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Afatinib improves PFS in patients with brain metastases

Patients with brain metastases receiving afatinib showed improved progression free survival in two phase 3 studies, compared with patients receiving chemotherapy, according to recent research.

Martin Schuler, MD, of the West German Cancer Center at the University Hospital Essen and University Duisburg-Essen in Essen, Germany, and colleagues compared the results of patients with brain metastases in two phase 3 studies. In LUX-Lung 3, researchers analyzed afatinib (Gilotrif, Boehringer Ingelheim) or cisplatin with pemetrexed in patients with metastatic lung adenocarcinoma with epidermal growth factor receptor (EGRF) mutations. In the randomized, open-label LUX-Lung 6, researchers compared the effects of BIBW 2992 or chemotherapy in patients with stage IIIB or stage IV lung adenocarcinoma with an EGRF-activating mutation. Schuler and colleagues analyzed objective response rate, progression free survival and overall survival in the brain metastases subgroups from both studies.

The PFS for patients taking afatinib in the LUX-Lung 3 study was 11.1 months vs. 5.4 months in patients receiving chemotherapy (HR = 0.54). Similarly, patients in LUX-Lung 6 taking afatinib had a PFS of 8.2 months vs. 4.7 months in the chemotherapy group (HR = 0.47). In a combined analysis of both studies, the researchers found afatinib showed a higher PFS for patients with brain metastases (8.2 months vs. 5.4 months in the chemotherapy group; HR = 0.50; P = 0.0297).

Schuler and colleagues noted that improvement in patients with brain metastases taking afatinib was at a comparable level to patients without brain metastases and that these patients also had an improved response rate compared to patients in the chemotherapy group.

“Given the apparent efficacy of afatinib, it is interesting to speculate how [tyrosine kinase inhibitors] could potentially become incorporated into current standard treatment regimens for patients with brain metastases,” Schuler and colleagues wrote in their study. “It is possible, for example, that treatment with a first-line TKI in patients with asymptomatic brain metastases could delay the requirement for whole brain radio therapy, thereby delaying or preventing exposure to the side effects of cranial irradiation.” – by Jeff Craven

Disclosure: Schuler reports personal fees from AstraZeneca, GlaxoSmithKline, Lilly, Novartis, and Pfizer, and grants from Boehringer Ingelheim and Novartis. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.