AZD9291 and Rociletinib in T790M-Mutant NSCLC

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Presentations focused on the third-generation EGFR inhibitors AZD9291 and rociletinib (CO-1686) were some of the most exciting developments at the 2014 ASCO Annual Meeting, explains H. Jack West, MD. Over the past decade, great responses to gefitinib and erlotinib have been demonstrated for patients with EGFR-mutant non-small cell lung cancer (NSCLC); however, resistance inevitably occurs.

In approximately 60% of patients, resistance is the result of an acquired mutation in T790M, which is the targeted for the third-generation agents, notes West. In the studies presented at ASCO, these therapies demonstrated impressive responses. For patients with confirmed T790M mutations, the overall response rate was 64% with AZD9291 and 58% with CO-1686. As a result of these early findings, both therapies received the FDA's breakthrough therapy designation.

The efficacy of these agents provides a clear incentive to rebiopsy patients with acquired resistance to frontline EGFR inhibitors, notes West. Moreover, these exciting response rates warrant the travel and other logistical challenges involved in clinical trial participation.

In addition to the clear demonstrated of efficacy, the third-generation EGFR inhibitors are well-tolerated, West states. These highly selective agents target the T790M mutation, sparing wild-type EGFR and preventing many of the classical side effects seen with first-generation inhibitors. As a result, the rate of skin rash and diarrhea with each of these agents is low, West notes.