We have to remember that gestational trophoblastic tumours are rare tumours developing in the placenta of young patients during pregnancy. The standard treatment relies on chemotherapy, either single agent chemotherapy for low risk disease or polychemotherapy for high risk disease. But outside chemotherapy there is no innovative treatment available for this disease. So the idea was to see if we could develop some new approach outside chemotherapy for our GTTs resistant to chemotherapy because if chemotherapy is very effective it is also toxic with sometimes very important immediate and long-term side effects. There are patients who are resistant to chemotherapy so there was really a need for a new treatment.
We had a strong rationale for thinking that monotherapy and especially avelumab would be effective in GTT patients so that’s why we designed the academic TROPHIMMUN trial. It’s a phase II trial where patients with resistance to chemotherapy are treated with avelumab given IV every two weeks. The primary endpoint is the rate of patients with hCG normalisation that involved avelumab discontinuation. What we wanted to see is how many of these patients would present any relapse despite treatment discontinuation. So avelumab was continued until normalisation of serum hCG and then continued for three consolidation cycles and it was stopped then.
The results we presented were about cohort A where these were patients resistant to single agent chemotherapy. There is also cohort B which is ongoing with patients with resistance to polychemotherapy. We reported the results of cohort A.
We enrolled 17 patients, out of them 15 patients were treated and assessable. Out of these 15 patients 8 patients had hCG normalisation with avelumab and with a 29 month follow-up none of them have relapsed despite the avelumab discontinuation meaning these patients are likely to be cured. That means that actually it would be a successful hCG normalisation in about 53% of patients.
There are two remarkable outcomes. The first one is out of these 15 patients five of them should otherwise have been treated with polychemotherapy because they had high hCG or because they were resistant to both standard single agent chemotherapies. These five patients were successfully treated with avelumab so they really could be prevented from the very high toxicity of a polychemotherapy regimen so it’s very important.
The second very interesting result is that one of the patients who was successfully treated with avelumab wanted to be pregnant so she was allowed to stop contraception one year after avelumab discontinuation and because her hCG was normal. Actually as soon as she stopped contraception she developed a pregnancy which was perfectly normal and she delivered a very healthy baby. So that’s very interesting because this was the first report of a normal pregnancy after successful previous treatment with immunotherapy. So of course it’s not evidence about the lack of consequences on subsequent fertility but it’s very reassuring data.
Finally, the safety was very good. Patients presented with very few side effects, much better than chemotherapy I can tell, based on my experience. So we’re happy with that. So, in conclusion, it shows that, first, it’s possible to make a trial in such a rare disease because we have the French Gestational Trophoblastic Centre with a network of centres and where we could perform the trial, so that it was feasible. Secondly, it’s a proof of concept trial which confirms that immunotherapy is very promising in these tumours. Moreover, it shows that about 50% of patients with resistance to single agent chemotherapy would be successfully treated with avelumab. They normalised hCG and none of them relapsed so that’s very nice, suggesting they are likely to be cured. So probably it’s an option for patients who have resistance to single agent chemotherapy but especially those who should be treated with polychemotherapy because we could avoid in these patients a very high toxicity of polychemotherapy.