Dose-Dense Chemo Regimen No Better Than Standard of Care for Epithelial Ovarian Cancer

Getting a weekly high dose of chemotherapy for epithelial ovarian cancer did not improve survival outcomes over standard of care for patients with epithelial ovarian cancer, but it was a safe and effective treatment regimen, according to research recently presented at the ESMO Virtual Congress 2020.

“There’s a strong rationale for the evaluation of weekly-dose paclitaxel after settling into the first line of treatment,” Dr. Andrew Clamp, senior lecturer and honorary consultant in medical oncology at the Christie NHS Foundation Trust, said while presenting findings from the ICON8 study.

Study Outcomes For Patients With Epithelial Ovarian Cancer

There were more than 1,500 eligible patients with epithelial ovarian cancer enrolled in the study. They were randomly assigned to one of three treatment arms:

• Arm 1: standard chemotherapy consisting of carboplatin AUC5/6 plus paclitaxel 175 mg/m2, both given every three weeks(522 patients)
• Arm 2: carboplatin AUC5/6 every three weeks plus paclitaxel 80mg/m2 once a week (523 patients)
• Arm 3: carboplatin AUC2 plus paclitaxel 80 mg/m2, both given once a week (521 patients)

Patient characteristics were well balanced among the arms at the start of treatment. The average age of study participants was 62, and 72% had serous disease. Regarding disease stage, 10.5% had stage 1c-2a cancer, 18% had stage 2a-3b and 71% had stage 3c-4. Half (50%) of patients planned delayed primary surgery, while slightly less (48%) underwent immediate primary surgery. Two percent of patients had inoperable disease.

The average overall survival (OS), meaning the total percentage of patients alive on Oct. 1, 2019, was 47.4, 54.1 and 53.4 months in arms 1, 2 and 3, respectively. There were 319 deaths in arm 1 (61%), 300 deaths in arm 2 (57%) and 304 deaths in arm 3 (58%). The difference in survival was not statistically significant between the dose-dense arm and the other two.

Managing Side Effects

Average time to disease progression was 25, 25.5 and 25.9 months in arms 1, 2 and 3, respectively, again showing no statistically significant difference between the arms.

However, the high-dose regimen did have an acceptable side-effect profile, Clamp explained. The side effects associated with the regimens have not changed since researchers analyzed them in 2017.

“The two weekly treatment arms were associated with an increased incidence of any grade 3 or 4 events during treatment,” predominantly driven by neutropenia, a blood count deficiency, Clamp said. “Reassuringly, incidence of febrile neutropenia was low in all three treatment arms, and we did not see any increase of grade 2 or more sensory neuropathy (tingling or numbness in the extremities) in the two weekly dose-dense paclitaxel-containing regimens.”

While there was no major difference in patient characteristics between the treatment groups, Clamp explained that further research will look into more distinct subgroups of patients with ovarian cancer to see if the dose-dense regimen has different survival rates.

“Other further hypothesis-generating analyses are underway in our delayed primary surgery cohort to determine if there is a subgroup of patients who may benefit with the more dense approach,” Clamp said.