New Agents Push the Envelope in Ovarian Cancer

Susana M. Campos, MD, MPH
Published: Sunday, Feb 10, 2019
Susana M. Campos, MD
Susana M. Campos, MD
Ovarian cancer is the fifth overall cause of cancer death in women, and it represents 5% of all cancers in women. Most women with ovarian cancer present with stage III or IV disease, which contributes to the high mortality rate. Although there have been numerous studies evaluating the role of different therapy schedules, cytotoxic agents, and routes of administration, the backbone of therapy remains a combination of a platinum and a taxane.

GOG-02181 and ICON72 evaluated the role of bevacizumab (Avastin) in the management of patients with newly diagnosed ovarian cancer. In GOG-0218, bevacizumab administered concurrently with chemotherapy and as maintenance treatment showed a statistically significant improvement in progression-free survival (PFS) compared with placebo (14.1 vs 10.3 months; HR, 0.717; P <.001). In ICON7, bevacizumab administered concurrently with chemotherapy and as maintenance treatment showed a statistically significant improvement in PFS compared with chemotherapy alone (19.9 vs 17.3 months; HR, 0.81; P = .004). The improvement was more pronounced for patients at high risk of progression (stage IV or FIGO [Fédération Internationale de Gynécologie et d’Obstétrique] stage III and greater than 1 cm of residual disease).

Despite these encouraging results, the addition of bevacizumab in the overall population did not result in improvement in overall survival (OS). Therefore, innovative combinations in the up-front setting of patients with ovarian cancer remain a high priority.

Parp Inhibitors

Recently, treatment in the landscape of ovarian cancer has changed. Notably, PARP inhibitors have been approved for the treatment of recurrent ovarian cancer. In 2014, olaparib (Lynparza) was approved for patients who carried a deleterious BRCA germline mutation and had received 3 or more prior lines of chemotherapy.3 Rucaparib (Rubraca)4 was approved as single-agent maintenance therapy for patients with germline or somatic BRCA mutations.

Recently, results from 4 pivotal trials, NOVA (niraparib; Zejula),5 SOLO-2 (olaparib),6 Study 19 (olaparib),7 and ARIEL III (rucaparib),8 demonstrated a PFS benefit in patients with platinum-sensitive recurrent disease who responded to therapy regardless of mutational status. In addition to rucaparib, niraparib and olaparib are approved as maintenance therapy.

In December 2018, the FDA approved olaparib for the frontline maintenance treatment of patients with germline or somatic BRCA mutations who are in complete or partial response to platinum-based chemotherapy.9

The approval was based on findings from the international, randomized, double-blind, phase III trial that evaluated the efficacy of maintenance olaparib in patients with newly diagnosed high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with BRCA1/2 mutations who had a complete or partial response after platinum-based chemotherapy. The primary endpoint was PFS.10

Table. 1 Ongoing Studies of PARP Inhibitors in Newly Diagnosed Ovarian Cancer

Table. 1 Ongoing Studies of PARP Inhibitors in Newly Diagnosed Ovarian Cancer

Table 2. Ongoing Studies of PARP Inhibitors Combined With Checkpoint Inhibitors in Newly Diagnosed Ovarian Cancer

Table 2. Ongoing Studies of PARP Inhibitors Combined With Checkpoint Inhibitors in Newly Diagnosed Ovarian Cancer After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo. The HR for disease progression or death was 0.30 (95% CI, 0.23-0.41; P <.001).9,10

Pending trials for newly diagnosed ovarian cancer that employ a PARP inhibitor include PRIMA, GOG 3005, and PAOLA-1 (Table 1).

Checkpoint Inhibitors

In the past several years, there has been tremendous benefit from the clinical implementation of checkpoint inhibitors, which have been approved for treatment of melanoma, Hodgkin lymphoma, and bladder, kidney, and lung cancers. However, the role of checkpoint inhibitors in ovarian cancer is undefined. Several questions remain: What effect can the immune system have on ovarian cancer? What factors contribute to ovarian cancer immunogenicity? What role does PD-L1 play in ovarian cancer?


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