Despite the challenges of an ongoing COVID-19 pandemic, researchers in 2021 delivered practice-changing studies in gynecologic oncology. In this cancer Update, we highlight 4 studies that shed light on the surgical and systemic therapies that may improve outcomes for patients with cancers of the ovary, endometrium, and cervix. We review DESKTOP III, a trial that investigated the role of cytoreductive surgery in patients with recurrent ovarian cancer, and SENTOR, a study that evaluated the performance of sentinel lymph node biopsy in patients with high-grade endometrial cancers. Additionally, we examine 2 studies of systemic therapy that reveal the growing role of targeted therapies and immuno-oncology in the treatment of gynecologic malignancies.
A new era for patients with BRCA mutation–associated ovarian cancer
Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22:1721-1731.
Ovarian cancer remains the most lethal gynecologic malignancy due to the frequency of advanced-stage diagnosis and frequent relapse after primary therapy. But for ovarian cancer patients with inherited mutations of the BRCA1 or BRCA2 genes, poly(ADP-ribose) polymerase (PARP) inhibitors, a class of oral anticancer medicines that target DNA repair, have ushered in a new era in which the possibility of long-term remission, and even cure, is more likely than at any other time.
Olaparib trial details
The SOLO1 study was a double-blind, placebo-controlled, phase 3 trial that investigated the role of PARP inhibitor maintenance therapy with olaparib in patients with pathologic BRCA1 or BRCA2 mutations who responded to platinum-based chemotherapy administered for a newly diagnosed, advanced-stage ovarian cancer.1 The study enrolled 391 patients, with 260 randomly assigned to receive olaparib for 24 months and 131 patients randomly assigned to receive placebo tablets. Most patients in the study had a mutation in the BRCA1 gene (72%), 27% had a BRCA2 mutation, and 1% had mutations in both genes.
The primary analysis of SOLO1 was published in 2018 and was based on a median follow-up of 3.4 years.1 That study showed that olaparib maintenance therapy resulted in a large progression-free survival benefit and led to its approval by the US Food and Drug Administration (FDA) as a maintenance therapy for patients with BRCA-mutated advanced ovarian cancer who responded to first-line platinum-based chemotherapy.
In 2021, Banerjee and colleagues updated the progression-free survival results for the SOLO1 trial after 5 years of follow-up.2 In this study, the patients randomly assigned to olaparib maintenance therapy had a persistent and statistically significant progression-free survival benefit, with the median progression-free survival reaching 56 months among the olaparib group compared with 13.8 months in the placebo group (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.25–0.43).2 Olaparib maintenance therapy resulted in more clinically significant adverse events, including anemia and neutropenia. Serious adverse events occurred in 55 (21%) of the olaparib-treated patients and 17 (13%) of the placebo-treated patients, but no treatment-related adverse events were fatal.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
The updated progression-free survival data from the SOLO1 study provides important and promising evidence that frontline PARP inhibitor maintenance therapy may affect long-term remission in an unprecedented proportion of patients with BRCA-related ovarian cancer. Significant, sustained benefit was seen well beyond the end of treatment, and median progression-free survival was an astonishing 3.5 years longer in the olaparib treatment group than among patients who received placebo therapy.
The updated progression-free survival data from the SOLO1 study provides important and promising evidence that frontline PARP inhibitor maintenance therapy may affect long-term remission in an unprecedented proportion of patients with BRCA-related ovarian cancer. Significant, sustained benefit was seen well beyond the end of treatment, and median progression-free survival was an astonishing 3.5 years longer in the olaparib treatment group than among patients who received placebo therapy.
Continue to: Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients...