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September 18, 2021
3 minutes to read
Source / Disclosures
Published by:
Colombo N, et al. Abstract LBA2_PR. Presented at: Congress of the European Society of Medical Oncology (virtual meeting); September 17-21, 2021.
Disclosures: Merck Sharp & Dohme Corp. funded this study. Monk reports relationships with Merck, Roche / Genentech and several other pharmaceutical companies. Please see the summary for all relevant financial information from other researchers.
Adding pembrolizumab to chemotherapy, with or without bevacizumab, significantly improved PFS and OS in women with persistent, recurrent, or metastatic cervical cancer, study results showed. randomized phase 3 KEYNOTE-826.
The combination, which has demonstrated clinically significant improvement regardless of PD-L1 tumor expression, may represent a new standard of care for this patient population, according to results presented at the ESMO Virtual Congress.
“This is great news for patients”, Bradley J. Monk, MD, FACS, FACOG, professor at Creighton University School of Medicine and University of Arizona College of Medicine, director of gynecologic oncology research at the US Oncology Network and co-director of the Gynecologic Oncology Group, Healio said. “In more than 2 decades, we have gone from no chemotherapy to chemotherapy, chemotherapy and bevacizumab, and now to chemotherapy, bevacizumab and pembrolizumab.”
KEYNOTE-826 included 617 women with persistence, recurrence or metastasis Cervical cancer that had not been treated with systemic chemotherapy and were not suitable for curative treatment. Researchers randomly assigned 308 women (median age, 51 years) to 200 mg of pembrolizumab (Keytruda, Merck) and 309 women (median age, 50 years) to placebo every 3 weeks for up to 35 cycles. All the women also received chemotherapy with paclitaxel and cisplatin or carboplatin, and 63.6% in the pembrolizumab group and 62.5% in the placebo group also received bevacizumab (Avastin, Genentech). The researchers stratified the women based on metastatic status at diagnosis, intended use of bevacizumab, and combined positive PD-L1 score (CPS).
Bradley J. Monk
Investigator-assessed PFS according to RECIST version 1.1 and OS served as primary endpoints, tested sequentially in 548 women with a PD-L1 CPS of 1 or greater, the all-comer population and 317 women with a CPS PD-L1 of 10 or greater.
Results of the first planned interim analysis, presented during ESMO and published simultaneously in New England Journal of Medicine, showed a median PFS of 10.4 months in the three groups with pembrolizumab and chemotherapy versus 8.2 months with placebo and chemotherapy for women with a CPS PD-L1 of 1 or greater (HR = 0.62; CI at 95%: 0.5-0.77) and all women (HR = 0.65; 95% CI, 0.53-0.79) and 8.1 months for women with a CPS PD-L1 of 10 or greater (HR = 0.58; 95% CI, 0.44-0.77). The rate of 12-month PFS in all women was 44.7% with the pembrolizumab regimen versus 33.5% with the placebo (HR = 0.65; 95% CI: 0.53-0.79), with similar rates among PD-L1 subgroups.
The median OS in the population of all arrivals was 24.4 months with pembrolizumab versus 16.5 months with placebo (HR = 0.67; 95% CI: 0.54-0.84), which Monk described it as “a huge progressive leap”. Median OS was not achieved in any of the PD-L1 subgroups.
24-month ILI rates were 53% vs. 41.7% for women with a PD-L1 CPS of 1 or greater, 50.4% vs. 40.4% for all women, and 54.4% vs. 44 , 6% for women with a PD-L1 CPS of 10 or more.
The researchers observed the survival benefit regardless of the use of bevacizumab.
“Bevacizumab should be used when it can,” Monk said. “If you look at the risk ratio when bevacizumab is added, it’s better enough to justify its use.”
Adverse events of grade 3 or higher occurred in 81.8% of the pembrolizumab group and 75.1% of the placebo group and included anemia (30.3% vs. 26.9%) and neutropenia (12.4% against 9.7%). Adverse events leading to discontinuation of all treatment occurred in 37.5% of patients in the pembrolizumab group versus 26.5% of patients in the placebo group and 5.9% versus 4.9% for all treatments.
“During the first interim analysis, the sponsor and the data security oversight committee said, ‘Wow, that’s a big deal.’ You have improved response rate, progression-free survival, overall survival, and even patient-reported outcomes seem more favorable, ”Monk told Healio. “So not only are patients living longer… they might even live better. And these are young women in their forties and fifties. “
Monk said KEYNOTE-826 will quickly launch pembrolizumab as the global standard of care in first-line metastatic cervical cancer.
“The next step will be to add checkpoint inhibitors to chemotherapy and radiation therapy with the goal of curing more patients. This kind of has already been validated in the PACIFIC trial with durvalumab [Imfinzi, AstraZeneca] in lung cancer, then we’re getting there. Ultimately, the real solution – just like in COVID – is to get vaccinated. “
The references:
- Colombo N, et al. Abstract LBA2_PR. Presented at: Congress of the European Society of Medical Oncology (virtual meeting); September 17-21, 2021.
- Colombo N, et al. NOT English J Med. 2021; doi: 10.1056 / NEJMoa2112435.
Perspective
Stephanie V. Blank, MD
KEYNOTE-826 changes the practice. The study shows an impressive increase in OS and PFS for those women who in the past had few options. Adding pembrolizumab to chemotherapy reduced the risk of death by 33%, prolonged survival by 8 months, and reduced the likelihood of disease progression or death by 35%.
KEYNOTE-826 is notable for moving immunotherapy earlier in the course of treatment for people with advanced or recurrent cervical cancer – first-line for systemic treatment – and is the first study to show similarly positive results for anti-PD-L1 treatment plus chemotherapy in this setting. It also confirms the signal observed for pembrolizumab in the second-line treatment of advanced or recurrent cervical cancer. Interestingly, PD-L1 was not a predictive biomarker.
The ideal would be to answer the question whether the improvement seen with the addition of pembrolizumab to paclitaxel / carboplatin requires bevacizumab. Bevacizumab may increase the immunogenicity of the tumor, but if it does not add to the improvements in survival shown in this study, we could avoid using four drugs when three will suffice. This could alleviate some of the financial toxicity associated with this diet.
But the take-home message here is that pembrolizumab, when added to chemotherapy with or without bevacizumab as a first-line systemic treatment for advanced or recurrent cervical cancer, improves survival and marks a breakthrough in cancer. the domain. I applaud and thank the authors as well as the 617 patients and their families.
Stephanie V. Blank, MD
Mount Sinai Health System
Disclosures: Blank reports no relevant financial disclosure.
Perspective
Mansoor Raza Mirza, MD
[KEYNOTE-826 showed] a statistically significant advantage in the intention-to-treat population, the treatment is tolerated fairly well, and I would say it should be – maybe not, like Dr. [Colombo] says – the new standard of care for our patients. However, other questions arise. Is this combination effective in primary metastatic disease? In a population without a biomarker? In adenocarcinoma? Administered without bevacizumab? My take-home message to you would be that pembrolizumab plus chemotherapy with bevacizumab in a biomarker positive population will be the new standard of care for women with persistent, recurrent, or possibly metastatic cervical cancer. primary.
Mansoor Raza Mirza, MD
Copenhagen University Hospital
Congress of the European Society of Medical Oncology
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