Current Treatment May Be Superior to Recentin In Ovarian Cancer

Recentin-containing regimens showed promise in ovarian cancer but ultimately proved less effective than current standard-of-care treatments.

Among patients with platinum-resistant or platinum-refractory epithelial ovarian cancer, treatment with Recentin (cediranib)-containing regimens demonstrated clinical benefits in progression-free survival, however, it was not superior when compared with the currently available standard-of-care chemotherapy, as per a study.

“Although [Recentin plus Lynparza] did not meet the primary [goal] of increasing [progression-free survival] or [overall survival] compared with nonplatinum single-agent [standard-of-care chemotherapy], combination [Recentin plus Lynparza] demonstrated some evidence of durable clinical [benefits] in patients with [platinum-resistant or platinum-refractory epithelial ovarian cancer] with no new safety signals,” researchers wrote in the study published in Journal of Clinical Oncology.

After a median follow-up of 42.2 months, the median progression-free survival rate was 3.4, 5.2 and four months in the standard-of-care, Recentin plus Lynparza (olaparib) and Recentin-alone groups, respectively. The median overall survival was 13.6, 12.8 and 10.5 months for standard-of-care, the combination and Recentin alone, respectively. Among 443 patients with measurable disease, the objective response rate was 8.6%, 24.7% and 13.1% for standard-of-care, the combination and Recentin alone, respectively.

Nonhematologic side effects in the Recentin plus Lynparza compared with Recentin alone included diarrhea (74.9% and 76.5%, respectively, with 8% and 12.3% being severe or life-threatening), fatigue (76.1% and 64.2% respectively; 17.2% and 11.1% severe or life-threatening) and hypertension (65% and 75.3%, respectively; 28.2% and 42% severe or life-threatening).

“The [side effect] pattern was as expected for [Recentin plus Lynparza] such as diarrhea, fatigue, nausea and hypertension,” study authors mention.

Of note, patient-reported outcomes demonstrated no statistically different disease-related physical symptoms for Recentin plus Lynparza; however, Recentin alone showed worse scores during the first year after starting treatment.

Patients on Recentin alone reported 2.2 points worse than those on standard of care at 12 weeks and 2.7 points worse than those on Recentin plus Lynparza at 48 weeks. According to the study, “larger scores suggest a better or preferable state of health.”

Three patients died, possibly due to treatment: one from gastric obstruction after her first cycle of Recentin plus Lynparza, one from intestinal obstruction on chemotherapy and one from leukemia considered definitely related to chemotherapy. About 18% and 27% of patients on the Recentin plus Lynparza and Recentin alone groups, respectively, discontinued treatment due to side effects. Additionally, 65% to 70% of patients in Recentin-containing groups required dose modifications within the first six cycles of therapy.

Among patients who experienced side effects, 18% withdrew treatment from the Recentin plus Lynparza group. In addition, 65% of patients underwent a dose modification because of side effects within the first six cycles. There were no new safety concerns that emerged during the trial.

Out of a total of 510 patients, most (96.7%) had high-grade serous carcinoma. Among those tested, 7.8% (33 of 422) had germline BRCA1 or BRCA2 mutations. About one-third (31.6%) of patients had primary platinum-refractory disease and 19.2% had received previous adjuvant (postsurgical) Avastin (bevacizumab).

Notably, in the Phase 3 AURELIA trial, Avastin had emerged as a mainstay of therapy for with platinum-resistant or platinum-refractory epithelial ovarian cancer before the current trial was conducted. While not improving overall survival, the Phase 3 study established it as standard-of-care with chemotherapy.

“This observed activity highlights the need for further investigation of biomarkers to identify those most likely to benefit and minimize toxicity in those with cancers unlikely to respond,” study authors concluded.

Reference:

“Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005” by Dr. Jung-Min Lee, et al., Journal of Clinical Oncology.

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