Afatinib Effective in Treating Late-Stage NSCLC

Chicago—Patients with advanced stage non–small cell lung cancer (NSCLC) who took the investigational oral agent afatinib had a significantly longer progression-free survival compared with those who received a standard combination chemotherapy regimen of cisplatin plus pemetrexed, according to a randomized, open-label, phase 3 study. Afatinib is a once-daily irreversible ErbB family blocker developed by Boehringer Ingelheim.

James Chih-Hsin Yang, MD, PhD, the study’s lead author and a professor at National Taiwan University, presented the results in a late-breaking oral abstract session at the ASCO meeting.

“Afatinib significantly improved rates of response and disease control versus chemotherapy, and the safety profile of afatinib was consistent with previous afatinib phase 2 studies,” Dr. Yang said.

Previous trials found cisplatin and pemetrexed were effective and well tolerated in this patient population, but this was the first study to compare the therapy with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor such as afatinib.

Testing the drug as a first-line treatment, this study (LUX-Lung 3) included 345 patients with stage IIIb or IV NSCLC harboring EGFR mutations. Patients were randomized in a 2:1 ratio to receive 40 mg per day of afatinib (n=230) until their disease progressed or tumor grew, or up to 6 cycles of 75 mg/m² of cisplatin plus 500 mg/m² of pemetrexed administered intravenously (n=115).

Patients enrolled between August 2009 and February 2011 at 133 sites in 25 countries were followed for a median of 16.4 months. The groups were well balanced, with an average age of 61 years; 65% of patients were female and 72% were of Eastern Asian ethnicity.

Median progression-free survival was 11.1 months in the afatinib group compared with 6.9 months in the chemotherapy group (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.43-0.78; P=.0004). At 12 months, 47% of patients in the afatinib group and 22% of patients in the chemotherapy group had not progressed.

A preplanned analysis of patients with 2 common EGFR mutations also favored the afatinib group, with median progression-free survival of 13.6 months compared with 6.9 months in the placebo group (HR, 0.47; 95% CI, 0.34-0.65; P<.0001). The analysis included 308 of the 345 patients in the study. After 12 months, 51% of patients who received afatinib and 21% of patients who received cisplatin plus pemetrexed had no disease progression.

As of February 2012, when the analysis occurred, 64% of patients had disease progression; 65 patients in the afatinib group and none in the chemotherapy group remained on treatment.

The objective response rate in the afatinib group was 56.1% compared with 22.6% in the chemotherapy group (P<.001). The median duration of response was 11.1 months in the afatinib group and 5.5 months in the chemotherapy group.

Only 2 patients did not experience an adverse event (AE), and nearly 50% had a grade ≥3 drug-related AE. However, Dr. Yang noted that patients in the afatinib group had a median of 16 cycles of treatment, while patients in the chemotherapy group had a median of 6 cycles. In addition, 7.9% of patients in the afatinib group and 11.7% of patients in the chemotherapy group had an AE that led to study discontinuation.

The most common AEs in the afatinib group were diarrhea (95.2% of patients), rash/acne (89.2%), stomatitis/mucositis (72.1%), paronychia (56.8%), and dry skin (29.3%). In the chemotherapy group, 65.8% of patients had nausea, 53.2% had decreased appetite, 46.8% had fatigue, and 42.3% had vomiting.

The time to deterioration in cough, dyspnea, and pain was longer in the afatinib group compared with the chemotherapy group. Further, patients who received afatinib had better overall health and quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30.