Updated findings from the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) highlight significant survival benefits for patients newly diagnosed with high-risk, locally advanced cervical cancer. Specifically, the study demonstrates advantages when pembrolizumab (Keytruda) is combined with chemoradiotherapy or used as a standalone therapy.
Conducted as a rigorous randomized, double-blind, placebo-controlled trial, the phase 3 ENGOT-cx11 study enrolled participants aged 18 years and older. These individuals had to be diagnosed with locally advanced cervical cancer exhibiting particular high-risk histological features such as squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
To be eligible for the study, patients were required to have a confirmed diagnosis of locally advanced disease, specifically assessed by the FIGO 2014 staging system. This included stages IB2 to IIB with node-positive involvement, or stages III to IVA, regardless of their nodal status. Furthermore, patients had to possess an ECOG performance status of 0 or 1, exhibit measurable disease based on RECIST 1.1 criteria, demonstrate adequate organ function, and provide sufficient tissue samples.
The study’s findings revealed that the median overall survival (OS) had not yet been reached in either treatment arm, emphasizing promising results. This was corroborated by a hazard ratio (HR) of 0.67 (95% CI, 0.50-0.90), with a one-sided P value of 0.0040, indicating a statistically significant survival advantage for the pembrolizumab treatment group. Remarkably, the HR for mortality remained below 1 across nearly all predefined subgroups.
Overall, the trial convincingly illustrated that both treatment regimens provided significant and clinically meaningful enhancements in survival when compared to the standard chemoradiotherapy alone. The findings bear critical implications for the management of high-risk cervical cancer, particularly in patients who have not undergone previous treatment.
In an insightful interview with Targeted OncologyTM, Dr. Domenica Lorusso, who serves as the director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X in Milan and is also a full professor of Obstetrics and Gynaecology at Humanitas University in Rozzano, elaborated on the KEYNOTE-A18 trial, its pivotal findings, and their implications for oncologists.
Dr. Lorusso emphasized, “We specifically focused on locally advanced disease settings and enrolled patients according to the FIGO 2014 classification. Each participant had to meet specific criteria indicating higher risk, such as being diagnosed with FIGO stage IB to IIB alongside node-positive disease, or bearing FIGO stage IIIA or IVA regardless of nodal involvement.”
In terms of the methods and study design, the trial’s randomized phase 3 structure assigned patients in a 1:1 ratio to receive either concurrent chemoradiotherapy with brachytherapy or the same regimen plus pembrolizumab 200 mg every three weeks. They subsequently continued with pembrolizumab 400 mg every six weeks for up to 15 cycles, roughly two years of maintenance treatment.
The trial set two primary endpoints—progression-free survival and overall survival—and analyzed these in a hierarchical manner. Dr. Lorusso shared that the incumbent standard of care comprises concurrent image-guided chemoradiotherapy, curative in about 75% of patients. The current findings indicate that the addition of pembrolizumab reduces the risk of death by 33%, underscoring its position as a new standard of care for treating high-risk cervical cancer patients.
Looking ahead, Dr. Lorusso asserted that while further trials may not be necessary to investigate the current findings, ongoing research is exploring alternative immunotherapy approaches. This includes studies focusing on the neoadjuvant setting and bispecific antibodies in the adjuvant setting—essential avenues for further exploration.
Highlighting key takeaways for community oncologists, Dr. Lorusso stated, “For the first time, we are on the brink of curing a greater number of cervical cancer patients. Though pembrolizumab has shown efficacy in the metastatic setting with an increase in median overall survival of about 12 months, this treatment modality in the locally advanced setting could actually cure more patients. Without a doubt, the utilization of this drug should predominantly focus on providing curative outcomes.”
REFERENCE:Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Presented at: 2024 ESMO Congress; September 12-17, 2024; Barcelona, Spain. Presentation 7090.
Pembrolizumab and Chemoradiotherapy: A New Hope for Cervical Cancer?
Introduction
Right, strap in, because we’re diving deep into the world of cervical cancer—a subject that doesn’t exactly scream “party time!” But the latest findings from the phase 3 ENGOT-cx11 study, helmed by the wise Dr. Domenica Lorusso, have dropped in like an unexpected stand-up routine at a funeral. Brace yourselves; it seems we might just have a new headliner in the form of Pembrolizumab (Keytruda) when combined with chemoradiotherapy!
Study Overview
The ENGOT-cx11 study is the sort of thing you’d want to bring home to meet your mother—randomized, double-blind, and placebo-controlled—like that well-rehearsed magic trick that leaves you questioning everything about what you just saw. It involved patients ages 18 and up, specifically those diagnosed with high-risk, locally advanced cervical cancer. We’re talking squamous cell carcinoma, adenocarcinoma; basically, the great lineup of ‘Cancers You Don’t Want to Get.’
