Pembrolizumab quadrupled pre-immunotherapy era 5-year survival rates for patients when used as initial therapy (23.2% vs 5.5 %). For patients who received prior therapies, pembrolizumab increased survival rates to 15.5%. Across both patient populations studied, 5-year survival rates were highest among those whose tumours had PD-L1 expression of 50% or more vs 1-49% (as initial therapy arm: 29.6% vs 15.7%; prior therapy arm: 25% vs 12.6%) .
Five-year data from the phase 1b KEYNOTE-001 clinical trial show that pembrolizumab was safe and effective and substantially increased overall survival for advanced non-small cell lung cancer (aNSCLC). Specifically, 23.2% of people who had not previously been treated with chemotherapy and 15.5% of previously treated patients were alive after 5 years, with the greatest benefit observed in patients with higher PD-L1 expression. This represents a marked improvement over 5-year survival rates from the pre-immunotherapy era, which averaged 5.5% for aNSCLC. This is the longest follow-up study to date of people with aNSCLC treated with pembrolizumab, according to the researchers.
“The uniformly negative outlook that has been associated with a diagnosis of aNSCLC is certainly no longer appropriate,” said lead study author Prof. Edward Garon (UCLA, Los Angeles, USA). “The fact that we have patients on this trial that are still alive after 7 years is quite remarkable. We also have evidence that most patients who are doing well after 2 years on pembrolizumab live for 5 years or more.” Pembrolizumab is a PD-1 inhibitor, and is approved as a first-line treatment for aNSCLC tumours that do not have EGFR or ALK gene mutations but that express PD-L1 on 50% or more of their cells.
There were 550 people with aNSCLC in the trial, including 101 patients who had not previously received any treatment and 449 patients who had received prior treatment. All patients received 2 mg/kg of their body weight of pembrolizumab every 3 weeks or 10 mg/kg every 2 or 3 weeks. In recent years, however, the protocol was changed to a single dose of 200 mg regardless of body weight every 3 weeks, the typical regimen in clinical practice.
Patients were followed for a median of 60.6 months, or about 5 years. At that point, 18% of enrolees (100 participants) were still alive. Of those who had not received prior treatment, 23% were still alive after 5 years compared with 15.5% of those previously treated. Researchers observed that higher levels of PD-L1 expression predicted longest survival. Specifically:
• In previously untreated people, 29.6% with PD-L1 expression of 50% or more were alive after 5 years compared with 15.7% with expression levels below 50%.
• In people who had been previously treated, 25% who had PD-L1 expression levels of 50% or more were alive after 5 years compared with 12.6% with expression levels between 1 to 49%. Only 3.5% of people with expression levels below 1% were alive after 5 years.
Among people receiving pembrolizumab after undergoing previous treatment, 42% had responses that lasted for a median of 16.8 months. For those who received pembrolizumab as initial therapy, 23% had responses that lasted a median of 38.9 months. Immune-related toxic side effects occurred in 17% of enrolees. The most common side effect was hypothyroidism; the most serious side effect were a few rare cases of pneumonitis.
- Garon E. et al. Abstract LBA9015. Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001. ASCO 2019, 31 May-4 June, Chicago, USA.