KEYNOTE-522: final OS findings of pembrolizumab and chemotherapy in TNBC

Summary

The KEYNOTE-522 trial investigated the combination of chemotherapy and the immune checkpoint inhibitor, pembrolizumab (pemb), in patients with stage II and III triple-negative breast cancer (TNBC). Results from the trial, including 5-year follow-up data, showed significant improvements in event-free survival (EFS) and overall survival (OS) for patients receiving the combination treatment. A reduction in recurrence risk by 35% and a 34% reduction in the risk of death were observed. Additionally, there were no new safety concerns, reinforcing the safety profile of the treatment. These findings highlight the potential benefits of combining chemotherapy with immune checkpoint inhibition in TNBC patients.

Takeaways

• 😀 The KEYNOTE 522 trial tested preemptive chemotherapy combined with the immune checkpoint inhibitor, pembrolizumab (pembro), followed by surgery and additional pembro treatment for 6 months.
• 😀 The trial focused on stage 2 and stage 3 triple-negative breast cancer (TNBC) patients, randomizing them to either chemotherapy with pembro or chemotherapy with placebo.
• 😀 The chemotherapy regimen included 12 weeks of weekly nab-paclitaxel and carboplatin, followed by AC or EC for another 12 weeks.
• 😀 The primary endpoints were pathological complete response (pCR) and event-free survival (EFS). Initial results showed a significant 30.6% increase in pCR rates to just under 65%.
• 😀 After three years of follow-up, the trial showed a significant reduction in recurrences with a hazard ratio (HR) of 0.65, which persisted even after five years.
• 😀 Event-free survival curves plateaued between years 3-5, with a stable hazard ratio of 0.65, reflecting the effectiveness of the treatment over time.
• 😀 At 5 years, the absolute event-free survival rates were 81% for patients treated with chemotherapy and pembro, and 72% for those who received chemotherapy alone.
• 😀 The overall survival (OS) data showed a significant 34% reduction in the risk of death (HR 0.66) at 25 months of follow-up, demonstrating the treatment's long-term benefit.
• 😀 Subgroup analyses indicated consistent OS benefits across all patient groups, including those categorized by PD-L1 status, tumor size, and lymph node involvement.
• 😀 A pre-planned analysis comparing patients with optimal response (pCR) vs. residual disease showed a better overall survival for those treated with chemotherapy and immune therapy, with a 6% absolute survival difference.

Q & A

What was the purpose of the K 522 trial?

The K 522 trial aimed to evaluate the effectiveness of preemptive chemotherapy in combination with the immune checkpoint inhibitor, PMIS, followed by surgery and further PMIS treatment for another 6 months in patients with stage 2 or 3 triple-negative breast cancer.

What were the primary endpoints of the K 522 trial?

The trial had two primary endpoints: the short-term endpoint, which was pathological complete response (pathCR), and the long-term endpoint, which was event-free survival and overall survival.

What chemotherapy regimen was used in the K 522 trial?

The chemotherapy regimen used was a combination of 12 weeks of weekly paclitaxel-carboplatin followed by 12 weeks of AC or EC chemotherapy.

What was the result of the first primary endpoint, pathCR, in the K 522 trial?

The trial demonstrated a significant increase in pathCR rates by about 30.6%, achieving just under 65% in patients treated with chemotherapy and PMIS.

What did the 3-year follow-up data from the K 522 trial show?

The 3-year follow-up data showed a significant reduction in recurrences with a hazard ratio of 0.65, indicating a 35% reduction in recurrence risk.

How did the 5-year data compare to the 3-year results in the K 522 trial?

At 5 years, the recurrence curves began to plateau, and the hazard ratio remained stable at 0.65, with around 90-95% of recurrences occurring within the first 5 years in triple-negative breast cancer patients.

What were the event-free survival rates at the 5-year follow-up in the K 522 trial?

The 5-year event-free survival rates were approximately 81% for patients treated with chemotherapy and PMIS, and about 72% for those receiving chemotherapy alone.

What new data was presented at the 75-month follow-up of the K 522 trial?

At the 75-month follow-up, a significant improvement in overall survival was observed, with a hazard ratio of 0.66, representing a 34% reduction in the risk of death.

How did the combination of chemotherapy and PMIS compare to chemotherapy alone in terms of overall survival?

The combination of chemotherapy and PMIS showed a significantly better overall survival rate compared to chemotherapy alone, with a 34% reduction in the risk of death, and the benefit was consistent across all patient subgroups.

What safety findings were reported in the K 522 trial after long-term follow-up?

No new long-term safety signals were observed in the K 522 trial. The safety data remained consistent with what was previously reported for chemotherapy and immune therapy combinations.