Local experts expressed dissatisfaction with MSD’s Keynote-604 trial results on the effectiveness of adding Keytruda to chemotherapy as the first-line treatment of extensive-stage small-cell lung cancer (SCLC).
Such results will make it difficult for MSD to obtain regulatory approval for Keytruda, they said.
Cho Byung-chul, head of the Lung Cancer Center of Yonsei Cancer Center, appeared on “Medical Library,” a new YouTube channel for continuous medical education operated by The Korean Doctors’ Weekly, to review the American Society of Clinical Oncology 2020 meeting.
|Experts are reviewing the American Society of Clinical Oncology 2020 meeting for a YouTube show, “Medical Library,” which will be aired on July 11. From left are Yonsei Cancer Center’s Lung Cancer Center Professors Hong Min-hee, Lim Sun-min, Cho Byung-chul, Kim Hye-ryun, and Ahn Byeong-cheol.|
During the show, he reviewed the Keynote-604 trial with four other professors of the Lung Cancer Center – Kim Hye-ryun, Hong Min-hee, Lim Sun-min, and Ahn Byeong-cheol.
Explaining the study's background, Kim said drug companies have recently introduced immunotherapies in SCLC, just like they did so in other types of cancer.
In the first-line treatment of extensive-stage SCLC, PD-L1 inhibitors Tecentriq and Imfinzi, combined with etoposide plus cisplatin, showed superiority to chemotherapy alone, she said. The two drugs won FDA approval and are emerging as the new standard care, she added.
Keytruda, also a PD-L1 inhibitor, is challenging to obtain a regulatory nod as the third immunotherapy in SCLC.
The phase-3 Keynote-604 trial compared Keytruda plus standard chemotherapy (etoposide+cisplatin or etoposide+carboplatin) with the conventional standard chemotherapy in 453 patients with extensive-stage SCLC. The primary endpoints were set dual – progression-free survival (PFS) and overall survival (OS).
Kim said PFS at 12 months was 15.9 percent in the Keytruda combo group, versus 5 percent in the control arm. At 18 months, PFS in the Keytruda treatment group stood at 10.8 percent, versus 2.1 percent in the control group.
|The progression-free survival (PFS) and overall survival (OS) graphs in the Keynote-604 study on Keytruda.|
In terms of OS, the Keytruda combo group showed 45.1 percent in OS at 12 months, while the control group had 39.6 percent in OS. At 24 months, OS recorded 22.5 percent and 11.2 percent, respectively, showing that the Keytruda combo group’s OS was about two folds higher.
“Although the hazard ratio (HR) was 0.8, the study did not reach statistically meaningful results in terms of ‘p-value.’ So, this study has failed to reach the OS goal,” Kim said.
As the Keytruda combo group did not show survival benefits compared to the control group in extensive-stage SCLC, the researchers concluded that the trial did not meet the dual primary endpoints.
Cho said the study results were “very disappointing.”
Given Keytruda’s prominent role in SCLC compared to the other anti-PD-L1 immunotherapies such as Tecentriq or Imfinzi, the latest results were a significant defeat for Keytruda, he said.
Cho said MSD might not be able to earn the license from the FDA with this outcome alone because adding the PD-L1 inhibitor to the standard chemotherapy did not show an OS benefit. At the same time, the median PFS is only about 12 months now.
The Impower133 trial on Tecentriq was published in the New England Journal of Medicine, and the CASPIAN study on Imfinzi, in The Lancet, Cho said. “Both of them were the basis for the drug approval and reached the primary endpoints. But the Keynote-604 on Keytruda was published in the Journal of Clinical Oncology, and did not reach the OS, which will make it difficult to win approval,” he added.
The experts’ review on the latest Keytruda trial will be uploaded on the site of The Korean Doctors’ Weekly and its YouTube channel, Medical Library, on July 11.