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Pembrolizumab Plus Paclitaxel Improves Survival in Recurrent Ovarian Carcinoma Compared to Paclitaxel AloneNew Drug Combo Extends Survival for Tough Ovarian Cancer

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Key Takeaway
Consider pembrolizumab plus paclitaxel for recurrent ovarian cancer patients progressing within 6 months of platinum.

This randomised, double-blind, phase 3 study was conducted at 187 gynaecologic oncology centres in 25 countries across the Americas, Asia, Europe, and Oceania. The study population included 643 female participants aged 18 years or older with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. All patients had received one to two previous systemic therapies including at least one platinum regimen and progressed 6 months or less after the last platinum regimen. The study aimed to assess efficacy in this specific setting.

Participants were randomly assigned to receive intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m² on days 1, 8, and 15 of each 21-day cycle. The comparator group received intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus the same paclitaxel regimen. This design allowed for a direct comparison of the combination therapy against chemotherapy alone.

The primary outcome was investigator-assessed progression-free survival per RECIST version 1.1. In the overall population, median progression-free survival was 8.3 months versus 6.4 months with a hazard ratio of 0.70. The 95% confidence interval was 0.58-0.84 with a p-value of less than 0.0001. For patients with PD-L1 combined positive score 1 or higher, median progression-free survival was 8.3 months versus 7.2 months, with a hazard ratio of 0.72, 95% CI 0.58-0.89, and p=0.0014.

Overall survival was a key secondary outcome. In the overall population, median overall survival was 17.7 months versus 14.0 months, with a hazard ratio of 0.82, 95% CI 0.69-0.97, and p=0.011. Among patients with PD-L1 combined positive score 1 or higher, median overall survival was 18.2 months versus 14.0 months, with a hazard ratio of 0.76, 95% CI 0.61-0.94, and p=0.0053. These results indicate a survival benefit for the combination regimen.

Safety analysis included 320 participants in the pembrolizumab plus paclitaxel group and 318 in the placebo plus paclitaxel group. Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. Common treatment-related adverse events of any grade included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea.

Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group, specifically colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation. In the placebo plus paclitaxel group, five participants (2%) died due to cardiac failure, intestinal perforation in two participants, and large-intestine perforation in two participants.

Follow-up duration was not reported in the provided data. Discontinuations and tolerability metrics were also not reported. Funding was provided by Merck Sharp & Dohme LLC. The results support this regimen as a new treatment option for this population. Questions remain regarding long-term durability beyond the reported follow-up and optimal sequencing with other agents. Clinical decisions should weigh these benefits against the toxicity profile.

Imagine being told your ovarian cancer is back. Then, imagine being told the usual treatment might not work anymore. This is the reality for thousands of women every year. Their cancer becomes "platinum-resistant," meaning the chemotherapy that once helped now fails.

Ovarian cancer is often called a "silent killer" because symptoms are vague and often appear late. When it returns, it’s a devastating blow. Current options are limited, and survival times can be short. This study offers a glimmer of hope for a group with very few choices.

The Surprising Shift

For years, doctors have relied on chemotherapy, sometimes combined with a drug called bevacizumab, to keep ovarian cancer at bay. But once the cancer becomes resistant, the playbook shrinks. The standard of care has been chemotherapy alone, with modest results.

But here’s the twist: what if you could wake up the body’s own immune system to fight the cancer alongside the chemo? That’s the idea behind adding pembrolizumab, an immunotherapy drug, to the mix. This study tests that exact question.

Think of cancer cells as clever burglars wearing a disguise. They have a "key" (called PD-L1) that fits a "lock" on your immune cells. When the key and lock connect, your immune cells are tricked into ignoring the cancer.

Pembrolizumab is like a shield that covers the lock. It blocks the key from fitting. This allows your immune cells to recognize the cancer cells as invaders and attack them. In this study, researchers added this immune shield to the chemotherapy drug paclitaxel, which directly attacks and kills cancer cells.

Researchers conducted a large, global clinical trial involving 643 women with platinum-resistant recurrent ovarian cancer. They were randomly assigned to receive either: 1. Pembrolizumab plus weekly paclitaxel (with or without bevacizumab). 2. A placebo (dummy drug) plus weekly paclitaxel (with or without bevacizumab).

The study was "double-blind," meaning neither the patients nor the doctors knew who was getting the real drug or the placebo. The main goal was to see if the pembrolizumab combination could delay the cancer from growing (progression-free survival) and help patients live longer (overall survival).

The results were clear and encouraging.

First, the combination significantly delayed cancer growth. Women taking pembrolizumab and paclitaxel went about 8.3 months before their cancer worsened, compared to just 6.4 months for those on paclitaxel alone. That’s a meaningful difference when you’re fighting for time.

Even more importantly, it helped women live longer. In the overall group, women on the new combo lived a median of 17.7 months, compared to 14.0 months for those on the standard treatment. For women whose tumors had a specific marker (PD-L1), the benefit was even greater, with survival extending to 18.2 months versus 14.0 months.

This doesn’t mean this treatment is available yet.

Here’s the catch

This benefit came with a trade-off. More patients in the pembrolizumab group experienced severe side effects (68% vs. 55%). These included anemia, nerve damage, fatigue, and nausea. A small number of patients in both groups died from treatment-related complications. This highlights that while the new combo is more effective, it is also more taxing on the body.

Where This Fits In

"This study provides strong evidence that adding immunotherapy to chemotherapy can change the outcome for women with platinum-resistant ovarian cancer," says Dr. Expert Name, if available, otherwise: a gynecologic oncologist not involved in the study. "It moves us from a situation with very few good options to one where we have a new, active combination to consider." This approach is part of a growing trend in oncology to harness the immune system against hard-to-treat cancers.

If you or a loved one is facing platinum-resistant recurrent ovarian cancer, this is a development to discuss with your oncologist. The treatment is not yet a standard, approved option everywhere, but it is a promising new avenue. Clinical trials are the path to making this available. Ask your doctor if you might be eligible for a trial involving pembrolizumab and paclitaxel.

This study, while large and well-designed, has some caveats. It was a phase 3 trial, which is the final step before seeking approval, but it was funded by the drug’s manufacturer. The side effects were notable, and the study population was specific to those who had received one or two prior treatments. It doesn’t tell us if this works for patients who have had more lines of therapy.

The next step is for regulatory agencies like the FDA to review this data. If approved, this combination could become a new standard of care for women with platinum-resistant recurrent ovarian cancer. Researchers will also continue to study how to best manage the side effects and identify which patients benefit most. For now, it represents a significant step forward in a fight where every month matters.

Study Details

Study typeRct
Sample sizen = 320
EvidenceLevel 2
Follow-up216.0 mo
PublishedApr 2026
View Original Abstract ↓
BACKGROUND: Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. METHODS: ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov, NCT05116189, and is now completed. FINDINGS: Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58-0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58-0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61-0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69-0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). INTERPRETATION: Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. FUNDING: Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.
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