Gynaecological cancer: New targets and immunotherapy developments

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Published: 7 Jul 2023
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Dr Mark Shahin - Jefferson Health, Philadelphia, USA

Dr Mark Shahin speaks to ecancer about the most important abstracts that were presented at ASCO 2023 regarding gynaecological cancers. 

An important study in the area of cervical cancer was the abstract presented by Dr Marie Plante highlighting that in many early-stage cervical cancers, surgery can be de-escalated. This results in improved quality of life for patients without compromising the efficacy of the treatment.

Dr Shahin further talks about the MIRASOL study which can be a potential game changer for the future treatment of ovarian cancer in the platinum-resistant space.

Additionally, in ovarian cancer, a new agent by the name of luveltamab was presented by a group and the study was sponsored by Sutro Pharmaceuticals.

Dr Shahin also discusses a study in which primary ovarian cancer is treated with chemotherapy plus maintenance therapy using durvalumab, olaparib and bevacizumab.

He concludes by discussing the important studies in the area of endometrial cancer.



What was your talk about?

This morning’s presentation is going to review some of the most important abstracts that were presented at ASCO in 2023. I’ve divided it into three segments focussing on cervical and ovarian cancer as well as endometrial cancer. 

In the area of cervical cancer, the abstract that was presented from the Canadian group, led by Dr Marie Plante, really highlights that in many of our early-stage cervical cancers we can de-escalate the surgery. So, if the patients have limited disease, whether squamous cell carcinoma or adenocarcinoma, with less than 10mm of invasion, with tumours that are less than 2cm, a simple hysterectomy probably is sufficient and can be substituted for radical hysterectomy. This results in improved quality of life for our patients down the road and does not compromise their treatment efficacy.

In ovarian cancer the most important highlight that was presented, in my opinion, was a study done with mirvetuximab in platinum-resistant ovarian cancer. The name of the study was MIRASOL, the presentation was by Dr Kathleen Moore. This study randomised patients to first-line treatment for platinum ovarian cancer essentially between the investigator choice chemotherapy versus mirvetuximab. The findings demonstrated that the patients who received mirvetuximab had a 45% response rate but, more importantly, that their overall survival actually improved. There was no new safety data presented here and the overall survival was significant, it was actually about 16.5 months versus 12 months in the investigator choice treatments. Quality of life was improved because many of these patients did not experience hair loss or significant peripheral neuropathy.

So I believe that that study is potentially going to be game changing for the future and is going to set the new standard of care in ovarian cancer in the platinum-resistant space. Additionally in ovarian cancer there was an additional agent by the name of luveltamab presented by a group and the study was sponsored by Sutro Pharmaceuticals. This is another folic acid receptor alpha mediated ADC, or an antibody-drug conjugate. It was phase I data and it shows that in our patients with Frα low we still can get significant activity. So more of this to come in the future; I think it’s an exciting foray into the future.

The last study in ovarian cancer which I thought it was important to highlight is primary ovarian cancer treated with chemotherapy plus maintenance therapy using durvalumab, olaparib and bevacizumab. This is a complicated regimen for maintenance therapy, however, specifically in the very difficult to treat HRD negative population, it demonstrated that their progression free survival improved and the hazard ratio was 0.6. So a very significant contribution in a very difficult to manage disease today. Again, this was the first time we saw immunotherapy having an impact in ovarian cancer and there are a couple more studies also being performed with dostarlimab as well as pembrolizumab and those are going to mature probably within the next two years. It will be very interesting to see whether the findings are replicated in those studies as well in the future.

Within the area of endometrial cancer, really the main findings were the effect of dostarlimab added to chemotherapy in the treatment of advanced or recurrent endometrial cancer. This study was originally presented at the Society of Gynaecologic Oncology meeting in March but the investigators went back and wanted to see whether the investigator assessment and the blinded investigators had similar reporting of the findings. In both of the instances, whether you gave this combination to mismatch repair deficient patients or mismatch repair proficient patients, there was improvement in overall survival. 

An additional abstract that was presented looked at patient reported outcomes in this cohort and the patient reported outcomes in the patients who received dostarlimab or immunotherapy actually were improved and that’s because their disease was better controlled. So I think it’s going to set the stage for the introduction of immunotherapy in addition to chemotherapy in this population.

I finished my presentation by a section on tumour agnostic section and this has to do with the investigators who presented data on a trial called DESTINY-02. This trial looked at the use of trastuzumab deruxtecan and it highlighted the response of tumours in ovary, cervix, as well as endometrial cancers and some additional solid cancers to this agent. This agent is now currently in use in HER2-mutated breast cancer and it was interesting to focus and see whether it has activity in this population. The responses were very remarkable and we saw responses anywhere from 40-50% in, again, HER2 mutated ovarian cancer, endometrial cancer, as well as cervical cancer. This is going to set the stage for the introduction of this agent as a single-agent therapy in this space for patients who have failed other therapies.

So, all in all, a very exciting cohort of presentations that are going to have positive impact in our day-to-day practice.