In 2021, the COVID-19 pandemic continued to impact the practice of medicine and dissemination of treatment advances presented in scientific forums. Medical societies, such as the American Society of Clinical Oncology and the Society of Gynecologic Oncology, have adopted hybrid formats, including virtual meetings that delivered cutting-edge research in the advancement of oncology care. In addition, several treatment advances continue to be published in peer-reviewed journals. We are publishing the Year in Review series to disseminate key information on treatment advances to clinicians in a timely and effective manner.
This edition of Year in Review is focused on ovarian cancer, which is associated with high mortality despite significant treatment improvements. Several approved and novel classes of agents continue to be investigated in ovarian cancer to produce better patient outcomes. Here is a quick review of some of the topics discussed in this issue, with a focus on recent advances and potentially practice-changing developments in ovarian cancer.
Treatment options for the management of relapsed ovarian cancer primarily include antiangiogenics, such as bevacizumab, and poly (ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib, niraparib, and rucaparib). Treatment selection is dictated by disease- and patient-related factors, with tumor biology having a key role, particularly genetic alterations resulting in homologous recombination deficiencies (HRDs), such as germline or somatic BRCA1/2 mutations.
Overall survival analysis of the open-label, nonrandomized, phase 2 LIGHT clinical trial demonstrated that olaparib therapy in patients with platinum-sensitive relapsed ovarian cancer achieved an overall survival benefit across patient cohorts regardless of BRCA mutation and HRD status, with the greatest benefit observed in cohorts of patients with BRCA mutation–positive disease. Subgroup analysis of the phase 3 ARIEL4 study suggests that heavily pretreated patients with advanced relapsed ovarian carcinoma harboring a BRCA1/2 mutation derive progression-free survival (PFS) benefit with rucaparib therapy across all platinum sensitivity subgroups. These agents are further being investigated in the first-line setting and as maintenance therapy, which has implications for next lines of therapy since previous exposure to these agents influences options for recurrent disease.
The role of PARP inhibitors as maintenance therapy following response to platinum-based chemotherapy is also being investigated. In patients with newly diagnosed advanced ovarian cancers with BRCA1/2 mutations, the 5-year follow-up results of the SOLO1 trial indicate that 2 years of maintenance olaparib provided sustained PFS benefit, with no new safety signals. Subgroup analyses of the phase 3 PAOLA-1 trial demonstrated sustained PFS benefit with the addition of maintenance olaparib to bevacizumab compared with placebo in patients with newly diagnosed, HRD-positive, advanced, high-grade ovarian cancer, irrespective of the International Federation of Gynecology and Obstetrics stage and residual disease after upfront surgery. The final analysis of the NOVA trial supports the long-term safe use and PFS benefit beyond first progression of niraparib for maintenance treatment in patients with platinum-sensitive, recurrent ovarian cancer. Pooled analysis data from the PRIMA, NOVA, and NORA trials indicate that patients with BRCA mutation–positive ovarian cancer derived a significant PFS benefit from niraparib maintenance treatment, with emergence of no new safety signals. In addition, cost-effectiveness modeling analysis determined that olaparib was more cost-effective compared with niraparib as maintenance therapy for patients with recurrent platinum-sensitive ovarian cancer.
Antiangiogenic strategies are further being optimized, and novel agents, such as the VEGFR2 tyrosine kinase inhibitor apatinib (rivoceranib) and the multitargeted tyrosine kinase inhibitor anlotinib (AL3818), are being developed. Addressing the issue of optimal duration of bevacizumab treatment, data from a randomized phase 3 trial demonstrated that prolonged treatment with bevacizumab for up to 30 months does not provide survival benefit in patients with advanced ovarian cancer compared with bevacizumab treatment duration of 15 months. Results of the phase 2 APPROVE trial showed significant prolongation of PFS with the addition of apatinib to pegylated liposomal doxorubicin in patients with platinum-resistant or refractory recurrent ovarian cancer. Results of the ovarian cancer cohort of the multicohort phase 1b ACTION trial indicate that anlotinib plus the anti–PD-L1 monoclonal antibody TQB2450 showed encouraging antitumor activity and tolerable toxicity in patients with recurrent advanced ovarian cancer.
Ongoing clinical research efforts are also focused on identifying other pathways and strategies in the pathophysiology of ovarian cancer. These include the GAS6/AXL inhibitor batiraxcept (AVB-500), the WEE1 inhibitor adavosertib (AZD1775), the cyclin-dependent kinase 4/6 cell-cycle checkpoint inhibitor ribociclib, the antifolate receptor-α monoclonal antibody farletuzumab (MORAb-003), the antifolate receptor-α antibody–drug conjugate mirvetuximab soravtansine (IMGN853), and the immunotherapy with tumor-cell vaccine gemogenovatucel-T, which are all showing encouraging antitumor activities in patients with recurrent ovarian cancer. Results of the phase 2 EFFORT study support the efficacy of adavosertib with and without olaparib in patients with PARP inhibitor–resistant ovarian cancer. Moreover, phase 2b VITAL trial results suggest that immunotherapy with the autologous tumor-cell vaccine gemogenovatucel-T as frontline maintenance therapy in patients with stage III/IV ovarian cancer was well-tolerated and showed a clinical benefit in BRCA wild-type and HRD-proficient subgroups.
We are pleased to present the highlights of these topics and more!
Amina Ahmed, MD
Associate Professor, Division of Gynecologic Oncology
Department of Obstetrics and Gynecology
Rush University Medical Center
Chief Medical Officer-Rush University Cancer Center