Current and Future Options for Patients with Relapsed Ovarian Cancer. By Dr. Andrea Wahner-Hendrickson, Mayo Clinic Rochester, MN. HOTTEST TOPICS IN CLINICAL ROUTINE AND RESEARCH/ 12th International Charité Mayo Conference, 29. April 2023
Depending on patient preference, tumour biology, previous treatment, and time of recurrence, the treatment algorithms differentiate in the event of disease recurrence. It should always first be examined, in addition to the possibility of surgical intervention, whether a renewed platinum-containing regime is an option. Today, experts are increasingly moving away from the originally rather rigid temporal distinction between platinum resistance and platinum sensitivity - i.e. if the end of the last platinum therapy was less than or more than 6 months ago. If there is no intolerance or refraction (progression during or shortly after platinum-based chemotherapy), the repeated use of this highly effective substance class should be considered in each individual case.
In addition to carboplatin, or as monotherapy or combination therapy, other agents such as paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine or topotecan may be considered. If indicated, the administration of bevacizumab can be useful, and PARP inhibitors are prescribed if the BRAC mutation is present.
In the latter, the use of the original mono-treatment in the second and third line has shifted significantly to the first line and established itself there as a maintenance therapy, as the speaker also pointed out with regard to the latest ASCO guidelines.
Early relapses in particular are associated with a poor prognosis, also because treatment is often limited by systemic toxicity. The novel antibody-drug conjugates (ADCs) now fill precisely this gap. ADCs are drugs consisting of a monoclonal antibody directed against the tumour antigen, a cytostatic drug and a binding stucture element. After targeted binding, internalisation and cleavage of the so-called linker, the potent, cytotoxic substance is delivered directly into the tumour cell. In this way, systemic toxicity is strongly limited, which is expressed in a demonstrably good tolerability.
In particular, the convincing effectiveness of this method in large studies led to accelerated approval of mirvetuximab soravtansine in the USA in November 2022. This antibody-drug conjugate directed at the folate receptor alpha (FRα), with the combined cell toxin maytansinoid DM4, is indicated for FRα-positive cancers of the ovaries, fallopian tubes and peritoneum that are "platinum-resistant" in the classical sense. The combination or pre-therapy with bevacizumab proved to be favourable.
Since FRα is overexpressed in well over 80% of epithelial ovarian carcinoma, these patients could particularly benefit from treatment. In this context, Dr Wahner-Hendrickson was pleased with the results of the SORAYA study, in which 27% of the participants achieved partial tumour remission and a further 5% achieved complete tumour remission within the observation period of around 13 months.
The expert was able to give the all-clear regarding the described oculotoxic side effects: these were not permanent and could be easily controlled with eye drops.
Currently, the field of ADCs is expanding rapidly, with more than 20 potential formulations against various gynaecological malignancies in clinical trials. Meanwhile, overexpression of HER2/neu, Napi2b, mesothelin and the human trophoblast cell surface marker (Trop-2) have begun to be used as suitable targets of ADCs. Novel drug delivery platforms such as dolaflexin with a so-called scaffold linker are also being explored, as are the multiple possibilities of ADC combination therapies with immunological, cytostatic or anti-angiogenic agents.
While the first approved drug in this targeted therapy class is associated with excellent response rates and favourable safety profile in recurrent ovarian cancer, other promising ADCs are already on the horizon. They are expected to play a key role in the treatment of various gynaecological cancers in the future - especially in the previously difficult-to-target group of early recurrences.
Current and Future Options for Patients with Relapsed Ovarian Cancer. By Dr. Andrea Wahner-Hendrickson, Mayo Clinic Rochester, MN. HOTTEST TOPICS IN CLINICAL ROUTINE AND RESEARCH/ 12th International Charité Mayo Conference, 29. April 2023