MSD's Keytruda Shows Potential to Transform Early-Stage Triple-Negative Breast Cancer Treatment Through Neoadjuvant and Adjuvant Strategy

At Merck & Co.’s (MSD) investor conference held this June, the company highlighted that a key strategic focus for its blockbuster PD-1 inhibitor Keytruda is its use as neoadjuvant and adjuvant therapy in patients with early-stage cancer. Currently, more than 100 ongoing clinical trials are evaluating Keytruda as a neoadjuvant or adjuvant treatment for early-stage cancers. At today’s ESMO Congress, the company announced the remarkable efficacy of Keytruda as a neoadjuvant/adjuvant therapy in patients with early-stage triple-negative breast cancer (TNBC), further demonstrating the potential of this development strategy. As company executives stated, efforts to unlock the full potential of Keytruda are still in their early stages!

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, characterized by a high recurrence rate within five years after diagnosis. Approximately 15–20% of breast cancer patients are diagnosed with TNBC. Due to the lack of expression of estrogen receptors, progesterone receptors, and HER2 receptors, therapies targeting these receptors demonstrate limited efficacy in treating this type of breast cancer.

Keytruda is a blockbuster PD-1 inhibitor developed by MSD, and it has received FDA approval for the treatment of more than 20 indications. In the pivotal clinical trial named KEYNOTE-522, Keytruda was used as neoadjuvant therapy in combination with chemotherapy to treat patients with TNBC before they underwent surgical treatment; the control group during the neoadjuvant phase received chemotherapy alone. During the post-surgical adjuvant therapy phase, these TNBC patients received Keytruda as adjuvant therapy, while the control group did not receive any treatment.

Trial results demonstrated that, in the neoadjuvant setting, Keytruda combined with chemotherapy significantly improved patients’ pathological complete response (pCR, defined as the absence of residual invasive cancer in the breast and nearby lymph nodes after surgery) compared with chemotherapy alone. The pCR rate was 64.8% in patients receiving the Keytruda–chemotherapy combination, versus 51.2% in the chemotherapy control group. Importantly, the clinical benefit of Keytruda as neoadjuvant therapy was independent of tumor PD-L1 expression.

With a median follow-up period of 15.5 months, Keytruda reduced the risk of disease progression during the neoadjuvant phase and recurrence during the adjuvant phase by 37% compared to the control group, thereby improving patients’ event-free survival (EFS). MSD also announced that the U.S. FDA has granted Breakthrough Therapy Designation to Keytruda, in combination with chemotherapy, as a neoadjuvant treatment for patients with high-risk early-stage triple-negative breast cancer (TNBC).

“This innovative clinical trial design marks the first use of Keytruda for both neoadjuvant and adjuvant therapy in patients with early-stage triple-negative breast cancer (TNBC),” said Dr. Roger M. Perlmutter, President of Merck Research Laboratories. “The results from the KEYNOTE-522 study are highly encouraging and have the potential to transform the treatment paradigm for TNBC!”

For immune checkpoint inhibitors, triple-negative breast cancer (TNBC) has remained a challenging cancer type to tackle. Currently, only Roche’s PD-L1 inhibitor, Tecentriq, has received FDA approval for the treatment of this cancer type. In May this year, Merck & Co., Inc. (MSD) announced that Keytruda, as a monotherapy, failed to meet the primary clinical endpoint in the treatment of patients with previously treated metastatic TNBC. However, the success of Keytruda as a neoadjuvant/adjuvant therapy in TNBC demonstrates that, despite its lack of efficacy in advanced metastatic disease, Keytruda still holds significant promise for the treatment of early-stage cancer!

▲Results from Multiple Pivotal Clinical Trials of Keytruda as Neoadjuvant/Adjuvant Therapy to Be Announced (Image Source: Reference [1])

Treating Early-Stage Cancer with Immunotherapy: A Research Direction Adopted by Multiple Pharmaceutical CompaniesThe success of this trial is expected to further promote the development and application of cancer immunotherapy in patients with early-stage cancer. Admittedly, patients receiving immunotherapy at an early stage of cancer must weigh the potential benefits against the side effects associated with the treatment. However, for those at high risk of recurrence, reducing future potential risks through early intervention is undoubtedly a powerful option for prolonging life and maintaining health.

References:

[1] Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Showed Statistically Significant Increase in Pathological Complete Response Versus Chemotherapy as Neoadjuvant Therapy in Early-Stage Triple-Negative Breast Cancer (TNBC). Retrieved September 29, 2019, from https://www.mrknewsroom.com/news-release/oncology/mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-statistically-significa

[2] Merck Provides Update on Phase 3 KEYNOTE-119 Study of KEYTRUDA® (pembrolizumab) Monotherapy in Previously-Treated Patients with Metastatic Triple-Negative Breast Cancer. Retrieved September 29, 2019, from https://www.mrknewsroom.com/news-release/oncology/merck-provides-update-phase-3-keynote-119-study-keytruda-pembrolizumab-monothe

[3] ESMO: Merck's Keytruda posts first-in-class victory in pre-surgery breast cancer. Retrieved September 29, 2019, from https://www.fiercepharma.com/pharma/esmo-merck-s-keytruda-posts-first-class-victory-pre-surgery-breast-cancer

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