Administered before targeted therapy, the combination of two immunotherapies markedly improves survival in people affected by advanced melanoma.
- Undertaken with 265 participants with metastatic melanoma, the phase III clinical trial was cut short because the results appeared earlier than expected.
- These results show that, compared to patients who received first-line targeted therapy, those who first received immunotherapy had a 20% higher overall survival rate at two years.
- Cancer progression-free survival was also improved by immunotherapy.
With nearly 80,000 new cases each year in France, skin cancers are the most frequent cancers. Among them, 15,400 melanomas are identified every year, or 10% of skin cancers. They can either come from the cancerous transformation of a mole, or appear on healthy skin.
When detected early, this serious form of cancer can be effectively treated with surgery and, in recent years, with immunotherapy. A phase III randomized clinical trial titled DREAMseq has further supported the positive effects of immunotherapy in addition to targeted therapies. This trial was even interrupted prematurely because the final results appeared earlier than expected. It shows that immunotherapy is the best initial approach, even for people whose tumors have a mutation that could be treated with targeted therapies.
“The drug combinations tested in this trial all improve survival compared to previous standards of care, but we now know which combination should be given first to achieve maximum benefit for the vast majority of our patients. says Dr. Michael Atkins, a physician at Georgetown Lombardi Comprehensive Cancer Center. This trial should provide clearer guidance to clinicians on when to administer which treatments.”
An increase in the two-year overall survival rate
265 participants with metastatic melanoma participated from 2015 in the trial. They were randomly assigned to two groups: the first received an initial combination of drugs, followed by another combination if their cancer was resistant to the first.
The first drug combination included dabrafenib and trametinib. Taken in pill form, these two treatments target the effects of a mutation in the BRAF gene, which promotes tumor proliferation. Working together, the two targeted drugs inhibit the function of proteins associated with the BRAF mutation, resulting in direct destruction of tumor cells.
The other two-drug combination used the immunotherapy drugs ipilimumab and nivolumab. They have been administered intravenously and work by deactivating the cancer’s defense mechanisms, thereby releasing the body’s anti-tumor immunity.
The results of the trial were sufficiently definitive for the trial to be stopped and reported early. They show that the two-year overall survival rate of people who first received immunotherapies was 72%, compared to 52% for those who first received targeted therapies. Progression-free survival, that is, when the cancer is stable or improving, was also in favor of people who had started receiving the immunotherapies.
Further tests needed
However, one conundrum remains: some patients did not respond well to the initial immunotherapy treatments, and the switch to targeted therapies did not work either. “We are focused on trying to determine why there was no benefit for this small group of patients”points out Dr. Atkins.
The excellent results obtained during the trial, however, lead the researchers to believe that all patients with metastatic melanoma and who do not have other complicating factors should now be treated first with immunotherapy. They now want to determine which immunotherapy regimen is the best initial treatment for metastatic melanoma.
