Camille C. Gunderson, MD, assistant professor of gynecologic oncology, Stephenson Cancer Center, discusses the use of PARP inhibitors in all-comers with ovarian cancer.

In December 2018, olaparib (Lynparza) received regulatory approval as frontline maintenance therapy in patients with advanced ovarian cancer who harbor germline or somatic 

 mutations. The decision is based on data from the phase III SOLO-1 trial, which showed a significant benefit in progression-free survival and time to first and second subsequent therapy or death with the agent versus placebo. Though data from the phase III PAOLA-1, PRIMA, and VELIA trials all showed a benefit with maintenance PARP inhibition in this setting, none of the other FDA-approved PARP inhibitors have received regulatory approval as frontline maintenance therapy, says Gunderson.

The benefit of PARP inhibition was observed in all-comers in these 3 trials, irrespective of homologous recombination deficiency (HRD) status or 

status, begging the question of whether bevacizumab (Avastin) or PARP maintenance should be used in patients with HRD defects or somatic 

mutations. The benefit of frontline PARP maintenance is clear in patients with germline 

mutations, says Gunderson. However, the benefit in all-comers will make patient selection more challenging, she concludes.

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Dr. Gunderson on the Use of PARP Inhibitors in All-Comers With Ovarian Cancer

Camille C. Gunderson, MD, assistant professor of gynecologic oncology, Stephenson Cancer Center, discusses the phase III open-label GOG-252 trial (NCT01167712) in advanced ovarian cancer.

No progression-free survival (PFS) or overall survival (OS) benefit was reported with the use of intraperitoneal (IP) chemotherapy compared with intravenous (IV) chemotherapy, both combined with bevacizumab (Avastin), in patients with newly diagnosed advanced ovarian cancer.

After a median follow-up of 84.4 months, PFS in the IV carboplatin group was 24.9 months compared with 27.4 moths in the IP carboplatin group (HR, 0.925; 95% CI, 0.802-1.07). A third arm of IP cisplatin was tested and yielded a PFS of 26.2 (HR, 0.977; 95% CI, 0.847-1.13).

Median OS was 75.5 months, 78.9 months, and 72.9 months, in the IV carboplatin, IP carboplatin, and IP cisplatin arms, respectively. More frequent grade ≥3 adverse events including infections, nausea, vomiting, and hypertension were seen with IP chemotherapy compared with IV chemotherapy (

Patients with no gross residual disease and a somatic 

 mutation, may benefit the most from IP chemotherapy, says Gunderson. However, with similar PFS and OS, the lower incidence of toxicity suggests that IV chemotherapy may be preferable to IP chemotherapy.

Camille C. Gunderson, MD, discusses the phase III open-label GOG-252 trial in advanced ovarian cancer.
 

Camille C. Gunderson, MD

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Dr. Gunderson on the Use of PARP Inhibitors in All-Comers With Ovarian Cancer

Dr. Gunderson on the GOG-252 Trial in Advanced Ovarian Cancer