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KEYNOTE-001

ASCO 2019: Pembrolizumab facilitates previously unmet 5-year-overall survival for NSCLC

The longest follow-up study to date of people with aNSCLC treated with pembrolizumab shows previously unmet 5-year-overall survival rates in patients with advanced non-small-cell lung cancer.

At this year’s ASCO Annual Meeting, the 5-year-follow-up of the Phase Ib KEYNOTE-001 basket trial (NCT01295827) was presented. KEYNOT-001 was the first study that investigated the anti-PD-1 antibody pembrolizumab in various solid tumors; this is the longest pembrolizumab follow-up to date.

KEYNOTE-001 enrolled 550 patients with advanced non-small-cell lung cancer (NSCLC), 101 of which had not received previous chemotherapy. All patients received pembrolizumab in a dosage of 2 mg/kg every 3 weeks, or 10 mg/kg every 2 or 3 weeks. In past years, the dosage was changed to a weight-independent fixed dose of 200 mg every three weeks, which has become established in clinical practice.

Pembrolizumab trial with the longest follow-up

After a median follow-up of 60.0 months, 18 percent of all participants were still alive. In the group of chemotherapy-naïve patients, the 5-year-overall survival rate was 23.3%; in the pre-treated group 15.5%. These data show a substantial improvement compared to the pre-immunotherapy era, in which average 5-year-OS rates were around 5%, according to data from the SEER registry.

»The uniformly negative outlook that has been associated with a diagnosis of advanced non-small-cell lung cancer is certainly no longer appropriate,” said lead study author Edward B. Garon, MD, MS, Associate Professor of Medicine at UCLA, Los Angeles, CA. »The fact that we have patients on this trial who 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.”

PD-L1 expression level critical

The highest clinical benefit was observed in non-pre-treated patients with high PD-L1 expression (50 percent of tumor cells positive, 5-year-OS: 29.6 percent), while patients with PD-L1 expression below 50% had a 5-year-OS of 15.7%. In pre-treated patients, 5-year-OS in the group with PD-L1>50%, 5-year-OS was 25%, in the group with PD-L1 1-49% 12.6%, and in the group <1% only 3.5%.

Responders generally had a long duration of response (DoR):  In the pretreated group, 42 percent responded, with a median DoR of 16.8 months, in the group that received pembrolizumab as first-line therapy, 23 percent responded for a median of 38.9 months.

Next steps

Dr. Garon noted that researches will try to decipher which patients have the highest benefit from pembrolizumab therapy. Furthermore, they will work to identify impediments that could prevent the antitumor immune response to guide development of possible combination therapies.

Garon EB et al.: Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001; ASCO 2019; Abstract LBA9015

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