Ovarian cancer: more weapons against recurrences

Ovarian cancer: the difficult management of platinum-resistant cancers

Ovarian cancer most often results from malignant degeneration of the epithelial cells that line the ovary (outer layer of the ovary called the epithelium). This cancer most often develops without any particular symptoms. In fact, its diagnosis is therefore difficult and is often made late.

The treatment is primarily based on surgery to remove the tumor, if possible in its entirety. Depending on the extent of the cancer, the surgeon may also decide to remove the uterus, the fallopian tubes, the other ovary, as well as other organs close to the ovaries. Most often, chemotherapy is given after surgery to reduce the risk of recurrence (this is called adjuvant chemotherapy). Targeted therapies (bevacizumab – Avastin ®) have offered a complementary option since 2014.

But when cancers become resistant to chemotherapy using platinum derivatives, other chemotherapies have shown limited activity and considerable toxicity. There has been no news for this disease since 2014, when bevacizumab was introduced in combination with chemotherapy.

But in the face of these particularly formidable cancers, two studies offer new hope.

A conjugated antibody, a real targeted missile

Even if several studies had already made it possible to apprehend the potential of these new drugs (in particular Enhertu against ER2+ breast cancers), the ASCO 2023 World Congress confirms the hopes raised by conjugated antibodies. These drugs are veritable guided missiles against the tumour. They combine targeting of the cancerous cell (generally a specific receptor on its surface) with very toxic chemotherapy delivered at a tiny dose. The result: selective destruction of cancer cells. Even if these therapies are not completely devoid of side effects, they make it possible to deliver chemotherapy directly to the level of the cancerous cell without the side effects of systemic chemotherapy and with greater efficiency.

Mirvetuximab soravtansine (marketed as Elahere ® ) targets the folate receptor alpha, which is overexpressed on a variety of epithelium-derived cancer cells. When the drug binds to this receptor, it delivers chemotherapy into the cancer cell, which dies.

In this study, 453 women with platinum-resistant high-grade epithelial cancer of the ovary, primary peritoneum, or fallopian tubes (with elevated expression of folate receptor alpha – a predictive marker of efficacy of this drug found in nearly 90% of ovarian cancers) benefited from this drug, whether or not they received bevacizumab upstream.

Results :

• With an average follow-up of approximately 13 months, in the group of 281 women previously treated with bevacizumab, progression-free survival (PFS – time to non-progression of the disease) was improved by 36% and overall survival (OS) by 26 % for women who received mirvetuximab soravtansine compared to standard chemotherapy chosen by the doctor.
• In the group of 172 women who had never received bevacizumab, PFS was 34% better and OS 49% better for women who received mirvetuximab soravtansine compared to standard chemotherapy chosen by the physician.

Better efficiency with fewer side effects. “Mirvetuximab soravtansine has fewer serious side effects, especially those that may lead to treatment discontinuation, compared to standard chemotherapy regimens for patients with platinum-resistant ovarian cancer. This, together with the overall survival benefit, demonstrates progress and offers hope for these patients.“, said ASCO expert Prof. Merry Jennifer Markham.

“Mirvetuximab soravtansine is undergoing accelerated approval by the US authorities -FDA-, so we hope that these trial results will lead to a rapid formal approval. But more importantly, it opens the door to the drug’s global availability outside the United States, where expedited approval is not an option.said Kathleen N. Moore, associate director of clinical research at the University of Oklahoma Stephenson Cancer Center. Other ongoing studies are evaluating this same drug for earlier stages of the disease.

CHIP, a heated chemotherapy bath right after surgery

In these same patients, a French study presented as part of ASCO 2023. It aims to confirm the usefulness of HIPEC, an acronym for Intra-Peritoneal Hyperthermic Chemotherapy. The principle of this technique is simple: the visible disease is removed by surgery while the disease invisible to the naked eye is destroyed by heated chemotherapy placed directly in the peritoneal cavity, just after the surgical procedure. A technique that Pr. Jean-Marc Classe already told us about in 2016.

He is also the one who will present the results of this new study in 2023, which recruited 415 patients with recurrent ovarian cancer. All of them first received preoperative platinum-based chemotherapy. Up to 6 courses of chemotherapy will be administered. After three courses of chemotherapy, the patients will be pre-selected, if the cancerous lesions are deemed operable by the surgeon. Five to eight weeks after chemotherapy ends, patients will have surgery to remove the cancerous lesions. During this procedure, if the surgery is complete, the patients will be randomly divided into 2 treatment groups: one benefiting from HIPEC and the other not. The results with an average follow-up of more than 6 years were presented at the ASCO 2023 congress. Result: the overall survival of the treated group was 54.3 months compared to 45.8 months for the untreated group. A statistically significant result with nearly 9 months gained.

This technique could therefore reach more patients with the same initial diagnosis. Still, it requires calling on expert centers with hyper-specialized teams.

These two studies, as well as the one on the addition of two targeted therapies to post-surgery chemotherapy, testify to the significant dynamism of research in the face of this formidable cancer. These trials also testify to the importance of knowing the mutation status of tumors – their characteristics – (BRCA overexpression, genomic instability, alpha folate receptor, PDL-1, etc.) in order to be able to choose the most suitable treatment for each patient.