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Ribociclib Plus Letrozole In Hormone Receptor-Positive, HER2-Negative Breast Cancer
In a phase III study of 700 postmenopausal women with hormone receptor-positive, HER2-negative recurrent or metastatic breast cancer receiving first-line letrozole, the addition of the CDK 4/6 inhibitor ribociclib improved progression-free survival (PFS). Ribociclib was associated with higher rates of grade 3 or 4 adverse events (eg, neutropenia, leukopenia, and elevated transaminases), though over 90 percent of patients were able to complete therapy. Because of the prolonged PFS but higher rate of toxicities, we offer the combination of CDK 4/6 inhibitors plus letrozole to patients with higher burdens of disease who are able to accept the increased risks of this treatment.
Primary Colorectal Tumor Location and Response to Cetuximab
Biologic agents with significant antitumor activity in metastatic colorectal cancer (mCRC) include bevacizumab and cetuximab, which is only active for RAS wild-type (RAS-WT) tumors. A major unanswered question has been the relative benefit of adding bevacizumab versus cetuximab to first-line cytotoxic chemotherapy for RAS-WT mCRC. A preliminary report from CALGB 80405, a prospective randomized trial of first-line chemotherapy plus either bevacizumab or cetuximab, suggests the importance of primary tumor location. Among patients with RAS-WT tumors, median survival was significantly better with cetuximab as compared with bevacizumab for those with left-sided primary tumors (36 versus 31 months), but not for right-sided primary tumors (17 versus 24 months). These data support a preference for bevacizumab rather than cetuximab as the biologic agent for initial treatment of mCRC with a right-sided primary tumor, even if RAS-WT.
Cabozantinib Versus Sunitinib in Metastatic Renal Cell Carcinoma
Cabozantinib has been shown to be superior to everolimus in previously treated metastatic renal cell carcinoma. In the CABOSUN trial, cabozantinib significantly increased progression-free survival compared to sunitinib in previously untreated patients with intermediate or high-risk renal cell carcinoma. Cabozantinib may provide an important option for previously untreated patients with metastatic disease, although it currently is approved only for patients who have received prior antiangiogenic therapy.
Whole Brain Radiation Therapy and Cognitive Function in Patients With Limited Number of Brain Metastases
Deferral of adjunctive whole brain radiation therapy (WBRT) in patients with a limited number of brain metastases who are eligible for surgery or stereotactic radiosurgery (SRS) has become more common over the last several years. This practice is supported by accumulating data from randomized trials showing that, although WBRT improves intracranial disease control, it does not appear to improve overall survival, and it is associated with early and delayed side effects that may worsen quality of life. A randomized trial of SRS plus WBRT versus SRS alone in 213 patients with brain metastases found that cognitive deterioration at three months was more common in patients who received WBRT (92 versus 64 percent), while overall survival was similar. Cognitive testing at 6 and 12 months and quality of life measures also favored SRS alone. Based on these results and other relevant studies, we suggest deferring adjunctive WBRT in most patients with a limited number of brain metastases. Such patients require serial neuroimaging after SRS alone to monitor for the development of new or progressive tumors.
Thrombotic Microangiopathy from Interferon
Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA. Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops.