Dr Corr on the Rationale for Investigating Rucaparib Maintenance in Endometrial Cancer

Bradley R. Corr, MD, associate professor, LeBert Suess Family Endowed Professor in Ovarian Cancer Research, gynecologic oncology team, the University of Colorado Anschutz Medical Campus, discusses the rationale for and findings from a phase 2 study (NCT03617679) evaluating the use of maintenance therapy with rucaparib (Rubraca) vs placebo in patients with metastatic and recurrent endometrial cancer.

The use of PARP inhibitors has expanded across several tumor types, including breast, ovarian, and prostate cancers. These agents are particularly beneficial for patients with 

 mutations or homologous recombination–deficient disease, Corr says. However, preclinical data show that differential DNA activity may be present in endometrial cancer, which is typically a mutation-driven disease, Corr explains. Based on these preclinical findings, Corr and colleagues launched a phase 2 trial of rucaparib vs placebo maintenance therapy in patients with metastatic or recurrent endometrial cancer who had received 1 to 2 prior lines of cytotoxic chemotherapy.

In the intent-to-treat population, this study showed a median progression-free survival (PFS) of 28.1 months (95% CI, 12.8-not yet reached [NR]) in the rucaparib arm (n = 39) vs 8.7 months (95% CI, 5.4-16.7) in the placebo arm (n = 40), translating to a 19.4 month PFS improvement with the PARP inhibitor vs placebo (HR, 0.45; 95% CI, 0.26-0.80; 

 = .005), Corr notes. In a subgroup analysis ofpatients with stage III or IV disease, the median PFS was 21.1 months (95% CI, 6.8-NR) with rucaparib (n = 28) vs 9.2 months (95% CI, 5.4-18.4) with placebo (n = 30; HR, 0.52; 95% CI, 0.27-1.01; 

 = .049). Among patients with recurrent disease, the median PFS was 28.5 months (95% CI, 13.5-NR) with rucaparib (n = 11) vs 7.6 months (95% CI, 2.3-NR) with placebo (n = 10; HR, 0.33; 95% CI, 0.11-1.03; 

 = .046). These findings hold significant implications for patients with metastatic and recurrent endometrial cancer, Corr concludes.

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Bradley R. Corr, MD, discusses a phase 2 study evaluating rucaparib maintenance therapy in patients with metastatic and recurrent endometrial cancer.

Bradley R. Corr, MD, assistant professor of gynecologic oncology, Division of Gynecologic Oncology, University of Colorado Anschutz Medical Campus, UCHealth, discusses the utilization of molecular profiling in endometrial cancer.

Molecular profiling has quickly evolved to be the standard of care for patients with endometrial cancer, Corr says. This is because molecular profiling continues to dictate thoseappropriate therapies for patients as the field advances significantly, Corr explains. Moreover, the National Comprehensive Cancer Network guidelines recommend molecular testing for patients with standard, mismatch repair deficient, 

As these recommendations develop, molecular markers are being identified, as areefficacious therapies targeted toward these molecular markers, Corr continues. This is helping to not only dictate which therapies are used, but also which tumors don't require therapy, Corr says. As such, molecular testing is informing clinical trial development, as well as informing treatment selecting for patients with endometrial cancer, Corr concludes.

Bradley R. Corr, MD, discusses the utilization of molecular profiling in endometrial cancer. 


Dr. Corr on the Utilization of Molecular Profiling in Endometrial Cancer 

Bradley Corr, MD, assistant professor of Obstetrics/Gynecology, Gynecologic Oncology, University of Colorado School of Medicine, discusses the rationale to evaluate WNT pathway inhibition in gynecologic cancers. 

Targeting the WNT pathway has been an area of ongoing research in breast, colon, and gynecologic cancers for many years, explains Corr. Now, pharmaceutical companies have taken an interest in developing WNT pathway–targeted agents, which has led to a growing body of knowledge in gynecologic cancers, explains Corr.

Specifically, copy number–low endometrial cancers that harbor 

 mutations appear to have direct clinical significance with WNT inhibition, explains Corr.* Conversely, in ovarian cancer, mutational status does not seem to inform whether patients would be candidates for WNT targeted therapy, Corr says. However, crosstalk within the WNT pathway does exist in ovarian cancer, so it remains an area of active research. 

Notably, targeting the WNT pathway with single-agent or combination regimens may provide an option for patients who develop resistance to PARP inhibitors in ovarian and endometrial cancers, concludes Corr.

Bradley Corr, MD, discusses the rationale to evaluate WNT pathway inhibition in gynecologic cancers.  


Bradley Corr, MD

Articles

Dr Corr on the Rationale for Investigating Rucaparib Maintenance in Endometrial Cancer

Dr. Corr on the Utilization of Molecular Profiling in Endometrial Cancer

Dr. Corr on the Rationale to Evaluate WNT Inhibition in Gynecologic Cancers