noted that other factors will enter into the decision to use gefitinib or erlotinib (Tarceva) instead of standard chemotherapy. “In this trial, 12 weeks of chemotherapy were compared with 2 years of gefitinib. Two years is a big commitment for patients. The cost of gefitinib is also much higher than the cost of chemotherapy, so we have to consider the financial burden. There is a lot to discuss with patients, and whether this becomes a treatment option depends on demonstrating an overall survival advantage,” he commented. ■

DISCLOSURE: Drs. Wu, Johnson, and Schilsky reported no conflicts of interest.

REFERENCE

1. Wu Y-L, et al: Gefitinib versus vinorelbine + cisplatin as adjuvant treatment in stage II-IIIA (N1-N2) non-small-cell lung cancer with EGFR-activating mutation (ADJUVANT). 2017 ASCO Annual Meeting. Abstract 8500. Presented June 5, 2017.