KEYNOTE-522: What the Breast Cancer Trial Found

One trial, two primary endpoints, two papers

KEYNOTE-522 set two questions in advance and agreed to answer both.

The first was whether adding pembrolizumab to chemotherapy before surgery would leave more women with no cancer at all in the tissue removed. That answer came in 2020. The second was whether it would keep the cancer from returning. That took until 2022, because you cannot know whether something comes back until enough time has passed.

Reading only the first paper gives a partial picture. Reading only the second skips the reason the trial was designed the way it was.

Who took part, and what they received

Field	Detail
Trial	KEYNOTE-522
Identifier	NCT03036488
Phase	Phase 3
Design	Randomised 2:1, double-blind, placebo-controlled
Cancer type	Previously untreated stage II or III triple-negative breast cancer
Comparator	Pembrolizumab or placebo, added to the same chemotherapy before and after surgery
Primary endpoints	Pathological complete response and event-free survival

1,174 people were randomised: 784 to pembrolizumab with chemotherapy and 390 to placebo with chemotherapy.

Before surgery, everyone had four cycles of paclitaxel and carboplatin, then four cycles of an anthracycline with cyclophosphamide, with pembrolizumab or placebo alongside throughout. After surgery, pembrolizumab or placebo continued alone for up to nine more cycles.

The pathological complete response result

A pathological complete response means no invasive cancer left in the breast and no cancer in the lymph nodes when the surgical specimen is examined.

Among the first 602 people randomised, 64.8% of the pembrolizumab group reached it (95% CI 59.9 to 69.5) against 51.2% on placebo (95% CI 44.1 to 58.3). The difference was 13.6 percentage points (95% CI 5.4 to 21.8, p<0.001).

The event-free survival result, two years later

The 2022 report came at a median follow-up of 39.1 months, at the fourth planned interim analysis. An event meant disease progression that prevented surgery, a local or distant recurrence, a second primary cancer, or death from any cause.

At 36 months, 84.5% of the pembrolizumab group were event-free (95% CI 81.7 to 86.9) against 76.8% on placebo (95% CI 72.2 to 80.7). The hazard ratio was 0.63 (95% CI 0.48 to 0.82, p<0.001).

Put another way, roughly eight in ten women were free of any such event at three years on pembrolizumab, against roughly three-quarters on placebo. The gap is about seven and a half percentage points, in a subtype with a reputation for early recurrence.

What the treatment costs

Severe side effects — grade 3 or higher, and treatment-related — occurred across all phases in 78.0% of the pembrolizumab group and 73.0% of the placebo group.

Both numbers are high, and the chemotherapy backbone accounts for most of that. Treatment-related deaths occurred in 3 people on pembrolizumab (0.4%) and 1 on placebo (0.3%). Side effects were concentrated in the pre-surgery phase, when the chemotherapy was running.

What this does not mean

• It does not apply to stage I disease. Only stage II and III were eligible.
• It does not tell you whether the drug is needed after surgery if the specimen was already clear. Everyone continued regardless of what the pathology showed.
• It does not report overall survival. Event-free survival counts recurrences and deaths together.
• The first paper's recurrence data were immature. The durable result is the 2022 one, and it too is an interim analysis.

Questions at a triple-negative diagnosis

• Am I stage II or III, and does that match this trial?
• What does a pathological complete response change about what comes next?
• Which of these side effects belong to the chemotherapy, and which to the immune drug?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NEJM: Pembrolizumab for Early Triple-Negative Breast Cancer (KEYNOTE-522) (primary)
• NEJM: Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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