ASCO 2019: First-Line Immuno-oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International mRCC Database Consortium

Chicago, IL (UroToday.com) In metastatic renal cell carcinoma (mRCC) several first-line immuno-oncology combination therapies have been demonstrated to have improved outcomes vs. sunitinib monotherapy. Comparative data between ipilimumab/nivolumab (IPI/NIVO) and immune-oncology-VEGF (IO-VEGF) inhibitor combinations are limited. Additionally, the use and effectiveness of second-line therapies following progression on first line immune-oncology combination treatments remains unknown.

In the presented study, the authors used the IMDC dataset to identify patients treated with first-line IPI/NIVO or any IO-VEGF inhibitor combination and compared outcomes between the two groups. Patients treated as part of a clinical trial were not excluded.

The outcomes of interest included:
  • Response rate to 1st and 2nd line therapy
  • 1st and 2nd line time to treatment failure
  • Time to next treatment
  • Overall survival

Multivariable Cox regression analysis was performed to control for imbalances in IMDC risk factors.

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A total of 188 patients with mRCC treated with first-line immune-oncology combination therapy were included. Table 1 demonstrates the patient characteristics. Of these, 113 patients were treated with IO-VEGF combinations, and 75 patients were treated with IPI/NIVO. The majority of 2nd line treatments (86%) were VEGF-based treatments (Table 2).

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Table 3 demonstrates the response rate, time to treatment failure, and overall survival in the groups. Figure 1 and Figure 2 show the Kaplan-Meier curves for overall survival and time to treatment failure compared between the treatment groups. The graphs demonstrate no statistically significant difference between the various treatments. The outcomes were similar when restricting the cohort to IMDC intermediate and poor-risk patients only.

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In patients receiving 2nd line VEGF-based therapy, 2nd line response rate was greater in those who received IPI/NIVO, though 2nd line time to treatment failure was not significantly different (Table 4).

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The authors concluded that there does not seem to be a superior 1st line immune-oncology combination strategy in mRCC, as IO-VEGF inhibitor combinations have comparable response rates, time to treatment failure, time to next treatment and overall survival to IPI/NIVO. 2nd line treatments were primarily VEGF-based, for which activity was demonstrated. Within this cohort, 2nd line response rates were greater in those who received IPI/NIVO initially, though there was no difference in 2nd line time to treatment failure. Lastly, the use of immune-oncology treatment combination following 1st line IO-VEGF combination treatment was uncommon. Of those who received 2nd line Immune-oncology treatment, the majority experienced progressive disease as best response.

Presented by: Shaan Dudani, MB, ChB, Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA