The October 2024 issue of ASCO Post features groundbreaking results from the phase III KEYNOTE-671 trial. This trial explored the impact of using pembrolizumab, an immunotherapy drug, during the perioperative period in patients diagnosed with resectable non-small cell lung cancer (NSCLC). The findings have significant implications for the treatment of early-stage lung cancer.
Overall Survival Benefit: A Promising Outcome
The KEYNOTE-671 trial revealed a substantial increase in overall survival for patients who received pembrolizumab alongside standard chemotherapy. This combination therapy, administered both before and after surgery, demonstrated a clear advantage over chemotherapy alone.
Specifically, at the second interim analysis, the data showed a compelling difference in survival rates. The group who received pembrolizumab achieved a 71% overall survival rate after 36 months. In contrast, the control group, who received only chemotherapy, had a 64% survival rate. This difference translates to a hazard ratio (HR) of 0.72 (P = .0052), highlighting the significant positive impact of pembrolizumab on survival.
Enhanced Event-Free Survival: Extending Time Without Disease Progression
The trial also demonstrated that incorporating perioperative pembrolizumab led to a remarkable improvement in event-free survival. This means patients lived longer without experiencing a return of their cancer or other disease-related complications.
The median event-free survival was dramatically different between the two groups. Patients in the pembrolizumab group lived a median of 47.2 months without their disease progressing. This starkly contrasted with the placebo group, who only achieved a median event-free survival of 18.3 months. This substantial improvement is reflected in the HR of 0.59 (95% CI = 0.48–0.72), underscoring the effectiveness of pembrolizumab in delaying disease recurrence.
Safety and Tolerability: Balancing Benefits with Potential Risks
While the efficacy results of KEYNOTE-671 are encouraging, understanding the safety profile of any new treatment is crucial. In this trial, the addition of pembrolizumab did lead to a slightly higher occurrence of side effects, but these were generally manageable and did not outweigh the survival benefits.
Grade ≥ 3 treatment-related adverse events, which are considered severe, were reported in 45% of patients who received pembrolizumab. In the control group, this rate was 38%. Notably, immune-related adverse events, a known potential side effect of immunotherapy, were also higher in the pembrolizumab group, affecting 7% of patients compared to 2% in the control group.
Importantly, while there were some instances of death related to treatment, the rates were very low and comparable between the two groups. Four patients (1%) in the pembrolizumab group and three patients (1%) in the control group experienced fatal treatment-related adverse events.
Understanding the KEYNOTE-671 Trial Design
The KEYNOTE-671 trial, conducted globally, adhered to a rigorous double-blind design, ensuring that neither the participants nor the researchers were aware of who received pembrolizumab or the placebo. This rigorous approach strengthens the reliability of the trial’s findings.
Between May 2018 and December 2021, 797 patients with resectable NSCLC were enrolled in the trial. They were randomly assigned to either the pembrolizumab group (n = 397) or the control group (n = 400), ensuring a balanced distribution of patient characteristics between the groups.
The treatment regimen for the pembrolizumab group consisted of four cycles of neoadjuvant pembrolizumab at a dose of 200 mg every three weeks. This was administered alongside standard cisplatin-based chemotherapy. After surgery, patients received an additional thirteen cycles of adjuvant pembrolizumab at the same dose and schedule. The control group received a placebo instead of pembrolizumab throughout the study.
Conclusion: New Hope for Resectable NSCLC Patients
The KEYNOTE-671 trial offers a beacon of hope for patients diagnosed with resectable, early-stage NSCLC. The results conclusively demonstrate that the addition of perioperative pembrolizumab to standard chemotherapy significantly improves overall survival and extends the time patients live free from disease progression. While there is a slight increase in treatment-related side effects, these are generally manageable and do not overshadow the substantial clinical benefits.
This landmark trial provides strong evidence to support the use of perioperative pembrolizumab as a new standard of care for this patient population. By integrating this immunotherapy approach into treatment plans, clinicians can offer their patients a greater chance of long-term survival and an improved quality of life.
Frequently Asked Questions About KEYNOTE-671 and Pembrolizumab for NSCLC
What is NSCLC, and why is this trial significant?
NSCLC is a common type of lung cancer. This trial is groundbreaking because it shows that adding pembrolizumab to chemotherapy before and after surgery helps patients live longer and reduces the risk of cancer returning.
What is perioperative pembrolizumab, and how does it work?
Perioperative means the time before and after surgery. Pembrolizumab is an immunotherapy drug. It helps the body’s immune system recognize and attack cancer cells more effectively.
What were the main side effects in the trial?
Both groups experienced side effects, but those receiving pembrolizumab had slightly more. These included fatigue, nausea, and skin reactions. Serious side effects were manageable and rare.
Who is eligible for this treatment approach?
The trial focused on patients with resectable NSCLC, meaning their tumors could be surgically removed. Your doctor can determine if this treatment strategy is appropriate for your specific situation.
What does this mean for the future of NSCLC treatment?
This trial could change how doctors treat early-stage NSCLC. It highlights the benefits of immunotherapy in combination with standard treatment for potentially better outcomes.
Source: ASCO Post, October 2024