Immunotherapy Given Before Targeted Therapy

When a combination of two immunotherapy medications is given before a combination of two targeted therapies, it can increase the chances of survival of patients suffering from advanced melanoma. If needed more persons with advanced melanoma survive for two years or longer than when targeted therapies are given first.

The discovery stems from a clinical experiment that was prematurely terminated because definitive results emerged sooner than expected. It gives good evidence on how to effectively treat individuals with melanoma with a specific mutation: immunotherapy is the preferable first line of treatment even if the tumors have a mutation that could be treated with targeted medicines.

Immunotherapy Given Before Targeted Therapy

“The drug combinations tested in this trial all improve survival compared to prior standards of care but we now know which combination should be administered first to achieve maximum benefit for the vast majority of our patients,” says Atkins. “This trial should provide clearer guidance to clinicians on when to administer particular treatments.”

This is a welcome development in the field of immunotherapy as it helps doctors to provide better treatment. Further developments are expected in the next few months in this regard.

Immunotherapy Given Before Targeted Therapy

Each regimen had its unique approach to melanoma treatment. The medications dabrafenib and trametinib which are taken as pills were used to address the consequences of a mutation in the BRAF gene. Everyone in the study had melanoma with the BRAF V600 mutation which is known to promote tumor growth. The two targeted medications work together to block the activity of the proteins linked to the BRAF mutation resulting in direct tumor cell death.

Beginning in 2015, 265 trial participants with metastatic melanoma were randomly assigned to one of two groups: one received one treatment combination followed by the other if the first combination failed to work.

The immunotherapy medications ipilimumab and nivolumab were used in the other two-drug combination. They were administered intravenously and worked by weakening cancer’s defense mechanisms allowing the body’s antitumor immunity to take over.

Other trial outcomes are intriguing but they raise questions that will require further investigation in future analyses or research. Overall response rates which reflect whether patients had a partial or complete response to the medications were similar across all drug administration scenarios except for those who received targeted therapies first and then immunotherapy indicating that immunotherapy may not operate effectively following targeted therapy.

With 59 percent of patients having been on the experiment for two years, the results were conclusive enough that the trial was halted and disclosed early. People who first received immunotherapies had a 72 percent two-year overall survival rate compared to 52 percent for those who first received targeted therapies. Progression-free survival or survival, while the cancer is stable or improving, was also favoring those who started immunotherapies.

“One conundrum in the data showed that some patients don’t do well on initial immunotherapy treatments and for some reason switching to targeted therapies did not help,” says Atkins. “We are focusing on trying to determine why there was no benefit for this small group of patients.”

Given the apparent benefit of starting with immunotherapy first which is not contingent on having a BRAF mutation, the researchers believe that all patients with metastatic melanoma who do not have other complicating issues should now receive immunotherapy first. What this study doesn’t address is which immunotherapy regimen is the most effective as a first-line treatment. Other clinical trials are still looking at this subject.

“While this trial focuses on melanoma it could have significant implications for the treatment of other forms of cancer where immunotherapies are increasingly part of treatment regimens,” says Atkins.

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