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Keytruda boosts event-free survival by up to 39% in early triple-negative breast cancer

In patients with early triple-negative breast cancer, pembrolizumab (Keytruda) with chemotherapy cuts recurrence by up to 39%, found a three-year follow-up of the Keynote-522 trial, in the New England Journal of Medicine.

The drug works by helping the immune system recognise and attack cancer cells, and is already used to treat lung cancer, skin cancer, bladder cancer and Hodgkin lymphoma. It is administered, with the number of sessions depending on the type of cancer.

UK researchers have found that if given in combination with chemotherapy before surgery, and then again on its own after surgery, it can stop the return of the disease in women with triple-negative breast cancer, an aggressive type of the disease.

In the Keynote-522 trial, women with early triple-negative breast cancer, where the disease had not yet spread beyond the breast and lymph nodes (stages two and three), were treated with Keytruda in addition to standard chemotherapy, before surgery, followed by Keytruda after surgery.

After a follow-up period of more than three years, experts led by Queen Mary University of London and Barts Health NHS trust found the risk of disease recurrence was 37% lower in patients treated with the drug combination than in those treated with chemotherapy alone.

“We had previously demonstrated that the addition of immunotherapy to pre-operative chemotherapy increases the treatment response in patients with triple-negative breast cancer at the time of surgery,” said study lead Prof Peter Schmid, of Queen Mary and St Bartholomewʼs Hospital. “We now have long-term results demonstrating that the combination therapy significantly reduces recurrences by approximately 37%, including reduction of secondary breast cancer by 39%.

“This means that the cure rate for these cancers is significantly increased. The estimates are that – just in the US, where this treatment was recently approved by the Food and Drug Administration (FDA) – this new treatment may save as many as 10,000 lives per year.”

A total of 1,174 patients across 21 countries with previously untreated stage two or three triple-negative breast cancer were recruited for the trial, which was funded by the pharmaceutical company Merck Sharp & Dohme.

The current standard of care for patients with early-stage triple-negative breast cancer is chemotherapy, typically used to shrink the tumour before surgery. More than 8,000 women in the UK are diagnosed with this form of breast cancer every year.

“The risk of triple-negative breast cancer returning and spreading to other parts of the body in the first few years after treatment is higher than it is for other breast cancers,” said Dr Kotryna Temcinaite, of the charity Breast Cancer Now.


Study details

Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer

Peter Schmid, Javier Cortes, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, et al.

Published in the New England Journal of Medicine on 10 February 2022


The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported.

We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin–cyclophosphamide or epirubicin–cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab–chemotherapy group) or placebo (placebo–chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomisation to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed.

Of the 1174 patients who underwent randomisation, 784 were assigned to the pembrolizumab–chemotherapy group and 390 to the placebo–chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab–chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo–chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone.


NEJM abstract – Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer (Open access)


See more from MedicalBrief archives:


Improved response from triple negative breast cancer patients to immune plus chemotherapy


Immunotherapy plus chemo increases breast cancer survival rates


Keytruda approved in SA for bladder cancer and non-small cell lung carcinoma


‘Potential new standard’ in high-risk kidney cancer — KEYNOTE-564 trial


Merck's kidney cancer therapy approved ahead of expectations



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