MSD's anti-PD-1 immuno-oncology drug Keytruda (pembrolizumab) has won approval for cervical cancer in Korea, advancing the indication to locally advanced disease and raising expectations for its early treatment.

MSD Korea hosted a media seminar on Keytruda’s cervical cancer indication on Tuesday. Dr. Kim Yong-man, professor of obstetrics and gynecology at Asan Medical Center, spoke about cervical cancer, the unmet need, and data from the phase 3 trial of KEYNOTE-A18 in cervical cancer.

Keytruda was approved by the Ministry of Food and Drug Safety (MFDS) in April for treating patients with FIGO 2014 stage Ⅲ-ⅣA cervical cancer in combination with chemoradiotherapy. Stage Ⅲ is defined as tumor invasion of the lower third of the vagina or pelvic side wall, and infiltration of the tumor has caused hydronephrosis or renal insufficiency. Stage ⅣA is defined as tumor metastasis beyond the true pelvis to adjacent organs, such as the bladder or rectal mucosa.

The expanded indication allows Keytruda to be used in earlier stages than the original indication of PD-L1-positive (CPS≥1) persistent, recurrent, or metastatic cervical cancer.

Cervical cancer is a cancer of the female genital tract that develops in the cervix, the opening to the uterus. The primary risk factor is infection with the human papillomavirus (HPV) virus. Still, smoking, human immunodeficiency virus (HIV) infection, chlamydial infection, and long-term oral contraceptive use can also increase the risk of cervical cancer. According to the 2021 National Cancer Registry, cervical cancer ranked fifth in the prevalence of female cancers in Korea, with 62,204 cases.

Cervical cancer often recurs after treatment. Five to 20 percent of stage 1 and 2 cervical cancer patients who undergo surgery experience recurrence, and about 40 percent of locally advanced patients with advanced stages recur after treatment. The five-year (2017-2021) relative survival rate by stage is high at 94.4 percent for localized disease but drops to 74.1 percent for regional metastases and 27.8 percent for distant metastases.

Professor Kim explained that all this explains why aggressive treatment at an early stage is important to prevent recurrence and metastasis.

"Since chemoradiotherapy became the standard of care in the 2000s, many studies have been conducted to improve the survival rate of locally advanced patients, but it has not been resolved for 24 years,” Kim said. "The U.S. NCCN guidelines show that there are many different treatments and studies, and the clinical data from Keytruda may help unify these approaches."

The KEYNOTE-A18 trial enrolled 1,060 patients with lymph node-positive FIGO 2014 stage IB2-IIB cervical cancer (462 patients) who had not received prior cervical cancer treatment (radical surgery, radiation, or systemic therapy) and 596 patients with lymph node-positive or negative FIGO 2014 stage III-IVA (596 patients) and two patients with stage IVB. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

In a subanalysis of patients with stage III-IVA at FIGO 2014, 12-month progression-free survival (PFS) was 81 percent (95 percent CI, 75-85) in the Keytruda-chemoradiotherapy arm vs. 70 percent (95 percent CI, 64-76) in the placebo arm, resulting in a 41 percent reduction in the risk of disease progression and death compared to placebo (HR=0.59 [95 percent CI, 0.43-0.82]), which was the basis for U.S. Food and Drug Administration (FDA) approval earlier this year.

In the overall patient population, 24-month progression-free survival (PFS) was 68 percent (95 percent CI 62-73) in the Keytruda-chemoradiotherapy combination arm and 57 percent (95 percent CI, 51-63) in the placebo arm, resulting in a 30 percent reduction in the risk of disease progression and death in the Keytruda arm compared to placebo (HR=0.70 [95 percent CI, 0.55-0.89]). Twenty-four-month overall survival (OS) was 87 percent (95 percent CI, 82-91) in the Keytruda arm and 81 percent (95 percent CI, 75-86) in the placebo arm, resulting in a 27 percent reduction in the risk of death compared to placebo (HR=0.73 [95 percent CI, 0.49-1.07]).

However, the OS data are still preliminary and statistically incomplete.

"We expect to be able to disclose statistically robust evidence of OS improvement as early as this year before or after the European Society for Medical Oncology (ESMO) Congress, said Kim Yo-han, senior vice president of medical affairs at MSD Korea.