(CHICAGO, IL) – Afatinib significantly prolongs progression-free survival (PFS) among EGFR-mutation-positive lung cancer, compared to pemetrexed plus cisplatin, according to an analysis of the LUX-Lung3 study presented at the 2012 American Society of Clinical Oncology Annual Meeting.

Afatinib is a selective, irreversible ErbB blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4. Patients were tested for EGFR mutations and randomized 2:1 to receive afatinib (40mg daily; n=230) or intravenous pemetrexed (500mg/m2) plus cisplatin (75mg/m2) daily for up to six 21-day cycles (n=115). Baseline characteristics were well-balanced between the 2 study arms, reported lead author James Chih-Hsin Yang, MD, National Taiwan University Hospital, Taipei, Taiwan.

Afatinib was associated with a significantly longer median PFS than pemetrexed/cisplatin (11.1 vs. 6.9 months; HR=0.58; P=0.0004). Among 308 patients with common Dell9/L858R mutations, median PFS among afatinib patients was even longer (13.6 vs. 6.9 months for pemetrexed + cisplatin; HR=0.47; P<0.0001). Afatinib was also associated with a higher objective response rate (56% vs. 23%; P<0.0001) and longer delays in time to deterioration of cancer-related cough (HR=0.60; P=0.0072) and dyspnea (HR=0.688; P=0.0145).

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Afatinib-associated toxicities included diarrhea (95%), rash (62%), paronychia (57%), and dry skin (29.3%), Dr. Yang reported. Drug-related adverse event discontinuations occurred in 8% of afatinib-arm patients and 11.7% of pemetrexed/cisplatin-arm patients.  

“Almost 50% of afatinib patients had drug-related adverse events of grade 3 or higher, but we must note that the median follow-up was 16 cycles vs. only 6 cycles for chemotherapy, so there was a longer period to detect AEs,” Dr. Yang noted.

All health-related quality of life measures trended toward favoring afatinib. Overall survival rate analysis should be possible in 18 to 24 months, Dr. Yang said.  

LUX-Lung 3 is the largest prospective trial to date, of EGFR mutation-positive lung cancer, and is the first study using pemetrexed/cisplatin as a comparator.