Combination treatment improves the overall survival of patients suffering from melanoma with brain metastases

Combination treatment with immune checkpoint inhibitors nivolumab and Ipilimumab has shown overall survival for patients suffering from malignant melanoma that has spread to the brain, according to Phase II study results published today in The Lancet Oncology by researchers from The University of Texas MD Anderson Cancer Center.

Final results from the CheckMate 204 study confirm durable responses from the combination therapy -; which was made the first-line standard of treatment for this patient population based on the Phase II study results with an overall survival rate of 71.9% in asymptomatic patients after three years. 92% of those who received treatment within 12 weeks experienced overall survival. In patients with diagnosed brain metastases that are symptomatic or those receiving corticosteroid therapy were less, but they remained durable and had 36.6 percent overall survival.

Combination immunotherapy can trigger an intracranial reaction that can have a lasting impact on survival of patients with melanoma that has spread to their brains. This treatment offers a possibility of long-term survival for patients with a historically poor prognosis.”

Hussein Tawbi, M.D., Ph.D., the lead author,professor of Melanoma Medical Oncology and co-director of the Brain Metastasis Clinic at MD Anderson

40% of patients with stage IV melanoma have brain metastases after diagnosis and 75% of them develop metastatic brain disease at some point. Before the introduction of this combination the survival rate of one year for patients suffering from melanoma brain metaastases was about 20%.

The primary endpoint was intracranial clinical benefits rate. This was defined as partial and complete responses and stable disease lasting up to six months and stable disease. The investigator-assessed clinical benefit rate was 57.4% and objective response rate was 53.5% in asymptomatic patients. These results are similar to responses rates in metastatic melanoma patients with no brain metastases.

The investigator-assessed clinical benefit and objective response rates were both 16.7% in symptomatic patients. The rate of progression-free survival in the intracranial region was 3.5% in symptomatic patients and 5.1 percent in asymptomatic.

Responses were also evaluated using blinded independent central review (BICR) which is recommended for studies that evaluate cancer drugs in patients with central nervous system metastasis. Overall, the BICR and investigator assessments showed a high concordance.

Patients who did not respond to the treatment had a high overall survival rate, which the researchers suggest could be due to the subsequent radiation or systemic therapy . This could indicate that response to combination immunotherapy isn’t completely or accurately measured by current imaging techniques.

Tawbi said that “these results show that combination immunotherapy is effective and should be considered a first-line option for patients suffering from head metastases of melanoma.” “The study also shows that there are still effective options available for patients with symptoms of disease. We have the potential to improve the lives of the patients by finding ways to eliminate the need to take steroids.

The single-arm study began with the enrollment of patients suffering from brain metastases caused by melanoma (Cohort A) and was later modified to allow enrollment of patients with neurological symptoms or corticosteroid usage at baseline (Cohort B) which is commonly prescribed to treat symptoms in patients suffering from brain metastases.

A total of 101 patients were enrolled to Cohort A and 18 patients to Cohort B across 28 study sites in the United States. The median follow-up period was 34.3 months in Cohort A and 7.5 months in Cohort B. Patients in Cohort A had a median age of 59, and were 67.3% male and 98% white. Patients in Cohort A had a median of 59.5 years, and were 72.2 percent white and 94.5 percent black. Patients received Ipilimumab and Nivolumab every 3 weeks for 4 doses. Then the maintenance phase of Nivolumab was given every two weeks for up 2 years.

There were no new safety concerns, and the toxicities of the combination were comparable to previous trials in advanced patients with melanoma with no brain metastases. In Cohort A, 55.4% of patients suffered from grade 3 or 4 adverse effects related to treatment, leading to discontinuation of treatment in 28.7 percent. In Cohort B, 66.7% had grade 3 treatment-related adverse events, whereas 16.6 percent quit treatment. Cohort B did not experience any events of grade 4.

Colitis, pituitary inflammation and diarrhea and elevated liver enzymes were among the most frequently reported adverse reactions from treatment. The immune system is responsible for hepatitis, hyperthyroidism and rash. One patient died due to myocarditis caused by treatment was previously published.

“Combination immunotherapy is a toxic treatment, and one of our next areas of research is to develop treatments that are less harmful to patients but still effective,” Tawbi said. “Historically many patients suffering from brain metastases have been left out of clinical trials. We have now demonstrated that it is possible to conduct studies specifically for patients with this type of cancer.

MD Anderson’s multidisciplinary Brain Metastasis Clinic, which Tawbi co-directs with Frederick Lang, M.D. who is chair of Neurosurgery, and Jing Li, M.D., Ph.D., associate professor of Radiation Oncology, was established in the year 2019 to speed time to treatment and serve as a hub for conducting clinical trials for patients suffering from brain metastases.

The study was partially funded by Bristol Myers Squibb (BMS) and additional research support was provided by the National Institutes of Health. (P30 CA008748, and P30 CA016056). Tawbi was a consultant/advisor with BMS and received grant/research support. The paper contains a complete list of disclosures and co-authors.

Journal reference:

Tawbi H.A., and others. (2021). Long-term outcomes for patients with brain metastases from melanoma that are active treated using the drugs ipilimumab and Nivolumab. The Lancet Oncology.

Content Source:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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