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In the continuation of a case-based discussion, moderator Corey J. Langer, MD, notes that a 46 year-old woman with ALK-positive NSCLC has progressed following 11 months on crizotinib. In general, the disease is stable with progression to only a single rib with increasing pain, Langer notes.
At this point, Karen L. Reckamp, MD, MS, recommends continuing treatment with crizotinib while treating the rib lesion with local therapy. This approach is effective for treating localized progression, including brain metastases. However, if a systemic progression became apparent, Reckamp would pursue a clinical trial investigating a second-generation ALK inhibitor.
The second-generation ALK inhibitors LDK378 and the AP26113 have both demonstrated activity in patients refractory to crizotinib, explains Roy S. Herbst, MD, PhD. Additionally, these agents seem to cross the blood-brain barrier and both are advancing rapidly through clinical trials. In the context of research, Herbst would rebiopsy patients following progression on targeted TKIs, to assess possible secondary mutations or marker changes.
If a clinical trial is not an option, cytotoxic chemotherapy remains an acceptable treatment options following progression on crizotinib. In many cases, Herbst believes, chemotherapy is underutilized in this setting causing these patients to be undertreated. In a patient with a good performance status and no access to a clinical trial, Herbst recommends single agent pemetrexed or carboplatin plus pemetrexed.