Ovarian cancer research at ESMO Congress explores chemotherapy-free treatment options
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MADRID — This year’s ESMO Congress included research updates that provide valuable data on chemotherapy-free treatment options being explored in recurrent ovarian cancer.
Kosei Hasegawa, MD, PhD, associate professor at Saitama Medical University International Medical Center, said during a discussion on data presented from two trials — phase 3 results from NRG-GY004 and phase 2 results from NRG-GY023 — that potential benefits of chemotherapy-free treatments include “reduced toxicity, and [improved] quality of life, improved adherence to treatment plans, individualized treatments, expanding treatment options, overcoming chemo resistance issues, enhanced survivorship and long-term outcomes.”
He added that “on the other hand, potential disadvantages would be limited efficacy as monotherapy treatment, and probably cost would be an issue.”
Phase 3 NRG-GY004 results
Joyce F. Liu, MD, MPH, associate chief and director of clinical research in the division of gynecologic oncology at the Dana-Farber Cancer Institute, presented phase 3 data on NRG-GY004.
“As a background, the combination of cediranib, which is a small-molecule [tyrosine kinase inhibitor (TKI)] with VEG-F activity, and olaparib was previously reported in a phase 2 study to have clinical activity in recurrent platinum-sensitive ovarian cancer,” Liu said. “We therefore conducted NRG-GY004, which is a randomized phase 3 trial comparing combination cediramib (AstraZeneca) and olaparib (Lynparza; AstraZeneca, Merck) or olaparib monotherapy to platinum-based chemotherapy in this setting.”
Researchers randomized patients 1:1:1 to each treatment arm.
A total of 565 eligible participants were enrolled in the study. Among the patients who initiated treatment, 167 received chemotherapy, 187 received olaparib monotherapy, and 183 received cediranib plus olaparib.
There were 51 withdrawals in the chemotherapy group, 15 withdrawals in the olaparib group, and 20 withdrawals in the cediranib plus olaparib group.
“In conclusion, neither olaparib nor the combination of cediranib and olaparib improved overall survival as a treatment for relapsed platinum-sensitive ovarian cancer,” Liu said during the presentation.
Liu noted that the hazard ratio for OS in both the olarapib monotherapy group and the cediranib plus olaparib group exceeded 1 and had wide 95% CI intervals.
She also explained that the interpretation of the study results were complicated by the high number of participants who withdrew from the study early.
Phase 2 NRG-GY023 results
Jung-Min Lee, MD, a Lasker Clinical Research Scholar in the Women's Malignancies Branch of the NCI Center for Cancer Research, presented results from the phase 2, open-label, randomized trial.
The trial included patients with high-grade serous/endometriod or clear cell platinum-resistant ovarian cancer who had received two to five prior systemic therapies, including prior use of bevacizumab.
Patients were randomly required 1:2:2:2 to receive standard of care with weekly paclitaxel, topotecan or liposomal doxorubicin, durvalumab (Imfinzi, AstraZeneca), olaparib and cediranib (DOC), durvalumab and cediranib (DC), and olaparib and cediranib (OC).
At the time of the data cutoff for the interim analysis on Oct. 31, 2022, 120 patients were enrolled in the study. The median age of these patients was 65 years, and 10% had either a germline or somatic BRCA mutation. At the data cutoff, the median follow-up period was 4.3 months.
Among the participants, the median PFS was 4.2 (95% CI, 1.9-5) with standard of care, 2.6 (95% CI, 2-4.2) with DOC, 2.3 (95% CI, 2-4.6) with DC and 2.3 (95% CI, 2.1-3.9) with OC.
Researchers found that, compared with standard of care, the hazard ratio estimates were 1.01 (95% CI, 0.44-2.31) for DOC, 1.21 (95% CI, 0.52-2.84) for DC and 1.34 (95% CI, 0.58-3.08) for OC.
“In summary, none of the experimental arms improved the progression free survival in heavily pretreated bevacizumab pre-exposed platinum-resistant ovarian cancer patients,” Lee said.
Looking forward
During the discussion, Hasegawa noted that “unfortunately the results of both trials were not positive, though I think both made substantial progress for therapy with chemo-free combination treatment in recurrent ovarian cancer.”
He added that while these and other studies in chemotherapy-free treatment regimens have not shown superiority to chemotherapy, he believes that there is a future for these regimens in recurrent ovarian cancer.
“There are many targets for each ovarian cancer subtype and the corresponding molecule targeted drugs in development,” Hasegawa said. “We expect that any combination of these will lead to the development of chemo-free regimen in the near future.”
References:
- Hasegawa K. Invited Discussant LBA45 and 746MO. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
- Lee JM, et al. Abstract 746MO. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
- Liu JF, et al. Abstract LBA45. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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Hasegawa K. Invited Discussant LBA45 and 746MO. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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