David O'Malley, MD, professor, Department of Obstetrics and Gynecology, The Ohio State University Comprehensive Cancer Center, discussed the safety and efficacy results of the FORWARD II phase Ib study in patients with ovarian cancer.

The trial examined mirvetuximab soravtansine (IMGN853) in combination with bevacizumab (Avastin) in patients with platinum-resistant ovarian cancer. The phase Ib study is part of a larger phase Ia/b trial looking at 3 separate combinations—carboplatin and mirvetuximab soravtansine, bevacizumab and mirvetuximab soravtansine, and pegylated liposomal doxorubicin and mirvetuximab soravtansine. The overall population of 54 patients experienced about a 40% objective response rate with about a 9-month progression-free survival, says O’Malley.

The study encompassed escalation and expansion cohorts, so researchers divided patients into subsets in an attempt to mirror protocols like FORWARD I. The phase I study used the single-agent protocol requiring 1 to 3 prior therapies in patients with medium- and high-folate receptor expression. Another subgroup was extracted to be consistent with the population in the AURELIA trial. Those patients likewise received 1 to 2 prior lines of therapy and were divided by medium and high folate-receptor expression.

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David O’Malley, MD, professor, Department of Obstetrics and Gynecology, The Ohio State University Comprehensive Cancer Center, discusses the safety and efficacy results of the FORWARD II phase Ib study in patients with ovarian cancer.

Dr. O'Malley on the FORWARD II Phase Ib Study in Ovarian Cancer

David O'Malley, MD, gynecologic oncologist and an assistant professor in the Department of Obstetrics and Gynecology at The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center, discusses the FDA approval of rucaparib (Rubraca) for use as a maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

David O'Malley, MD, gynecologic oncologist and an assistant professor in the Department of Obstetrics and Gynecology at The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center, discusses the FDA approval of rucaparib (Rubraca)

Dr. O'Malley on FDA Approval of Maintenance Rucaparib in Ovarian Cancer

David O'Malley, MD, a professor in the Department of Obstetrics and Gynecology at The Ohio State University Comprehensive Cancer Center, discusses combinations with PARP inhibitors in ovarian cancer.

There are multiple phase III trials in the frontline, recurrent, and platinum-sensitive settings investigating combinations of PARP inhibitors with other agents in patients with ovarian cancer. It is difficult to combine PARP inhibitors with classic cytotoxic agents like platinum-based chemotherapy, says O’Malley.

In combination, PARP inhibitors seem to be best tolerated with biologic therapies, O’Malley says. A phase III trial of olaparib (Lynparza) and the angiogenesis inhibitor cediranib has been completed, but results have not been released. In updated findings from a phase II trial of olaparib and cediranib maleate, the combination showed superior progression-free survival versus olaparib alone in patients with 

-negative recurrent platinum-sensitive ovarian cancer.

O’Malley says that any patient with ovarian cancer who is eligible for a clinical trial should be enrolled on one.

Dr. O'Malley Discusses PARP Combinations in Ovarian Cancer

David O'Malley, MD, a professor in the Department of Obstetrics and Gynecology at The Ohio State University Comprehensive Cancer Center, discusses the tolerability of PARP inhibitors for patients with ovarian cancer.

The toxicity is somewhat of a challenge, explains O’Malley. Patients find that when taking agents daily, oral agents are particularly convenient. There are adverse events such as fatigue, gastrointestinal side effects, and hematologic events, which can limit the quality of life in patients. However, due to patient-reported outcomes, physicians can keep the disease from coming back in the maintenance phase in platinum-sensitive disease, and those patients can do better.

When comparing treatment from placebo with PARP inhibitors, there is not much difference, says O’Malley. There are side effects that need to be balanced, and it is important to look at patient-reported outcomes moving forward to ascertain the best place to use these drugs, he adds. Overall, PARP inhibitors are well tolerated, but there are some side effects that can impact a patient's quality of life, specifically, fatigue and gastrointestinal side effects.

Dr. O'Malley on the Tolerability of PARP Inhibitors in Ovarian Cancer

David O'Malley, MD, a professor in the Department of Obstetrics and Gynecology at The Ohio State University Comprehensive Cancer Center, discusses the current role for PARP inhibitors for patients with ovarian cancer.

PARP inhibitors have a role in a couple of different patient populations, explains O’Malley. One of those populations is 

 mutations, either germline or somatic. Olaparib (Lynparza) has indications in patients with a germline mutation who have had 3 or more prior lines of therapy, while rucaparib (Rubraca) is indicated for both somatic and germline tumors with more than 2 lines of prior therapy.

There are now 2 drugs that are approved in the platinum-sensitive maintenance setting. Those are olaparib and niraparib (Zejula). According to O’Malley, rucaparib has been submitted to the FDA but it is not known if it will receive approval.

In this population of patients, many of the trials are concentrated on 

 mutations as well as homologous recombination deficiency status. Both current drugs are approved in all-comers no matter their somatic or germline status.

David O'Malley, MD

Articles

Dr. O'Malley on the FORWARD II Phase Ib Study in Ovarian Cancer

Dr. O'Malley on FDA Approval of Maintenance Rucaparib in Ovarian Cancer

Dr. O'Malley Discusses PARP Combinations in Ovarian Cancer

Dr. O'Malley on the Tolerability of PARP Inhibitors in Ovarian Cancer

Dr. O'Malley Discusses the Current Role of PARP Inhibitors in Ovarian Cancer