ASCO 2021: Safety and Efficacy Outcomes with Nivolumab plus Ipilimumab in Patients with Advanced Renal Cell Carcinoma and Brain Metastases: Results from the CheckMate 920 Trial

(UroToday.com) Many patients with renal cell carcinoma (RCC) present with de novo metastatic disease and an appreciable proportion of patients with an initial diagnosis of localized disease subsequently develop advanced or metastatic RCC after surgical treatment. Metastasis to the central nervous system is reported in 3-17% of patients with advanced disease. Patients with untreated brain metastasis typically have a poor prognosis, with a median overall survival (OS) of < 1 year, short progression-free survival (PFS), and neurological symptoms. Combination therapy with nivolumab plus ipilimumab has demonstrated long-term efficacy and tolerability in patients with previously untreated advanced RCC.1 Previous phase 3 clinical trials of patients with advanced or metastatic cancers have mostly excluded patients with brain metastases. CheckMate 920 is a prospective, US community-based, multi-arm, ongoing phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in patients with previously untreated advanced RCC and clinical features mostly excluded from phase 3 trials, and therefore is an unmet medical need. At the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Hamid Emamekhoo and colleagues presented updated safety and efficacy results for the cohort of patients with advanced RCC of any histology and brain metastases from CheckMate 920.


In CheckMate 920, patients with previously untreated advanced/metastatic advanced RCC of any histology, with asymptomatic brain metastases (not currently receiving corticosteroids or radiation), and Karnofsky performance status ≥ 70% were assigned to treatment with nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks × 4 doses followed by nivolumab 480 mg every 4 weeks for ≤ 2 years or until disease progression/unacceptable toxicity. The study design schema is as follows:

ASCO_CheckMate_920.png

The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events within 100 days of the last dose of study drug. Key secondary endpoints included PFS and objective response rate by RECIST v1.1 (both per investigator). Exploratory endpoints included OS.

Among 28 treated patients with brain metastases, 85.7% were men; median (range) age was 60 (38–87) years, and 14.3% had sarcomatoid features. With 24.5 months minimum follow-up of the 28 patients enrolled, the median duration of therapy (range) was 3.4 (0.0–23.3) months for nivolumab and 2.1 (0.0–3.3) months for ipilimumab. No grade 5 immune-mediated adverse events occurred. Grade 3–4 immune-mediated adverse events by category were diarrhea/colitis (7.1%), hypophysitis (3.6%), rash (3.6%), hepatitis (3.6%), and diabetes mellitus (3.6%). Of the 25 patients who were evaluable for objective response rate, the objective response rate was 32.0% (95% CI, 14.9–53.5). No patients achieved complete response, 8 achieved partial response, and 10 patients had stable disease. Median time to response (range) was 2.8 (2.4–3.0) months. Median duration (range) of response was 24.0 (3.9–NE) months, and 4 of 8 responders remain without reported progression. Of 28 patients, 7 (25%) had intracranial progression. Median PFS was 9.0 (95% CI, 2.9–12.0) months:

ASCO_RECIST_v1.1.png

and median OS was still not reached (95% CI, 14.1 months–NE):

ASCO_CheckMate_920_RCC.png

Dr. Hamid Emamekhoo concluded his presentation of the CheckMate 920 trial with the following take-home messages:

  • With longer follow-up, the safety profile of nivolumab plus ipilimumab for patients with previously untreated advanced RCC and brain metastases was as expected, and no new safety signals have emerged
  • Consistent with the results from the phase 3 CheckMate 214 trial,1 nivolumab plus ipilimumab continues to show encouraging antitumor activity, OS, and durable response
  • The results in this cohort support the hypothesis that patients with CNS metastases may be biologically similar to patients with non-CNS disease in their response to immunotherapy
  • Results from the CheckMate 920 trial add to the limited evidence and relative dearth of prospective or retrospective analyses that had evaluated outcomes in patients with RCC and brain metastases, a population with poor prognosis and a high unmet medical need

Clinical trial information: NCT02982954

Presented by: Hamid Emamekhoo, MD, University of Wisconsin School of Medicine and Public Health, Madison, WI

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021

References:

  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carinoma. N Engl J Med 2018;378(14):1277-1290.
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