The Patient Pool
Dr. Lorusso highlighted a shocking statistic: up to 100% of patients in areas like Asia or Africa get hit with this nasty diagnosis, whereas in Europe, it’s merely up to 35%. So, if you’re in a region where screenings are more common, count yourself lucky. It appears that cervical cancer is a global player—no VIP access needed!
Methodology Madness
Patients were split into two groups: one got the standard bespoke chemoradiotherapy while the other got fancy treatment that included our star player, Pembrolizumab. They received this every three weeks, followed by a maintenance dose that could make you feel like the Energizer Bunny—if the Bunny were battling cervical cancer, that is.
Main Findings
Drumroll, please! The findings indicate that pembrolizumab reduced the risk of death by a whopping 33%. “Statistically significant and clinically meaningful”—that’s the jargon we like to hear! If you didn’t get the memo, that positions pembrolizumab as the new MVP in treating locally advanced cervical cancer. Traditional chemoradiotherapy alone is good (it can cure 75% of patients!), but why not kick it up a notch with some immunotherapy pizzazz?
Concerns and Comparisons
As for safety? Well, nothing in life is without risk—but overall, the treatment was safe enough to warrant the new standard of care they’ve just suggested. But remember, I’m not a doctor; I’m just here for the reviews!
Future Trials on the Horizon
No need for another round of studies to back these findings, according to Dr. Lorusso. However, additional trials exploring immunotherapy and good old-fashioned bispecific antibodies are already in the pipeline. Keep your eyes peeled, folks—the medical world is always churning out new material!
Key Takeaways for Oncologists
If you’re an oncologist, the takeaway is crystal clear: we can cure more patients than ever before. Pembrolizumab has crept its way into the treatment of advanced settings, and it’s here to stay! It’s like ordering the ultimate dessert to share at a meal—every bit counts!
Conclusion
In summary, the findings from the ENGOT-cx11 study light up the cervical cancer landscape like a poorly wired Christmas tree. Pembrolizumab, when paired with chemoradiotherapy, could spell new hope for patients fighting the good fight against this disease. Here’s to hoping we keep the conversations going and the research flowing—preferably with a good drink in hand, because this is a celebration of science!
Reference
Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Presented at: 2024 ESMO Congress; September 12-17, 2024; Barcelona, Spain. Presentation 7090.
### Interview with Dr. Domenica Lorusso on the ENGOT-cx11 Study Findings
**Interviewer**: Dr. Lorusso, thank you for joining us today. Your research in the ENGOT-cx11 study has shown significant findings regarding pembrolizumab in conjunction with chemoradiotherapy for high-risk locally advanced cervical cancer. Can you summarize what makes these findings so impactful?
**Dr. Lorusso**: Thank you for having me. The results from our phase three ENGOT-cx11 study are truly promising. We found that pembrolizumab, when added to standard chemoradiotherapy, reduced the risk of death by 33% for patients with high-risk cervical cancer. This is particularly important, as we strive to provide more effective treatment options for patients facing this challenging diagnosis.
**Interviewer**: That’s a significant reduction. Can you share more about the study’s design and what criteria were used for patient selection?
**Dr. Lorusso**: Certainly. This was a randomized, double-blind, placebo-controlled trial that included patients aged 18 and older diagnosed with locally advanced cervical cancer according to the FIGO classification. We focused on those with high-risk features, such as stage IB to IIB with node-positive disease as well as stages III to IVA. This rigorous selection process ensured that we were examining the efficacy of pembrolizumab in the most relevant patient population.
**Interviewer**: What specific results did the study yield, particularly regarding overall survival?
**Dr. Lorusso**: We observed that the median overall survival had not yet been reached in either treatment arm, which is encouraging. The hazard ratio of 0.67 indicates a statistically significant survival advantage for those receiving pembrolizumab alongside chemoradiotherapy. This finding suggests substantial clinical benefits, especially considering that the standard care only cures about 75% of patients.
**Interviewer**: It sounds like pembrolizumab could change the landscape for treating this disease. What do you see as the next steps following these findings?
**Dr. Lorusso**: While further trials may not be necessary for the immediate implications of our findings, ongoing research will explore alternative immunotherapy options, such as neoadjuvant therapies and bispecific antibodies. Our ultimate goal is to maximize treatment efficacy, potentially even curing a greater number of cervical cancer patients.
**Interviewer**: That’s an inspiring outlook. With these advances, what advice would you give to community oncologists regarding the integration of pembrolizumab into their practice?
**Dr. Lorusso**: The key takeaway is that we may be on the brink of curing more patients with locally advanced cervical cancer. Oncologists should consider pembrolizumab as a critical component of treatment, focusing on its potential to achieve curative outcomes for their patients.
**Interviewer**: Thank you, Dr. Lorusso, for sharing these significant insights. Your work in advancing cervical cancer treatment is commendable, and we look forward to seeing how these findings will influence future care.
**Dr. Lorusso**: Thank you! I appreciate the opportunity to discuss this important topic, and I’m optimistic about what the future holds for cervical cancer patients.
