Pre-emptive US check for Keytruda's latest US use
Fresh from restricting several gastric cancer approvals, including Keytruda's, to PD-L1 expressers, the FDA has acted pre-emptively when greenlighting the Merck & Co drug's new use for the perioperative treatment of head and neck cancer. Approval came on Thursday, 10 days before the PDUFA date, but the new indication is limited to patients whose tumours express PD-L1 at 1% or higher. This is in spite of Merck arguing at AACR that the supporting Keynote-689 study showed an all-comers benefit on event-free survival – a claim that was technically correct, but which benefited from PD-L1 expressers driving up the result across the entire dataset. It's still not disclosed how Keynote-689's PD-L1-negative patients did, but extrapolation suggests that any benefit here was marginal: hazard ratios for EFS worsened from 0.66 for the PD-L1 ≥10% group. to 0.70 for PD-L1 ≥1%, to 0.73 for all-comers. The US approval is Keytruda's fourth in head and neck cancer, with monotherapy having first and second-line labels (the former in the PD-L1 ≥1% population), and chemo combo also being approved front line. 11 US-approved uses across all indications are now limited to PD-L1 expressers.
US Keytruda approvals limited to PD-L1 expressers
| US approval | Trial | Regimen | Setting | Restriction |
|---|---|---|---|---|
| 12 Jun 2025 | Keynote-689 | ChemoRT+monotherapy | Neoadjuvant (+ adjuvant) head & neck cancer | PD-L1 ≥1% |
| 16 Nov 2023 | Keynote-859 | Chemo combo | 1st-line HER2-ve gastric/GEJ adenocarcinoma | PD-L1 ≥1% from Jun 2025 (originally all-comers) |
| 13 Oct 2021 | Keynote-826 | Chemo +/- Avastin combo | 1st-line cervical cancer | PD-L1 ≥1% |
| 5 May 2021 | Keynote-811 | Herceptin+chemo combo | 1st-line HER2+ve gastric/GEJ adenocarcinoma | PD-L1 ≥1% from Nov 2023 (originally all-comers) |
| 22 Mar 2021 | Keynote-590 | Chemo combo | 1st-line oesophageal/GEJ carcinoma | PD-L1 ≥1% from Jun 2025 (originally all-comers) |
| 13 Nov 2020 | Keynote-355 & 522 | Chemo combo | 1st-line triple-negative breast cancer | PD-L1 ≥10% |
| 30 Jul 2019 | Keynote-180 & 181 | Monotherapy | 2nd-line oesophageal squamous cell carcinoma | PD-L1 ≥10% |
| 10 Jun 2019 | Keynote-048 | Monotherapy | 1st-line squamous head & neck cancer | PD-L1 ≥1% |
| 11 Apr 2019 | Keynote-042 | Monotherapy | 1st-line (not candidates for chemoRT), ALK & EGFR-ve, NSCLC (incl stage III) | PD-L1 ≥1% |
| 12 Jun 2018 | Keynote-158 (cohort E) & 826 | Monotherapy | 2nd-line cervical cancer | PD-L1 ≥1% |
| 22 Sep 2017 | Keynote-059 | Monotherapy | 3nd-line gastric/GEJ adenocarcinoma | PD-L1 ≥1% (later withdrawn after negative adcom vote) |
| 24 Oct 2016 | Keynote-024 | Monotherapy | 1st-line NSCLC | PD-L1 ≥50% (later expanded to ≥1%) |
| 24 Oct 2016 | Keynote-010 | Monotherapy | 2nd-line NSCLC | PD-L1 ≥1% |
| 2 Oct 2015 | Keynote-001, 024 & 010 | Monotherapy | 2nd-line NSCLC | PD-L1 ≥50% (later expanded to ≥1%) |
Source: OncologyPipeline.
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