First-line treatment with Keytruda (pembrolizumab) continues to promote significant survival benefits and durable responses in people with metastatic non-small cell lung cancer (NSCLC) and high levels of PD-L1, compared with standard chemotherapy, according to five-year data from the KEYNOTE-024 Phase 3 clinical trial.
The results showed that twice as many Keytruda-treated patients were alive at five years, and that these individuals lived two times longer than those on chemotherapy.
Keytruda is currently approved as a first-line treatment for advanced NSCLC patients whose tumors have no mutations in the EGFR or ALK genes and are PD-L1 positive (low to high levels in the U.S. and high levels only in Europe).
“Before 2014, the five-year survival rate for patients in the U.S. with advanced non-small cell lung cancer was only 5%,” Martin Reck, MD, PhD, of the German Center of Lung Research and Lung Clinic Grosshansdorf, in Germany, said in a press release.
“KEYNOTE-024 showed that 31.9% of patients treated with Keytruda were alive at five years. Survival outcomes in these patients with metastatic lung cancer did not seem possible to many oncologists, including myself, several years ago,” added Reck, who has been involved in the several analyses of the trial’s data over the years.
In addition, more than 80% of patients who completed two years of Keytruda treatment “were alive and nearly half of these patients remained treatment-free, representing an encouraging new precedent in the first-line metastatic non-small cell lung cancer setting,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, and chief medical officer at Merck Research Laboratories. Merck (known as MSD outside North America) is the developer of Keytruda.
The findings, “KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%,” were presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020, held online Sept. 19-21.
An immune checkpoint inhibitor, Keytruda works by preventing an immune evasion mechanism involving the interaction between PD-L1 in cancer cells and the PD-1 receptor in T-cells, immune cells involved in the fight against cancer. Tumors with high levels of PD-L1 (more than 50% of cells producing PD-L1) tend to respond better to Keytruda.
Initiated in 2014, KEYNOTE-024 (NCT02142738) was designed to evaluate the safety and effectiveness of Keytruda, compared with standard platinum-based chemotherapy, in people with previously untreated advanced NSCLC, whose tumors had high PD-L1 levels and no EGFR or ALK mutations.
A total of 305 participants were randomly assigned to receive either 200 mg of Keytruda every three weeks (154 patients) or an investigator’s choice of standard chemotherapy (151 patients).
Patients received Keytruda for two years or until disease progression; those who progressed after that timeframe were able to undergo a second course of Keytruda treatment. Crossover from chemotherapy to Keytruda was allowed after disease progression.
A 2016 interim analysis — at about one year of follow-up — showed that Keytruda lowered the risk of disease progression or death by 50%, and the risk of death by 40%, compared with chemotherapy. In addition, the immune checkpoint inhibitor was associated with fewer adverse events than chemo.
At a median follow up of about two years, first-line treatment with Keytruda continued to be superior to chemotherapy at delaying disease progression and extending survival, despite 54% of patients in the chemotherapy group crossing over to the immune checkpoint inhibitor therapy.
Newly presented five-year data showed that nearly twice as many patients on Keytruda were alive, compared with those who received chemotherapy (31.9% vs. 16.3%). Keytruda-treated patients also lived twice as long (26.3 months vs. 13.4 months) and a median of two months longer without disease progression (7.7 vs. 5.5 months), compared with those on chemo.
Overall, Keytruda reduced the risk of disease progression or death by 50% and the risk of death by 38%, compared with chemotherapy. These survival benefits were observed despite 99 (66%) patients in the chemotherapy group crossing over to Keytruda.
A greater proportion of patients receiving Keyruda responded to treatment (46.1% vs. 31.1% in the chemo group) and the therapy resulted in durable, longer responses (29.1 months vs. 6.3 months in the chemotherapy group).
Notably, more than 80% of the 39 patients (25%) who completed two years of Keytruda responded to treatment (82%) and were alive (81.4%) at five years, and nearly half (46%) remained treatment-free. This suggested that completing two years of this therapy provided a long-term survival benefit.
A total of 12 patients received a second course of treatment.
No new treatment-associated safety concerns were identified, and a lower proportion of Keytruda-treated patients (31.2%) reported severe to life-threatening or fatal adverse events, compared with those receiving chemotherapy (53.3%). This type of adverse events occurred in 15.4% of patients completing the two-year Keytruda treatment.
These KEYNOTE-024 findings represent the longest follow-up, and first-ever five-year survival data, for an immunotherapy in a randomized Phase 3 trial evaluating a first-line treatment of NSCLC.
“The long-term survival benefit achieved with Keytruda as a single agent in this study is a great example of the progress we have made in lung cancer to provide patients with more time without disease progression and a chance at a longer life,” Reck said.
“Keytruda has become foundational in the treatment of metastatic lung cancer based on the sustained, long-term survival benefit demonstrated in our clinical trials. These new, first-of-their-kind five-year survival results from KEYNOTE-024 add to our understanding of the important role that Keytruda now has in the treatment of lung cancer,” Baynes added.
“We are grateful to the many patients and health care providers in this trial and our other trials for their essential role in these studies and in advancing cancer care,” Baynes said.
