Merck announced results from the pivotal Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with external beam radiotherapy (EBRT) plus concurrent chemotherapy, followed by brachytherapy (also known as concurrent chemoradiotherapy) for newly diagnosed patients with high-risk locally advanced cervical cancer (stage 1B2-2B with lymph node-positive disease, and stage 3-4A with and without lymph node-positive disease). Results from the trial showed that KEYTRUDA in combination with concurrent chemoradiotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to concurrent chemoradiotherapy alone for these patients. The findings are being presented for the first time today at 10:45 a.m. ET during a late-breaking abstract proffered paper session at the European Society for Medical Oncology (ESMO) Congress 2023 (abstract #LBA38).
After a median follow-up of 17.9 months (range, 0.9-31.0), the KEYTRUDA regimen reduced the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.55-0.89]; p=0.0020) versus concurrent chemoradiotherapy alone in these patients. Median PFS was not reached in either group. The 24-month PFS rate was 67.8% for patients who received the KEYTRUDA regimen compared to 57.3% for those who received concurrent chemoradiotherapy alone. In addition to an improvement in PFS, a favorable trend in overall survival (OS), the trial’s other primary endpoint, was observed for the KEYTRUDA regimen versus concurrent chemoradiotherapy alone (HR=0.73 [95% CI, 0.49-1.07]); with only 103 events across both groups, these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial is continuing, and follow-up of OS is ongoing. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.
“Cervical cancer is the fourth most common cancer in women worldwide; however, over the past two decades, new treatment advances have been limited for patients diagnosed with locally advanced disease,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “These positive results from the KEYNOTE-A18 trial demonstrate the potential of KEYTRUDA in combination with concurrent chemoradiotherapy as a new treatment option for patients with high-risk cervical cancer, building on the established role of KEYTRUDA for certain patients with advanced cervical cancer and our research efforts in earlier stages of disease.”
“This is the first phase 3 study in which an immunotherapy has demonstrated an improvement in progression-free survival in this patient population compared to standard of care,” said professor Domenica Lorusso, the study’s overall principal investigator, lead investigator for ENGOT and associate professor of Obstetrics and Gynecology at the Catholic University of Rome. “The results of this trial, finding the KEYTRUDA regimen reduced the risk of disease progression or death by 30% compared to concurrent chemoradiotherapy alone, are compelling, especially considering newly diagnosed patients with high-risk locally advanced cervical cancer have not seen an advance in treatment options in 20 years.”
“Patients diagnosed with locally advanced cervical cancer face a poor prognosis and limited treatment options,” said Dr. Bradley Monk, oncologist and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine. “These results demonstrate that by moving an immunotherapy regimen to earlier stages of cervical cancer, we have the potential to improve outcomes for these patients compared to the current standard of care.”
Merck previously announced that based on these positive results, the U.S. Food and Drug Administration (FDA) has granted priority review for a supplemental Biologics License Application (sBLA) for KEYTRUDA in combination with concurrent chemoradiotherapy for the treatment of newly diagnosed patients with high-risk locally advanced cervical cancer. The FDA has set a Prescription Drug User Fee Act, or target action, date of January 20, 2024. The results are also being discussed with regulatory authorities worldwide.
In the U.S., KEYTRUDA has two approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
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