Durable intracranial responses with nivolumab/ipilimumab

Melanoma patients with brain metastases can have a durable intracranial response with first-line nivolumab/ipilimumab, long-term results of CheckMate204 showed.

Brain metastases are a common complication of solid tumours and remain a major cause of disabling neurologic complications and death in patients with cancer. Surgical resection and stereotactic radiotherapy are highly effective treatments for local control. However, these treatments do not have any effect on the risk of the development of new brain metastases, on the control of extracranial disease, or on overall survival (OS).

The open-label, phase 2 CheckMate204 trial (NCT02320058) evaluated efficacy and safety of nivolumab/ipilimumab as treatment in melanoma patients with brain metastases. Previous results showed clinically meaningful intracranial efficacy, concordant with extracranial activity, and a safety profile similar to that reported in patients with melanoma who do not have brain metastases [1]. Dr Kim Margolin (City of Hope, CA, USA) now presented 3-year response and survival outcomes of CheckMate204.

In this study, patients with metastatic melanoma and ≥1 nonirradiated brain metastasis 0.5–3 cm in diameter received 4 cycles nivolumab (1 mg/kg)/ipilimumab (3 mg/kg) every 3 weeks, followed by nivolumab (3 mg/kg every 2 weeks) until progression or unacceptable toxicity. The primary endpoint was intracranial clinical benefit rate (CBR), defined as the proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) ≥6 months. A total of 101 patients with asymptomatic brain metastases (cohort A) and 18 patients with symptomatic brain metastases (cohort B) were enrolled. Median follow-up was 34 months in cohort A and 7.5 months in cohort B.

For cohort A, 36-month intracranial progression-free survival (PFS) was 54%, and OS was 72%. Intracranial CBR was 57%; of patients with objective response, 85% had an ongoing response at 36 months. For cohort B, 36-month intracranial PFS was 19%, and OS was 37%. Intracranial CBR was 17%; of patients with objective response, 100% had an ongoing response at 36 months. The toxicity profile of nivolumab/ipilimumab for both asymptomatic and symptomatic patients with brain metastases was similar to that of patients without brain metastases.

“These results show durable 3-year PFS and OS rates for the asymptomatic cohort, supporting the use of first-line nivolumab/ipilimumab,” concluded Dr Margolin. “Patients with symptomatic brain metastases remain difficult to treat, but some can also derive long-term benefit from first-line nivolumab/ipilimumab.”

1. Tawbi HA, et al. N Engl J Med. 2018; 379:722-730.
2. Margolin KA, et al. CheckMate204: 3-year outcomes of treatment with combination nivolumab (NIVO) plus ipilimumab (IPI) for patients (pts) with active melanoma brain metastases (MBM). Abstract 039MO, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202115 February, 2024