New advancements in the treatment of ovarian cancer have transformed the lives of many women. The introduction of targeted therapies such as anti-angiogenic agent bevacizumab (Avastin) and three poly-ADP ribose polymerase (PARP) inhibitors olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca) into a chemotherapy-dependent treatment paradigm enabled an unprecedented improvement in the survival outcomes. Regardless, high recurrence rate and treatment resistance are persistent unmet needs in ovarian cancer. The American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program, held 29 May – 2 June, reported results from clinical trials and highlighted several key developments in the treatment of ovarian cancer, which collectively highlight the value of new therapies in different patient subgroups and offer guidance to the treatment of recurrent ovarian cancer.
One of the highly anticipated presentations in ASCO 2020 was the data readout from DESKTOP III/ENGOT-ov20 trial (abstract #6000), which demonstrated a clear survival benefit from secondary cytoreductive surgery in recurrent ovarian cancer. While secondary resection increased OS by 8 months and reduced the risk of death by 25%, patients with complete secondary resection showed extended OS by 15 months when compared to patients who did not receive surgery. The study also underlines a 76% success rate in achieving complete resection by using Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) scoring system that was based on good performance score and lack of residual disease following the primary surgery.
While the DESKTOP III study results could be practice-changing in recurrent ovarian cancer, AstraZeneca presented previously announced final results from the SOLO-2 trial for their PARP inhibitor Lynparza in platinum-sensitive ovarian cancer. According to the long-term data from this study (abstract #6002), maintenance therapy with Lynparza provided nearly 13 months OS benefit and 20 months delay of subsequent therapy over placebo in patients who have responded to platinum chemotherapy. A 42% median 5-year survival rate in the Lynparza arm, compared to 33% in the placebo arm, is also remarkable and it shows how drastically the outcomes from treatment in ovarian cancer has improved.
In the Phase Ib/II FORWARD II study (abstract #6004), ImmunoGen’s folate receptor alpha (FRα) targeting antibody-drug conjugate, mirvetuximab soravtansine, in combination with Avastin, generated a 47% overall response rate (ORR) in all of the study cohorts, with a reduction in tumour burden in 92% of the patients. Responses were deeper and more durable in FRα+ patients, and more importantly, in the platinum-resistant cohort with high FRα expression, the combination reached 60% ORR. These results are encouraging, especially considering that in Phase III FORWARD I study the confirmed ORR for mirvetuximab soravtansine monotherapy was only 24% in FRα+ platinum-resistant patients (NCT02631876). Whether or not the higher activity observed in the FORWARD II trial would ultimately translate to a survival benefit is still uncertain. However, remarks from key opinion leaders, despite the negative results from the FORWARD I trial, underscore the strengths of the drug’s biomarker-driven activity in platinum-resistant patients, in which the incidence of high expression of FRα is more than 70%.
It is important that physicians and drug developers continue their efforts to develop better treatment guidelines and bring new therapies for patients with recurrent and treatment-resistant ovarian cancer to market. As the three selected presentations from the ASCO 2020 Virtual Scientific Program reiterate, clinical trials are taking place, new standards of treatment are still being formed, and novel therapies continue to offer hope for longer lives for recurrent ovarian cancer patients.