More people in the United States die from lung cancer than any other type of cancer. This is true for both men and women. According to the most currently available epidemiologic data from the US Centers for Disease Control and Prevention, 208,493 people were diagnosed with lung cancer in 2008, including 111,886 men and 96,607 women; among those, there were a total of 158,592 deaths from lung cancer.1 A recent report from the American Cancer Society estimates that there will be a total of 226,160 newly diagnosed cases of lung cancer in the US in 2012; of these, 160,340 will die of the disease.2 In accordance with this high prevalence, there were more abstracts presented for lung cancer than any other cancer type at the 2012 American Society of Clinical Oncology Annual Meeting.
In one abstract entitled “SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy,” Dr Edward S. Kim and his colleagues from the University of Texas MD Anderson Cancer Center, Houston, TX, investigated whether the addition of cetuximab to standard chemotherapy improved progression-free survival (PFS) in patients with recurrent or progressive NSCLC after failure of platinum-based therapy.3
In this multicenter, open-label, randomized Phase 3 trial, patients received either pemetrexed (500mg/m2; n=605) or docetaxel (75mg/m2; n=333) on Day 1 and were then randomized within each group to receive chemotherapy plus cetuximab (400/250mg/m2) or chemotherapy alone. Therapy was administered in six 3-week cycles. Patients were followed until the primary end point of PFS for pemetrexed plus cetuximab (PC) vs pemetrexed was reached; secondary end points were overall survival (OS), objective response rate (ORR), and duration of response (DOR).
Unfortunately, no significant difference was determined for median PFS (2.89 months, PC-arm vs 2.76 months, pemetrexed arm; HR=1.03 [95% CI=0.87–1.21]; P=0.76) as well as for median OS 6.93 months, PC vs 7.79 months, pemetrexed; HR=1.01 [95% CI=0.86–1.20]; P=0.86). Differences in ORR and in median DOR were also found to be nonsignificant. The results were disappointing but not surprising, however, as investigators reported that no patient in either treatment arm achieved a complete response.
Drug toxicity was not terribly different between arms. However, more drug-related adverse events and serious adverse events were observed in the PC arm, with actual differences in skin toxicities, gastrointestinal events (eg, diarrhea, stomatitis), and hypomagnesemia. Although it is likely that cetuximab will not be added to regimens containing pemetrexed based on the lack of efficacy observed in this patient population, other combinations with cetuximab are worth investigating.
In another abstract entitled “LUX-lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations,” lead author James Chih-Hsin Yang, MD, of National Taiwan University Hospital, Taipei, Taiwan, and colleagues investigated the effectiveness of afatinib, a member of the ErbB blocker family, and a selective, irreversible blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4.4 In this study, the investigators were targeting the EGFR mutation-positive NSCLC population. Accordingly, patients were tested for EGFR-activating mutations at the time of enrollment in this study. Randomized patients received afatinib (40mg daily; n=230) or intravenous pemetrexed (500mg/m2) plus cisplatin (75mg/m2) daily for up to six 21-day cycles (n=115); patients were followed to a primary end point of progression-free survival (PFS).