Editor's note: The 2023 ESMO released several research advances in the field of gynecologic oncology, and Oncology Frontier invited Domenica Lorusso of the Catholic University of the Sacred Heart in Milan, Italy, to comment on the latest results of the DUO-E and KEYNOTE-A18 trials.
Oncology Frontier: 2023 ESMO released the data of olaparib vs placebo as maintenance therapy after platinum-based chemotherapy in advanced/metastatic endometrial cancer patients. Would you please comment on the result of phase IIb UTOLA trial?
Dr Lorusso: During ESMO 2023, we have presented the results of DUO-E, suggesting for the first time in endometrial cancer, a benefit from the combination of olaparib plus durvalumab in the setting of advanced or recurrent endometrial cancer. The trial was a three-arm comparator trial - chemotherapy (carboplatin/paclitaxel), chemotherapy plus immunotherapy (durvalumab), and chemotherapy plus immunotherapy plus PARP inhibitor. The trial demonstrated that in the dMMR (mismatch repair-deficient) population, chemotherapy plus immunotherapy is the new standard-of-care. In the pMMR (mismatch repair proficient) population, the combination of chemotherapy plus immunotherapy plus PARP inhibitor reduced the risk of progression by 55% with respect to chemotherapy. I think this new four-drug combination should be considered a standard option for pMMR patients with advanced or recurrent endometrial cancer.
Oncology Frontier: Please talk about the clinical value of HRD testing in ovarian cancer.
Dr Lorusso: It is
absolutely important now to test the patient with HRD. We already know the
value of testing in ovarian cancer, because it is prognostic and predictive.
What is happening now is that in endometrial cancer as well, we know that there
is a group of patients (up to 35% of all patients) with some differences
between serous and non-serous endometrial cancer that present HRD or HRR
mutations. The next challenge of clinical research will be how to identify
these patients, and if HRD/HRR tests are the driver of the response to PARP
inhibitors to better select who are the pMMR patients to respond to PARP
inhibitors.
Oncology Frontier: Based on the results of the KEYNOTE-A18 trial (LBA38), whether pembrolizumab plus chemoradiotherapy is a promising regimen for high-risk locally advanced cervical cancer?
Dr Lorusso: We
presented here at ESMO, the research from the KEYNOTE-A18 trial, evaluating for
the first time, the role of pembrolizumab in combination with chemoradiation in
locally advanced high-risk cervical cancer. The trial reported a significant and
clinically relevant increase in progression-free survival with a hazard ratio
of 0.7, suggesting a 30% reduction in the risk of progression and a trend
towards an increase in overall survival, even though the overall survival data
are not yet mature. I think that for the first time in the context of high and
good quality radiotherapy, we are very confident of the added value of
pembrolizumab. That is why I think this is the new standard-of-care in locally
advanced high-risk cervical cancer.