Pembrolizumab Granted 4 Approvals in Japan for High-Risk TNBC, RCC, and More


Japan’s Ministry of Health, Labor and Welfare approved pembrolizumab for use in 4 indications, including high-risk, early-stage triple-negative breast cancer, stage IIB or IIC melanoma, adjuvant renal cell carcinoma, and recurrent/metastatic cervical cancer.

Japan’s Ministry of Health, Labor and Welfare approved pembrolizumab (Keytruda) both as a single agent and in combination with other drugs across several disease types, including in combination with neoadjuvant chemotherapy in hormone receptor–negative, HER2-negative triple-negative breast cancer (TNBC) at a high risk of recurrence; in adjuvant renal cell carcinoma (RCC) at a high risk of recurrence post-nephrectomy or nephrectomy and metastatic lesion resection; in combination with chemotherapy plus or minus bevacizumab (Avastin) for advanced or recurrent cervical cancer with no previous chemotherapy use; and adjuvant stage IIB or IIC fully resected melanoma, according to a press release from Merck.1

“Based on compelling data from our clinical trial program, [pembrolizumab] has become an important treatment option in Japan and now has 23 approved uses across 13 different types of cancer,” Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, said in the press release. “These four new approvals provide certain patients with advanced or recurrent cervical cancer, high-risk early-stage triple-negative breast cancer, renal cell carcinoma, and completely resected stage IIB and IIC melanoma the opportunity to be treated with [pembrolizumab.]”

The neoadjuvant TNBC combination regimen was approved based on the results of the phase 3 KEYNOTE-522 trial (NCT03036488), which demonstrated that the treatment regimen yielded a clinically meaningful improvement in event-free survival (EFS), as well as a 37% reduction in risk of progression, recurrence, second primary malignancy, or death (HR, 0.63; 95% CI, 0.48-0.82; P = .00031). Results from the phase 3 KEYNOTE-564 trial (NCT03142334) led to the approval of pembrolizumab monotherapy for RCC; patients treated with the agent had a statistically significantly improved disease-free survival vs placebo, as well as a 32% reduction in risk of recurrence or death.

Additionally, pembrolizumab in combination with chemotherapy and with or without bevacizumab was approved for advanced cervical cancer not amenable to curative treatment based on the phase 3 KEYNOTE-826 trial (NCT03635567), which highlighted a statistically significant overall survival (OS) benefit vs chemotherapy with or without bevacizumab; the reduction in risk of death was 33% (HR, 0.67; 95% CI, 0.54-0.84; P = .0003). Finally, the adjuvant single-agent pembrolizumab approval for stage IIB or IIC melanoma was based on results from the phase 3 KEYNOTE-716 trial (NCT03553836), which highlighted significantly prolonged recurrence-free survival interval for pembrolizumab monotherapy vs placebo and reduced risk of disease recurrence or death by 35% (HR, 0.65; 95% CI, 0.46-0.92; P = .00658).

Previously, the FDA had approved the same pembrolizumab regimens for high-risk early TNBC in July 2021, stage IIB and IIC resected melanoma in December 2021, adjuvant RCC in November 2021, and recurrent/metastatic cervical cancer in October 2021 based on the same trials.2-5


  1. Merck’s KEYTRUDA® (pembrolizumab) receives four new approvals in Japan, including in high-risk early-stage triple-negative breast cancer (TNBC). News release. Merck. September 27, 2022. Accessed September 28, 2022.
  2. FDA approves KEYTRUDA (pembrolizumab) for treatment of patients with high-risk early-stage triple-negative breast cancer in combination with chemotherapy as neoadjuvant treatment, then continued as single agent as adjuvant treatment after surgery. News release. Merck. July 27, 2021. Accessed September 28, 2022.
  3. FDA approves pembrolizumab for adjuvant treatment of stage IIB or IIC melanoma. News release. FDA. December 3, 2021. Accessed September 28, 2022.
  4. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. FDA. November 17, 2021. Accessed September 28, 2022.
  5. FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. FDA. October 13, 2021. Accessed September 28, 2022.
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