Yago Garitaonaindía, Translational Research Fellow at CCIT-DK – National Center for Cancer Immune Therapy of Denmark, shared on LinkedIn:
“KEYNOTE-867 is out in JCO: adding pembrolizumab to SBRT in unresected stage I-II NSCLC did not improve EFS and added toxicity.
Prof. Andreas Pirche
Phase 3, double-blind, 448 patients (median age 73, 82% medically inoperable) randomized to SBRT plus pembrolizumab or placebo. The trial stopped early at the first interim analysis, with a median follow-up of 20.6 months.
Results
- Median EFS 31.2 vs 28.3 months | HR 0.92 (0.69-1.24),
- OS HR 1.33 (0.93-1.90), numerically worse in the IO arm,
- Grade 3-5 treatment-related AEs: 20.4% vs 3.7%,
- 5 treatment-related deaths, all in the pembrolizumab arm,
- There was a signal toward benefit in the under-65 group (EFS HR 0.48, CI 0.18-1.24), but it rests on 66 patients and 20 events and should be taken very cautiously. The trial was not designed to test it.
Some takes
Concurrent RT + IO doesn’t seem to translate into clinical benefit: PACIFIC-2 found no benefit in stage III, and now this. Nodal irradiation, a possible explanation for PACIFIC-2, does not apply here (N0, SBRT to the primary only).
It contradicts the randomized phase 2 of SBRT with nivolumab (I-SABR), which was open-label, smaller, gave a shorter course of IO and had more tumors of 2 cm or less (61% vs 39%).
Sequencing may matter: sequential durvalumab after SBRT improved time to progression in the randomized phase 2 ASTEROID, but DFS and OS were flat.
Open question: induction chemo-IO before radiotherapy (APOLO and PACIFIC-Brazil are single-arm phase 2 in stage III). S1914, with atezolizumab before and after SBRT, was negative (OS HR 1.04). Could chemo-IO work here?”
Title: KEYNOTE-867: A Phase III, Randomized, Double-Blind Study of Stereotactic Body Radiotherapy With Pembrolizumab for Unresected Stage I or II Non–Small Cell Lung Cancer.
Authors: Salma K. Jabbour, Szabolcs Sótér, Michael Eaton, Gabriella Gálffy, Dariusz Kowalski, Akito Hata, Augusto Valdivia, Nikolaj Frost, Evgeny Levchenko, Mariana Monteiro, Anoop Haridass, Myriam Bouchard, Ki Hyeong Lee, Myung-Ju Ahn, Brett G.M. Hughes, André Durham, Yan Xu, Ayman Samkari, Andrew Song, Andreas Pircher.
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