Joining the ranks of key biomarkers such as folate receptor alpha (FRα) and HER2, PD-L1 expression will now be used to determine eligibility for treatment with immunotherapy in platinum-resistant, recurrent ovarian cancer, an avenue once thought questionable given the difficulty triggering robust immune responses with immune checkpoint inhibition in this gynecologic cancer, according to Emese Zsiros, MD, PhD, FACOG.
On February 10, 2026, the FDA approved pembrolizumab (Keytruda) as well as pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for use in combination with paclitaxel, with or without bevacizumab, for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express a PD-L1 combined positive score (CPS) of 1 or greater and who have received 1 or 2 prior systemic treatment regimens.1
The regulatory agency approved the PD-L1 IHC 22C3 pharmDx assay in conjunction with the regimen to determine patient eligibility for the treatment.
The approval was based on data from the phase 3 KEYNOTE-B96 trial (NCT05116189), which showed improved progression-free survival (PFS) and overall survival (OS) with the addition of pembrolizumab to paclitaxel with or without bevacizumab (n = 234) vs placebo plus paclitaxel with or without bevacizumab (n = 232) in patients with PD-L1–positive, platinum-resistant, recurrent ovarian cancer (PFS and OS: HR, 0.76; 95% CI, 0.62-0.93).2
“This is a [historic] moment in ovarian cancer because we had so many negative immuno-oncology [IO] clinical trials, and this is the first positive IO clinical trial and the first indication for pembrolizumab in ovarian cancer,” Zsiros said. “Our field is extremely excited. This is not necessarily an easy regimen [to receive] because it requires weekly administration of paclitaxel, but the results are very strong and scientifically sound. It is exciting for us to see a significant and clinically meaningful OS benefit in this very challenging [to treat] patient population.”
In an interview with OncLive®, Zsiros, chair of the Department of Gynecologic Oncology and the Shashi Lele, MD, Endowed Chair in Gynecologic Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, discussed how PD-L1 testing will be incorporated into everyday practice, how to interpret the magnitude of benefit seen in KEYNOTE-B96, and what this landmark approval means for biomarker-driven strategies in ovarian cancer.
A Turning Point in Platinum-Resistant Disease
- The FDA approved pembrolizumab for use in combination with paclitaxel, with or without bevacizumab, for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1, and who have received 1 or 2 prior systemic treatment regimens.
- The agency also approved the PD-L1 IHC 22C3 pharmDx assay as a companion diagnostic test to identify patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who may be eligible for treatment with pembrolizumab.
- Findings from the pivotal phase 3 KEYNOTE-B96 trial showed an improvement in OS and PFS with pembrolizumab plus paclitaxel with or without bevacizumab vs placebo plus paclitaxel with or without bevacizumab alone in patients with platinum-resistant, recurrent ovarian cancer.
OncLive: How should PD-L1 testing with the newly approved PD-L1 IHC 22C3 pharmDx companion diagnostic be integrated into routine clinical practice for platinum-resistant ovarian cancer?
Zsiros: This is a great question, and a very timely question, because PD-L1 in the past has not been a great biomarker in ovarian cancer, and clinically is not utilized to make treatment decisions. This is the first FDA approval that will require us to really take PD-L1 expression by CPS into account when we are sequencing treatment for platinum-resistant, recurrent ovarian cancer. In my clinic, at this point, we request testing for this biomarker for every patient [whether up front or at] the first time of recurrence. This is typically an in-house test. Most academic [institutions] or laboratories should be familiar with this platform since PD-L1 staining has been used for other disease [types] with pembrolizumab. We will be incorporating [this test] into our routine biomarker testing, so that we can get these results for every single one of our patients with ovarian cancer.
How do you interpret the magnitude of benefit with pembrolizumab plus paclitaxel with or without bevacizumab in the KEYNOTE-B96 trial? Which patient subgroups derived the greatest benefit from the pembrolizumab regimen?
