Merck's Keytruda Plus Chemotherapy Outperforms Roche's Tecentriq Combo in Triple-Negative Breast Cancer, Highlighted at SABCS

Compiled by Hemingway

At the recently held 43rd San Antonio Breast Cancer Symposium (SABCS), MSD announced the latest Phase III clinical data on Keytruda in combination with chemotherapy for the treatment of triple-negative breast cancer (TNBC).

Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancers. It specifically refers to breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). This is an aggressive form of breast cancer characterized by rapid progression, poor prognosis, high recurrence rates, and a 5-year survival rate of less than 15%.

Clinical data from the KEYNOTE-355 trial (NCT02819518) demonstrate that Keytruda can be combined with any currently approved chemotherapy regimen, leveraging the benefits of combination therapy for the treatment of triple-negative breast cancer. In contrast, Roche’s Tecentriq previously failed in clinical trials evaluating its combination with the chemotherapy agent paclitaxel.

The addition of Keytruda to the chemotherapy drug paclitaxel reduced the risk of disease progression or death by 67% in patients with previously untreated metastatic triple-negative breast cancer (TNBC) whose tumors expressed the biomarker PD-L1 with a Combined Positive Score (CPS) of at least 10.

When used in combination with Bristol Myers Squibb’s Abraxane or albumin-bound paclitaxel (nab-paclitaxel), the addition of Keytruda reduced the risk by 43% compared to chemotherapy alone; when combined with gemcitabine/carboplatin, the risk was reduced by 23%. Due to its outstanding performance in the KEYNOTE-355 trial, Keytruda received accelerated approval from the FDA in November for use in combination with any of the aforementioned three chemotherapy regimens.

According to Roy Baynes, Chief Medical Officer and Head of Global Clinical Development at MSD, the 67% significant difference observed in the Keytruda plus paclitaxel subgroup, along with the statistically or clinically meaningful improvement in progression-free survival across the three trial groups, demonstrates the substantial value of Keytruda-based combination therapy in the treatment of PD-L1-high triple-negative breast cancer. Moreover, this effect appears to be independent of chemotherapy, which marks a distinct departure from previous findings.

However, the first checkpoint inhibitor to enter the indication landscape for triple-negative breast cancer (TNBC) was not MSD’s Keytruda, but rather Roche’s PD-L1 inhibitor Tecentriq. Based on the results of the Phase III clinical trial IMpassion130, in patients with metastatic TNBC whose PD-L1-stained tumor-infiltrating immune cells covered at least 1% of the tumor area, Tecentriq plus Abraxane significantly reduced the risk of disease progression or death by 40% compared with Abraxane alone.

However, further follow-up study data presented by Roche at this year’s European Society for Medical Oncology (ESMO) Congress indicated that the combination therapy of Tecentriq plus paclitaxel was inferior to chemotherapy alone in prolonging patient survival. As a result, the U.S. Food and Drug Administration (FDA) issued a warning advising physicians against using the Tecentriq plus paclitaxel regimen in the treatment of triple-negative breast cancer (TNBC). Consequently, Roche has limited its promotion of Tecentriq to the combination of Tecentriq with Abraxane. In contrast, Merck can promote the efficacy of Keytruda for triple-negative breast cancer across three chemotherapy regimens.

For physicians and patients, having diverse treatment options is crucial. Paclitaxel, one of the most commonly used chemotherapy agents, is widely utilized, whereas nab-paclitaxel (Abraxane) is predominantly used in the United States. Platinum-based chemotherapy regimens have now been proven to be the most effective option for the treatment of triple-negative breast cancer.

Currently, the approval of Keytruda for triple-negative breast cancer is limited to patients with tumors exhibiting a PD-L1 Combined Positive Score (CPS) greater than 10. At this year’s SABCS meeting, Merck also presented data for patients with a PD-L1 score of 1 or higher. In this patient subgroup, Keytruda plus chemotherapy reduced the risk of disease progression or death by only 26%, a result that was not statistically significant. Follow-up trials are currently underway to determine whether Keytruda-based combination therapy can extend patient survival.

In addition, MSD has a pending FDA approval for the use of Keytruda in combination with platinum-based chemotherapy in the perioperative setting for high-risk early-stage triple-negative breast cancer (TNBC), with the decision date scheduled for March 29, 2021.

Reference Source: SABCS: Merck’s Keytruda Outshines Roche’s Tecentriq with Chemo Combo Win in Triple-Negative Breast Cancer