Dr. Abhi Nair: Welcome back to the DISCO, the FDA’s Drug Information Soundcast in Clinical Oncology from the Oncology Center of Excellence. We are located in Silver Spring, Maryland, and during our soundcasts, we discuss recent FDA approvals of cancer drugs and therapies. We hope this information will help you in better understanding these approvals and how new drugs and therapies are benefitting cancer patients.
I’m Dr. Abhi Nair, a medical oncologist at the Oncology Center of Excellence, and I’m joined by my colleague Dr. Sanjeeve Bala, also a medical oncologist and a clinical team leader at FDA.
Dr. Sanjeeve Bala: Hi everyone. Thanks for joining us.
AN: Today in the DISCO, we will discuss the approval of sunitinib, marketed as Sutent, for the adjuvant treatment of adult patients who are at high risk for the development of recurrent renal cell carcinoma following a nephrectomy. Just to remind the listeners, sunitinib was already approved in January of 2006, for the treatment of advanced renal cell carcinoma and this recent approval moves it to an earlier line of treatment in this disease. Sanjeeve will now give us a background on adjuvant treatment of renal cell carcinoma.
SB: Thanks, Abhi. Patients with renal cell carcinoma who have large tumors or lymph node positive disease are at high risk of recurrence following surgical resection. For patients with node-positive disease, 5-year disease-specific survival ranges from 0 to 32%, so there’s an unmet need for adjuvant options that can reduce this risk. Until now, there were no FDA approved adjuvant treatment options for high-risk patients with renal cell carcinoma after surgical resection.
SB: Abhi, let’s dig into the data. Let’s hear about the trial that led to approval.
AN: Sutent was approved for this indication based on the results of the multi-center, international, double-blind, placebo-controlled trial called S-TRAC. S-TRAC was conducted in 615 patients with a high risk of recurrent renal cell carcinoma following nephrectomy.
SB: How did they define the population at high risk of recurrence?
AN: Sanjeeve, high-risk patients were defined as T3-4, N negative (N0) to Nx disease or node-positive clear cell carcinoma patients. These patients were randomized 1:1 to receive 50 mg sunitinib once daily, 4 weeks on treatment followed by 2 weeks off, or placebo.
SB: I think we’re ready to hear those trial results.
AN: Sure. Median disease-free survival for patients taking sunitinib was 6.8 years compared with 5.6 years for patients receiving placebo, for a statistically significant hazard ratio of 0.76. At the time of disesase-free survival analysis, overall survival data were not mature.
SB: Abhi, I recall that this application was discussed at an Oncologic Drugs Advisory Committee meeting in September 2017. What was the main issue discussed at the ODAC?
AN: Sanjeeve, the main item discussed was how the results of the S-TRAC study differed from another trial called ASSURE that failed to detect an improvement in disease-free survival in this disease setting. In ASSURE, the hazard ratios for the comparison of sunitinib and placebo were 1.02 for disease-free survival and 1.17 for overall survival, favoring placebo. No difference in overall survival has been observed in S-TRAC. During the ODAC, FDA highlighted that the differences in patient population and sunitinib dose prevented a conclusion regarding differences in the results of S-TRAC and ASSURE, but S-TRAC did demonstrate a statistically significant and substantial difference in disease-free survival. Disease-free survival as an endpoint in the adjuvant setting was also discussed during the ODAC, and FDA noted that the magnitude of benefit seen in disease-free survival here was similar to that seen in other adjuvant approvals.
SB: All right, what safety findings appeared during the conduct of the S-TRAC trial?
AN: No new safety signals were identified for the use of sunitinib in the adjuvant setting, but data on long-term toxicities is limited. Twenty-eight percent of patients permanently discontinued sunitinib in the S-TRAC trial and 61% required a dose reduction or interruption. So, although the toxicity of one year of sunitinib was substantial, it may be acceptable in patients who are at a high risk of recurrence. Detailed safety information is available in the product label.
SB: This is an interesting new option for the adjuvant treatment of patients at high risk of recurrence after resection of renal cell carcinoma. Based on the data, patients and prescribers should have a detailed discussion of the pros and cons of this choice along their treatment path. Abhi can you summarize the three main take-away points from this DISCO?
AN: Sure, Sanjeeve. The three main take-away points are: 1) sunitinib is approved for the adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma following a nephrectomy; 2) the approved dose is 50 mg orally once daily, 4 weeks on treatment followed by 2 weeks off, for nine 6-week cycles. It can be taken with or without food; and 3) the toxicity profile of sunitinib was similar to that seen in the advanced renal cell carcinoma setting and prescribers need to weigh these risks against each patient’s potential benefit.
AN: You can find more details in the prescribing information, which is also online at Drugs@FDA. For a transcript with a link to the prescribing information and the multidisciplinary team of FDA experts who conducted the review, visit the FDA Oncology Center of Excellence DISCO website at fda.gov/DISCO.
SB: And so, to our listeners, are there other FDA oncology drug approvals that you want to hear about? Leave us your questions and comments on Twitter @FDAOncology. Or, send us an email! Our email address is FDAoncology@fda.hhs.gov. I’m Sanjeeve Bala, thanks for joining us at this episode of the DISCO.
AN: And until next time at the DISCO, I’m Abhi Nair.
This Drug Information Soundcast in Clinical Oncology was developed by Abhilasha Nair, Sanjeeve Bala, Sundeep Agarwal , V. Ellen Maher, Kirsten B. Goldberg, and Richard Pazdur, of the Oncology Center of Excellence and the Office of Hematology and Oncology Products. Steven Jackson of the Division of Drug Information was the sound producer.
Reviewers for this Supplemental New Drug Application were:
Regulatory Project Manager: Jeanette Dinin
Nonclinical: Eias Zahalka, Todd Palmby
Clinical Pharmacology: Salaheldin Hamed, Pengfei Song
Clinical: James Xu, Sundeep Agrawal
Statistical: Laura Fernandes, Jiaxi Zhou
Cross-Disciplinary Team Leader: V. Ellen Maher
Division Director (OHOP/DOP1): Julia Beaver