Martin H. Voss, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses results of a randomized phase I/II trial (NCT02118337) looking at the combination of MEDI0680 and durvalumab (Imfinzi) versus nivolumab (Opdivo) in metastatic renal cell carcinoma (mRCC).

For the phase I/II trial, investigators set out to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab compared with nivolumab monotherapy in immunotherapy-naïve patients with metastatic clear cell renal cell carcinoma.

However, no significant difference in overall response rate, progression-free survival, or overall survival was observed between the 2 arms of this trial, says Voss. Furthermore, no subgroups appeared to derive additional benefit from the combination versus the single-agent, explains Voss.

Results from a safety analysis showed that grade 3/4 treatment-related adverse events (TRAEs) occurred in 26% of patients who received the combination versus 19% who received nivolumab. Furthermore, 12% of patients discontinued treatment as a result of TRAEs compared with 5%, respectively, Voss concludes.

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Martin H. Voss, MD, discusses results of a randomized phase I/II trial looking at the combination of MEDI0680 and durvalumab (Imfinzi) versus nivolumab (Opdivo) in metastatic renal cell carcinoma.
 

Dr. Voss on Phase I/II Trial Data of MEDI0680/Durvalumab Versus Nivolumab in mRCC

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, explains the case for neoadjuvant therapy in the treatment of kidney cancer.

Voss says that there is debate around whether there is merit to using neoadjuvant therapy in patients with kidney cancer who have non-metastatic disease versus adjuvant therapy. One of the concerns with neoadjuvant approaches is that preoperative therapy with a systemic agent may delay surgery. Another concern is that there may be toxicities from neoadjuvant therapy that may get in the way of surgery.

Voss says that recent data suggest that these concerns are probably not well founded. Drugs that would be used as neoadjuvant treatment would not necessarily delay time of surgery, he adds, and even if they did—delaying surgery a few months is not likely to affect outcomes.

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, explains the case for neoadjuvant therapy in the treatment of kidney cancer.
 

Dr. Voss on the Case for Neoadjuvant Treatment in Kidney Cancer

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses treatment in the neoadjuvant setting for patients with kidney cancer.

There is a large body of data in the adjuvant setting using the medications that were developed in the metastatic setting. Almost all approved adjuvant agents have been in post-operative development, explains Voss.

In the neoadjuvant setting, there are many trials that have been testing tyrosine kinase inhibitors (TKIs). None of those trials have been randomized, so the outcome cannot be compared to surgery alone. The primary endpoint of these studies were surgical endpoints, such as operative feasibility, resectable disease, or shrinking primary tumors.

The FDA recently has approved cabozantinib (Cabometyx) for previously untreated patients with advanced kidney cancer, based on a meaningful improvement in progression-free survival versus sunitinib (Sutent) in the CABOSUN trial.

Dr. Voss Discusses Treatment in the Neoadjuvant Setting for Kidney Cancer

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the future of the clinical trial space for patients with kidney cancer.

According to Voss, collaboration is important for the neoadjuvant concepts that are being developed. It is important discuss systemic therapies in a surgical context and as a multidisciplinary effort.

The key to successful development of approaches is to have a multidisciplinary team involved, says Voss.

Dr. Voss on the Future of Clinical Trials for Kidney Cancer

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses neoadjuvant immunotherapy trials in renal cell carcinoma (RCC).

Given the data seen in the metastatic space, the field is moving toward immunotherapy-based approaches, says Voss. This is especially true for preoperative trials in non-metastatic disease.

The phase III PROSPER RCC trial (NCT03055013) is comparing nephrectomy with or without nivolumab (Opdivo), and is currently accruing in the United States. 

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses neoadjuvant immunotherapy trials in renal cell carcinoma (RCC).
 

Dr. Voss Discusses Neoadjuvant Trials of Immunotherapy in RCC

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses a phase II study examining bevacizumab combined with CRLX101 for the treatment of patients with advanced renal cell carcinoma (RCC).

CRLX101 has been shown in pre-clinical studies to inhibit the HIF pathway. The majority of patients with clear cell RCC lose function of VHL and increase regulation of HIF, Voss explains. By treating these patients with antiangiogenic agents, HIF levels can be increased further. Voss predicts that a HIF antagonist can have efficacy against tumor biology, but can also overcome antiangiogenic inhibitor-mediated treatment resistance.

The ongoing phase II study is randomizing patients with two or three prior lines of VEGF-targeted therapy to receive bevacizumab plus CRLX101 to physician's choice of therapy. Prior immunotherapy is permitted. The trial design is interesting, Voss explains, because there is no similar regimen approved in the third- or fourth-line setting.

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses a phase II study examining bevacizumab combined with CRLX101 in patients with advanced renal cell carcinoma.

Dr. Voss on Bevacizumab With CRLX101 in Advanced RCC

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses early efficacy signals in the phase I/II DART study.

The study compared dalantercept plus axitinib with placebo plus axitinib for patients with advanced clear cell renal cell carcinoma. Median progression-free survival (PFS) was approximately 8 months across the entire population. Regarding the dosage level that will be used in the phase II setting, the median PFS has not yet been reached.

In comparing these results to phase III data involving axitinib alone in pretreated TKI patients, Voss says the DART study results are promising. Median PFS in the earlier study was less than 5 months.

Voss says the DART data should be taken cautiously, and not compared across other clinical trials. However, he adds the efficacy signals are helpful in determining if the trial is worth moving forward to phase II and III settings. 