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Cancer Drug Information

  • Posted: 07/12/2013

FDA Approval for Afatinib Dimaleate

Brand name(s): Gilotrif

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

On July 12, 2013, the Food and Drug Administration (FDA) approved afatinib dimaleate (Gilotrif  tablets, made by Boehringer Ingelheim Pharmaceuticals, Inc.), for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. The safety and efficacy of afatinib have not been established in patients whose tumors have other EGFR mutations. Concurrent with this action, FDA approved the therascreen® EGFR RGQ PCR Kit (QIAGEN) for detection of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

The approval of afatinib dimaleate was based on the demonstration of improved progression-free survival (PFS) in a multi-center international open-label randomized (2:1) trial. This trial enrolled 345 patients with metastatic NSCLC whose tumors tested positive for EGFR mutations. Patients were  randomly assigned to receive afatinib dimaleate 40 mg orally once daily (n=230) or pemetrexed/cisplatin (n=115). Randomization was stratified according to EGFR mutation status (exon 19 deletion vs. exon 21 L858R vs. “other”) and race (Asian vs. non-Asian). The major efficacy outcome was progression-free survival (PFS) as assessed by an independent review committee (IRC).

Of the 345 patients enrolled, 65 percent were female, the median age was 61 years, 26 percent were Caucasian, and 72 percent were Asian. The majority of patients had a tumor sample with an EGFR mutation categorized as either exon 19 deletion (49 percent) or exon 21 (L858R) substitution (40 percent), and the remaining 11 percent had “other” mutations.

A statistically significant prolongation of PFS determined by the IRC was demonstrated for patients assigned to receive afatinib dimaleate treatment [HR 0.58 (95 percent CI: 0.43, 0.78); p < 0.001, stratified log-rank test].  Median PFS was 11.1 months in patients treated with afatinib dimaleate and 6.9 months in patients treated with chemotherapy. Objective response rates were 50.4 percent in patients treated with afatinib dimaleate and 19.1 percent in  patients treated with chemotherapy.  No statistically significant difference in overall survival between the two groups was demonstrated. In patients whose tumors had exon 19 deletions or exon 21 (L858R) substitution mutations, median PFS was 13.6 months in those treated with afatinib dimaleate and 6.9 months in those treated with chemotherapy.

The most frequent ( at least 20 percent incidence) adverse reactions from afatinib dimaleate were diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite and pruritus.

Serious adverse reactions were reported in 29 percent of patients treated with afatinib dimaleate. The most frequent serious adverse reactions were diarrhea (6.6 percent), vomiting (4.8 percent), and dyspnea, fatigue, and hypokalemia (1.7 percent each). Fatal adverse reactions in patients treated with afatinib dimaleate  patients included pulmonary toxicity/ interstitial lung disease (ILD)-like adverse reactions (1.3 percent), sepsis (0.43 percent), and pneumonia (0.43 percent).

The recommended dose and schedule for afatinib dimaleate is 40 mg orally once daily until disease progression or until it is no longer tolerated by the patient. Afatinib dimaleate should be taken at least one hour before or two hours after a meal.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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