KEY TAKEAWAYS
- KEYNOTE-412 is a randomized, double-blind, phase 3 clinical trial for pembro + CRT compared to placebo + CRT in patients with LA-HNSCC.
- The primary endpoint of the study was EFS ( P=0.0242).
- About 804 pts were randomized, with baseline characteristics well balanced between arms.
- At the data cutoff, there was a favorable trend towards improved EFS with adding pembro vs. placebo to CRT (HR 0.83, P=0.0429).
- Treatment-related AEs led to death in 1.0% vs. 1.5% of pts in the pembro and placebo arms, respectively.
- Pembro is approved as monotherapy or in combination with chemotherapy for recurrent/metastatic HNSCC.
In recurrent or metastatic HNSCC, Pembro can be used alone or with chemotherapy. The KEYNOTE-412 (NCT03040999) study compared the efficacy and safety of pembro Plus CRT with placebo + CRT in patients (pts) with LA-HNSCC in a randomized, double-blind, phase 3 trial.
Pts with newly diagnosed, pathologically proven, treatment-naive LA-HNSCC (T3-T4 [N0-N3] or any N2a-3 [T1-T4] larynx/hypopharynx/oral cavity/p16-negative oropharynx cancers and T4 or N3 p16-positive oropharynx cancer) who were eligible for definitive CRT were randomized (1:1) to pembro 200 mg Q3W + CRT (70Gy/35F + cisplatin 100 mg/m2 Q3W) followed by pembro or placebo Q3W + CRT followed by placebo. Seventeen doses were administered: a priming dose of pembro/placebo one week before CRT, two doses during CRT, and 14 doses of maintenance therapy after CRT. The primary efficacy objective was extended follow-up time (EFS; efficacy boundary, one-sided P=0.0242). Secondary outcomes included OS and safety/tolerability.
A total of 804 points were assigned at random (402 pts in each arm). Overall, baseline characteristics were fairly distributed across the two groups. The median period from randomization to data cutoff (May 31, 2022) for the final analysis was 47.7 (range, 37.0-61.4) months. Pembro added to CRT had a trend towards improving EFS compared to placebo (HR 0.83, P=0.0429; Table), but the difference was not statistically significant. Discontinuation of cisplatin, RT, and/or pembro/placebo occurred in 41.2% vs. 33.2% of patients in the pembro arm and 1.0% vs. 1.5% of patients in the placebo arm due to treatment-related adverse events.
Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/primary-results-of-the-phase-iii-keynote-412-study-pembrolizumab-pembro-with-chemoradiation-therapy-crt-vs-placebo-plus-crt-for-locally-advanc
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03040999
Primary results of phase III KEYNOTE-412 study: Pembrolizumab (pembro) with chemoradiation therapy (CRT) vs placebo plus CRT for locally advanc… | OncologyPRO. (n.d.). Oncologypro.esmo.org. Retrieved March 24, 2023, from https://oncologypro.esmo.org/meeting-resources/esmo-congress/primary-results-of-the-phase-iii-keynote-412-study-pembrolizumab-pembro-with-chemoradiation-therapy-crt-vs-placebo-plus-crt-for-locally-advanc