When you look at the data that have been presented so far, the median PFS in the patients [with a] PD-L1 CPS of 1 or greater was 8.3 months [95% CI, 7.0-9.5] with the investigational regimen vs 7.2 months [95% CI, 6.2-8.1] in the control arm [HR, 0.76]. In the intention-to-treat [ITT] patient population, the median PFS was 8.3 months [95% CI, 7.2-8.6] with the pembrolizumab regimen vs 6.4 months [95% CI, 6.2-8.1] with the control regimen, which showed a 27% reduction in risk of progression [or death] for the cohort that received pembrolizumab.
The OS benefit that has been presented so far was only [seen] in the PD-L1–positive cohort.* The ITT cohort data [were] presented at the 2026 European Society of Gynaecological Oncology Congress. In the PD-L1–positive cohort, the median OS was approximately 18.2 months [95% CI, 15.3-21.3] with pembrolizumab vs 14.0 months [95% CI, 12.5-16.1] with placebo, roughly [translating to] a 4-month gain. The HR was 0.76, [translating to a] 24% reduction in the risk of death in this patient population.
What are the key considerations when you are deciding whether to add bevacizumab to this combination in terms of efficacy, toxicity, and costs, given that the approval encompasses pembrolizumab’s use with and without VEGF therapy?
Dr Nicoletta Colombo of the University of Milan presented data [from KEYNOTE-B96] at [the 2025 European Society for Medical Oncology Congress], and what we know so far is that the subgroup that received bevacizumab did not have improved PFS or OS in the interim analysis.
As far as when to add bevacizumab, it’s really going to come down to the treating physicians and the patients through mutual decision-making. There are some patients who may have ascites or some additional risk factors [that would affect that decision]. What we’ve learned so far from the interim analysis is that the regimen works [with or] without bevacizumab, and there is no detrimental effect in those patients who could not receive bevacizumab [because] we saw positive PFS and OS data in the weekly paclitaxel and pembrolizumab arm.
What immune-related adverse effects (irAEs) should clinicians proactively monitor with the pembrolizumab combination?
From a safety perspective, there were no new signals, and toxicities were consistent with what we would expect with the weekly paclitaxel and pembrolizumab combination. The irAEs were very familiar. We use pembrolizumab in other gynecologic cancers. The [toxicities] were very manageable, and there was nothing beyond what would be expected from the combination, so no new emerging or additive toxicities. Our treating physicians are very familiar with the weekly paclitaxel and bevacizumab combination, so [administering] this [combination] with pembrolizumab should [be able to be] integrated into routine clinical practice easily.
How will this FDA approval affect the relevance of biomarkers in the management of recurrent ovarian cancer?
Right now, there are a couple of biomarkers that are becoming [increasingly] important when it comes to sequencing therapies in recurrent ovarian cancer. We realize that the disease is no longer homogeneous at the time of recurrence, and the treatment selection is going to be more biomarker driven. Two of the biomarkers that we’re already utilizing are FRα expression and HER2 expression—those markers are clinically extremely relevant. Other biomarkers…being utilized mostly in the frontline maintenance setting are BRCA and homologous recombination–deficient signatures. But they become less relevant in the recurrent setting. At this point, we’re also using mismatch repair deficiency and tumor mutational burden [to signal candidacy for] single-agent checkpoint blockade in ovarian cancer. However, only 1% to 3% of our patients fall into this category, so this is a small subset.
[I see this approval changing] the treatment landscape for recurrent ovarian cancer [by making it] more biomarker driven. That’s what we’re going to see with PD-L1 becoming another biomarker that will help us strategize which regimen to pick first.
*Editor’s Note: This interview took place prior to the 2026 European Society of Gynaecological Oncology Congress.
References
- FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. FDA. February 10, 2026. Accessed March 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-paclitaxel-platinum-resistant-epithelial-ovarian-fallopian-tube-or
- Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: final analysis results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Presented at: 2026 European Society of Gynaecological Oncology Congress; February 26-28, 2026; Copenhagen, Denmark. Abstract BO2-1/526.
