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Trial Results Spark Talk of Curing More Metastatic Cervical Cancers

— Adding pembrolizumab to standard care extends overall survival by a year

MedpageToday

CHICAGO -- Overall survival (OS) in advanced cervical cancer improved significantly with the addition of pembrolizumab (Keytruda) to standard therapy, irrespective of PD-L1 expression status, updated results from a randomized trial showed.

Patients with PD-L1-positive tumors had a median OS of 28.6 months with the immune checkpoint inhibitor versus 16.5 months for those who received bevacizumab (Avastin) and chemotherapy. An all-comer analysis yielded similar results, as patients had a median OS of 26.4 months with pembrolizumab and 16.8 months without it.

"This is a transformational result," said Bradley Monk, MD, of the University of Arizona College of Medicine-Phoenix, during a press briefing prior to the American Society of Clinical Oncology (ASCO) annual meeting. "In the 90% of patients that express PD-L1, when pembrolizumab was added to chemotherapy with or without bevacizumab, there was a 40% difference in survival at any given point along the [survival] curve. Pembrolizumab can improve survival in these young women suffering from this terrible disease by more than a year."

"If you add the 10% that did not have the biomarker, the all-comer result, the hazard ratio was 0.63 and the difference is 9.6 months but still clinically relevant, statistically significant, and becoming now the standard of care," he added.

The findings confirmed the preliminary report from the study, showing an 8-month difference in OS in favor of adding the immune checkpoint inhibitor to chemotherapy with or without bevacizumab. The results supported of the pembrolizumab combination as first-line therapy for advanced cervical cancer, though only in PD-L1-positive patients.

KEYNOTE-826 involved 617 patients with previously untreated recurrent, persistent, or metastatic cervical cancer. Patients received standard platinum-based chemotherapy with or without bevacizumab and were randomized to pembrolizumab or placebo. The trial had dual primary endpoints of progression-free survival (PFS) and OS.

The preliminary analysis of the PD-L1-positive population (combined positive score ≥1) showed a median PFS of 10.4 months with the addition of pembrolizumab versus 8.2 months without it. Median OS at the time was 24.4 versus 16.5 months.

With additional follow-up (median of 39.1 months), the survival difference favoring pembrolizumab remained unchanged in the PD-L1-positive subgroup (HR 0.60, 95% CI 0.49-0.74, P<0.0001). The 24-month OS rate was 53.5% with pembrolizumab and 39.4% without it.

The all-comer analysis showed a median OS of 26.4 months with pembrolizumab and 16.8 months with placebo, which remained statistically significant (HR 0.63, 95% CI 0.52-0.77, P<0.0001). The landmark analysis showed a 24-month OS rate of 52.1% versus 38.7%.

No new safety signals emerged in the interval between the first and final analyses.

"Is it possible to cure a widely metastatic cancer?" said Monk. "I think it probably is. I can't believe that in my lifetime, we have sort of figured out -- and it's not enough -- that we can actually cure some patients, and if not cure, at least have them live a long time."

ASCO chief medical officer Julie Gralow, MD, agreed with Monk's assessment about advances in treating metastatic disease, but with a caveat.

"In my long career as a breast medical oncologist, I'm pretty sure we cured some metastatic breast cancer and definitely had some patients who lived out their normal lifespan and died of something else after decades," said Gralow, who moderated the press briefing. "But the definition of cure, sadly in these situations, is that you die of something else without evidence of disease. So we certainly need to do better and be better able to use the word cure."

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined ľֱ in 2007.

Disclosures

The study was supported by Merck.

Monk disclosed relationships with Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono/Merck, Genmab/Seattle Genetics, GOG Foundation, Gradalis, ImmunoGen, Iovance Biotherapeutics, Karyopharm Therapeutics, Macrogenics, Merck, Mersana, Myriad Pharmaceuticals, Novartis, Novocure, OncoC4, Pfizer, Pieris Pharmaceuticals, Puma Biotechnology, Regeneron, Roche/Genentech, Sorrento Therapeutics, TESARO/GSK, US Oncology, Vascular Biogenics, Advaxis, Array BioPharma, Janssen, Lilly, Morphotek, and NuCana.

Primary Source

American Society of Clinical Oncology

Monk BJ, et al "Pembrolizumab + chemotherapy versus placebo + chemotherapy for persistent, recurrent, or metastatic cervical cancer: Final overall survival results of KEYNOTE-826" ASCO 2023; Abstract 5500.