1. Objective response rate was 35%, with 1 patient showing a complete response and 7 showing a partial response.

2. Most common adverse events included fatigue, anorexia, hand-foot syndrome, hypothyroidism, and mucositis.

Evidence Rating Level: 2 (Good)

Study Rundown: Cabozantinib’s benefit in non-clear cell renal cell carcinoma (ncRCC) has been previously documented. This study explored the use of cabozantinib (an inhibitor of multiple tyrosine kinase receptors) on patients with metastatic collecting duct carcinoma (mCDC), a rare type of ncRCC with a poor prognosis. Patients were only assigned to a treatment group, and were given cabozantinib until disease progression, onset of unacceptable toxic effects or withdrawal. The primary end point was objective response rate (ORR), defined by patients having a complete or partial response, and was found to be 35%. Median time to data censor was 11 months, median progression-free survival (PFS) was 4 months, and median overall-survival (OS) was 7 months. When indirectly compared to other first-line treatments for mCDC, cabozantinib yielded a higher ORR, and similar median PFS and median OS though there is caution in cross-trial comparisons. Adverse events of grades 1 and 2 occurred in all patients, notably including fatigue, anorexia, hand-foot syndrome, hypothyroidism, and mucositis. Adverse events of grade 3 were higher with cabozantinb than the other first-line therapies. Limitations to this study include the small sample size, predominantly male participants, and the fact that this study was only performed in Italy. It is also limited by its indirect comparison of cabozantinib and other first-line therapies. The strength of this study is that it provides a treatment option to mCDC, which normally has a poor prognosis. Overall, this study demonstrated that cabozantinib as a first-line therapy for patients with mCDC is hypothesis generating and warrants further studies.

Click to read the study in JAMA Oncology

Relevant Reading: Characteristics and treatment challenges of non-clear cell renal cell carcinoma

In-Depth [prospective cohort]: This phase II, single-arm clinical trial in Italy included 23 patients with mCDC. The ORR was 35% (95% confidence interval [CI], 16% to 57%), the median time to censoring was 11 months (95% CI, 0 to 22 months), the median PFS was 4 months (95% CI, 3 to 13 months), and median OS was 7 months (95% CI, 3 to 31 months). When indirectly compared to standard therapy regimen for mCDC (carboplatin plus gemcitabine), cabozantinib had a 9% increase in ORR and similar PFS and OS. Adverse events of grades 1 and 2 occurred in all patients, with the most common being fatigue (60%), anorexia (39%), hand-foot syndrome (30%), hypothyroidism (30%), and mucositis (30%). Adverse events of grade 3 occurred more with cabozantinib when indirectly comparing it to standard mCDC therapy +/- sorafenib. Overall, cabozantinib led to an ORR of 35% and may be a promising first-line treatment but will need more studies to further investigate.

Image: PD

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