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Boehringer Ingelheim to Present New Data on PGx NSCLC Drug Afatinib at ASCO Annual Meeting

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Originally published May 27.

Boehringer Ingelheim will present at an upcoming oncology conference new pharmacogenomic data on its investigational non-small cell lung cancer drug afatinib.

The company will present the data, gathered from an expanded patient cohort enrolled in a Phase Ib study, at the American Society of Clinical Oncology annual meeting in Chicago June 3-7.

Boehringer began developing the irreversible EGFR/HER2 inhibitor BIBW 2992, also called afatinib, in 2009. Qiagen subsidiary DxS is working with Boehringer to develop a genetic test for the investigational drug that will gauge which patients have certain EGFR mutations that make them unresponsive to it (PGx Reporter 06/24/2009).

According to a statement from Boehringer, the phase Ib study, called LUX-Lung 4, involved 26 NSCLC patients who acquired resistance to a reversible EGFR tyrosine kinase inhibitor, either erlotinib or gefitinib, because they harbored a mutation called T790M. This particular mutation occurs in approximately 50 percent of tumors from patients who develop resistance to reversible EGFR TKIs.

Patients in the study received BIBW 2992 and escalating doses of cetuximab. Researchers acquired tumor tissue from patients after they acquired resistance to erlotinib or gefitinib.

In preliminary studies, "researchers observed a tumor size reduction of up to 76 percent over a treatment period of up to five months," the company reported.

Analysis of the 26-patient cohort showed that 22 percent received the predefined maximum dose of afatinib, 40 mg daily, plus 500 mg/m2 of cetuximab. The most common adverse events were Grade 1/2 rash and Grade 1/2 diarrhea. Three patients had Grade 3 rash. Eight of 22 patients, or 36 percent, saw a confirmed partial response, which included 29 percent of patients in the study who had the T790M mutation.

At ASCO, Boehringer will report updated findings from this study, after having expanded the study cohort to 80 patients. The company is also studying BIBW 2992 for treatment of brain tumor metastases, glioblastoma, and other advanced solid tumors, and will present data in these areas at the upcoming meeting.

In addition to LUX-Lung 4, Boehringer has an extensive clinical development program for BIBW 2992. The company has finished enrolling patients in the Phase III LUX-Lung 3 trial, which will specifically investigate afatinib as a first-line treatment in patients with advanced NSCLC with EGFR mutations. Another ongoing phase III trial, LUX-Lung 6, is looking at the efficacy and safety of afatinib compared to standard chemotherapy for first-line treatment of NSCLC patients in different geographical regions with EGFR mutations.

At last year's ASCO meeting, researchers from National Taiwan University Hospital, Boehringer Ingelheim, Memorial Sloan-Kettering Cancer Center, and elsewhere presented data from a Phase II study of BIBW 2992 in 444 patients with stage IIIB/IV lung adenocarcinoma who had EGFR mutations in exons 18 through 21, identified by direct sequencing.

In that study, called LUX-Lung 2, the researchers noted tumor size reduction in 90 percent of patients. The objective response rate and the disease control rate were 62 percent and 94 percent, respectively, for del19; 52 percent and 85 percent for L858R; and 43 percent and 78 percent for other mutations based on investigator assessment.

Median PFS for the overall groups was estimated to be one year. Specifically, PFS was 12 months in del19; 16.3 months in L858R; and 15.6 months when combined. Drug-related adverse events seen in 95 percent of patients were diarrhea and rash/acne (PGx Reporter 06/16/2010).

In announcing its plans to present data at ASCO this year, Boehringer noted that ASCO and the National Comprehensive Cancer Network recently issued guidelines recommending EGFR mutation testing for patients with metastatic or recurrent NSCLC. Boehringer noted that its Rx/Dx partnership with Qiagen to develop a RT-PCR based companion tests to pick out best responders to BIBW 2992 is in line with the latest guidelines.

"The ASCO and NCCN EGFR mutation testing recommendations reinforce the importance of identifying the appropriate NSCLC patients for clinical trials," said Christopher Corsico, senior VP of Boehringer's medicine and regulatory group.

"Boehringer Ingelheim is committed to studying afatinib in patients with advanced NSCLC with EGFR mutations, in addition to other patient populations," Corsico added.

Experts estimate that between 5 percent and 20 percent of NSCLC patients have EGFR mutations. These kinds of mutations appear more readily in patients with adenocarcinoma, in Asians, or in former or non-smokers.

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