These are three new drugs that are each approved for a different disease. ADCETRIS (brentuximab vedotin) is and conjugate of an anti-CD30 antibody and the microtubule disrupting agent MMAE. It is indicated for treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for Systemic Anaplastic Large Cell Lymphoma after failure of at least one prior multi-agent chemotherapy regimen. Zelboraf is anti BRAF kinase inhibitor. ZELBORAF™ is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test. XALKORI is a tyrosine kinase inhibitor indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. It is similar to Zelboraf in that it is only effective in canners with specific mutations and it is similar to Adcetris in that it has an indication for Anaplastic Large Cell lymphoma, but unlike Zelboraf, it will only work for the ALK-positive mutation. Both Zelboraf and Xalkori can only be used after a test identifies an BRAF or ALK mutation respectively.
None of these drugs have been tested in combinations with one another.
As FDA indicated agents, each will find a place. Because therapies that depend on specific tests being performed are new and because none of these drugs showed an overall survival advantage, it remains unclear how to use them. Does one test all patients with melanoma for BRAF to identify a few, or does one wait until first line therapies stop working? Should BRAF or ALK testing be routinely performed and what are the cost implications of that strategy? Is this a step toward personalized medicine and what place does it take in the commonly accepted algorithms? All these remain unanswered questions that, with the current state of knowledge, relate more to the philosophy of medical care than to evidence based medicine.