At the European Society for Medical Oncology Congress on September 13–17, promising results from the Phase III KEYNOTE-522 study involving MSD's neoadjuvant Keytruda (pembrolizumab) plus chemotherapy followed by adjuvant Keytruda were revealed. This regimen represents a breakthrough, as it marks the first instance where an immunotherapy-based treatment has shown a statistically significant improvement in overall survival (OS) compared to chemotherapy alone for patients with high-risk early-stage triple-negative breast cancer (TNBC). TNBC is linked to a shorter OS compared to other breast cancer subtypes, even with the use of curative-intent anthracycline- and taxane-based systemic chemotherapy. The risk of recurrence and mortality is elevated in patients with stage II or III TNBC, with a five-year event-free survival (EFS) rate of about 71% and an OS rate of roughly 77%, revealing a high unmet need in this patient population.

In 2021, the FDA criticised MSD for relying on an early endpoint to seek approval for Keytruda in early-stage TNBC. However, now the PD-1 inhibitor has robust OS data to strengthen its case. Out of the 1,174 patients who were randomized, 784 received Keytruda with chemotherapy, while 390 were given a placebo with chemotherapy. By the data cutoff on March 22, 2024, the median follow-up time was 75.1 months and 14.7% of patients in the Keytruda group had died, compared to 21.8% in the control group. The estimated five-year OS was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the Keytruda-chemotherapy group, compared to 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). The OS data further supports Keytruda's role as a perioperative therapy in early-stage TNBC, following its FDA approval in 2021. The approval was based on EFS data, which showed that the treatment reduced the risk of disease recurrence, progression, new cancer development, or death by 37% compared to chemotherapy alone in the neoadjuvant setting. Regarding safety, immune-mediated adverse events (AEs) and infusion reactions of any grade in the combined neoadjuvant and adjuvant phases occurred in 33.5% of patients in the Keytruda arm and 11.3% in the chemotherapy-placebo arm. The increase in AEs occurring in the Keytruda group could have a notable impact on its commercial uptake in TNBC. While Keytruda's efficacy data is strong, the higher rate of immune-related AEs could raise concerns among clinicians, especially in high-risk, early-stage TNBC patients where treatment tolerance is critical. However, given Keytruda’s demonstrated OS benefits, the commercial adoption is still likely to be strong, but patient management strategies around side effects will be crucial.

Keytruda's outstanding performance in the KEYNOTE-522 trial has set it apart from Roche's PD-L1 inhibitor, Tecentriq (atezolizumab). Roche faced setbacks with Tecentriq last year, having to put the Phase III IMpassion030 trial on halt following an interim analysis. This trial investigated the effectiveness of Tecentriq combined with chemotherapy as a postsurgical adjuvant therapy for TNBC. The interim results revealed that the Tecentriq-chemo combination did not offer the anticipated benefit. It was associated with a higher risk of recurrence or death compared to adjuvant chemotherapy alone. Nonetheless, the issue of immunotherapy resistance is highly relevant to breast cancer, particularly in aggressive subtypes like TNBC. Keytruda works by reinvigorating T cells to attack the tumour. Over time, continuous stimulation can lead to T-cell exhaustion, diminishing their ability to kill cancer cells. Exhausted T cells are less responsive to immunotherapy, limiting the long-term benefit of Keytruda if the tumour acquires resistance or recurs, curbing the drug’s effectiveness in the recurrent or metastatic setting. GlobalData’s consensus forecast projects global sales for Keytruda to reach $23.2bn by 2030, driven by increased uptake for already approved indications across markets and expansion into new indications.