Elisabeth Livingstone, MD, University Hospital Essen, Essen, Germany, discusses results from the phase 2 ImmunoCobiVem trial which investigated whether an early switch from targeted therapy to immunotherapy improves survival outcomes for patients with advanced BRAF V600-positive melanoma.

Dr Livingstone concluded, “All we can say is that, if you switch [patients] from targeted therapy to immunotherapy prior to progression, you have to expect a high rate of tumor progression on immunotherapy. However, it might induce a better long-term control, better long-term overall survival.”

Transcript:  

Hello everyone, my name is Elisabeth Livingstone, I'm from the Department of Dermatology at Essen University Hospital in Germany. At ESMO this year, 2024 in Barcelona, we were able to demonstrate the final results of the ImmunoCobiVem trial. 

ImmunoCobiVem is a trial for patients with BRAF-mutant melanoma and it's an international, multicenter, randomized trial. The purpose of ImmunoCobiVem is to investigate whether a short run-in with targeted therapy and switch to immunotherapy is more inducing and more durable tumor control than continuous targeted therapy. 

In this trial, 180 patients were started on vemurafenib and cobimetinib for 3 months and after those 3 months were reassessed and those patients who had achieved at least stable disease were then randomized to receive either continuous targeted therapy or to be switched to immunotherapy. Immunotherapy in this case was the PD-L1 antibody atezolizumab. The primary end point of the trial was progression-free survival, so the first progression after the randomized phase. We could see that with the switch to the immunotherapy, we lost a lot of tumor control, the majority of patients receiving atezolizumab after the 3-month run-in with targeted therapy had rapid progression of the disease. They were then switched back to targeted therapy and could respond very well. Those patients who continued on targeted therapy were later on switched to immunotherapy and there we could see once you switch patients after they have progressed on targeted therapy, they again do not respond very well to immunotherapy. 

In conclusion, with the final analysis we could see that the progression-free survival was much shorter with those patients who were switched to immunotherapy but when we look at overall survival, those patients who were switched to immunotherapy rather early on then had better overall survival. The overall survival was not significantly better, but we had better 4- and 5-year overall survival rates with immunotherapy.

This means that if you start with targeted therapy, it might be an option to switch to immunotherapy, but only in very few patients will you then have durable disease control. We have to be aware of the fact that most patients will have rapid disease progression and that we then have to reinitiate targeted therapy again, to which the patients can respond. We know by now, [since] the trial was started in 2016, from doing said trial as the combo trial that it's always best to start patients on immunotherapy if you will want long, durable disease control. However, we have some of these patients who have a very rapid disease course with high LDH, high tumor burden where we might fear that we will not be able to induce a good enough, fast enough immune response to immunotherapy. In these patients, if we then start with targeted therapy, we can achieve a very rapid response and then can maybe consider to switch them to immunotherapy. However, we could not demonstrate who exactly these patients are, same as with the EBIN trial, it might be those patients with very high LDH [lactate dehydrogenase], but I think this is something that needs further investigation.

For the moment, all we can say is that if you switch them from targeted therapy to immunotherapy prior to progression, you have to expect a high rate of tumor progression on immunotherapy; however, it might induce a better long-term control, better long-term overall survival. With this, I would like to thank you for your attention.

Source: 

Schadendorf D, Gogas H, Sekulovic LK, et al. Early switch from targeted to immunotherapy in advanced BRAFV600-positive melanoma: Long-term OS and final PFS results of the randomized phase II ImmunoCobiVem trial. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA45