Mirvetuximab soravtansine shows promise in FRα-positive, platinum-sensitive ovarian cancer
Dr Angeles Alvarez Secord - Duke Cancer Center, Durham, USA
The PICCOLO study is a global phase II open-label study of mirvetuximab in those with platinum-sensitive ovarian cancer and heavily pretreated. Specifically, in the study patients had to have had at least two prior lines of therapy. They also had to have FRα high expression and that was based very specifically on their PS2 positive intensity score in ≥75% of the viable tumour cells.
In terms of the patient population, 302 patients were screened for the study, 44% were eligible based on their FRα high expression. In the demographics it’s very important to note that 38% had had at least three prior lines or more, 81% previously treated with a PARP inhibitor and about 74.7% of those patients had progressed on that PARP inhibitor. So this is a really important population for us to understand in this new era that we’re living in where a lot of our patients do receive a PARP inhibitor in the front-line setting what is going to be their response to subsequent therapies. In addition, over 60% of patients had previously been treated with bevacizumab and 54% had a platinum-free interval that was ≤ 12 months.
What were the findings?
What we found is really exciting. I just want to share with you first the primary endpoint here was investigator assessed objective response rate and a key secondary endpoint was the duration of response. In terms of what we found, 79 participants enrolled in the study and of those participants all of them were evaluable for the efficacy endpoint. In terms of the objective response rate 51.9% of patients responded and 7% of patients had a complete response.
What was really exciting when you look at the waterfall plot is the depth of the responses and breadth of responses. Almost every patient on the study derived clinical benefit.
One of the things that we did was a subgroup analysis across the various different groups to evaluate the response rates of mirvetuximab in these smaller subsets. We do have to be somewhat cautious because some of these smaller groups did have small numbers that limit our ability to interpret the findings fully. However, I want to share with you some of the promising findings.
In patients who had a BRCA mutation or in those patients who had not previously been treated with a PARP inhibitor the objective response rates were over 70%. In patients who received a prior PARP inhibitor and progressed on that PARP inhibitor the response rate was 45.8% and the median duration of response in that group of patients, that I think is going to be very difficult to treat, was over 7 months. So I’m very excited about the findings of the high levels of response in all of these groups but very enthusiastic about our findings specifically in those patients who received a prior PARP inhibitor and progressed on that treatment.
What toxicities were experienced?
There were no new safety signals, in fact the toxicity shown here was very similar to prior studies and shows that differentiated safety profile that mirvetuximab has which is very mild – for the most part gastrointestinal toxicities, neurosensory side effects as well as reversible ocular events.
What impact could these findings have?
I’m really hopeful that the PICCOLO trial will lead to use of this novel therapeutic option for patients with heavily pretreated platinum sensitive disease who have high FRα expression. Being able to provide these patients with a single agent effective therapy that has a good, tolerable profile is incredibly important. As I mentioned, most of these patients have been heavily pretreated; the more you receive carboplatin the more likely you are to have toxicity, especially hypersensitivity reactions and it can be more challenging for the patients to receive the dosages that may have the best benefit for them.
