KEY TAKEAWAYS
- Phase 2 trial (KEYNOTE-799) evaluated the efficacy and safety of pembrolizumab plus (cCRT) in patients with previously untreated, unresectable, locally advanced stage III NSCLC.
- The primary aim was to assess the ORR and the incidence of grade ≥3 pneumonitides in two cohorts of patients.
- Patients in cohort A received carboplatin, paclitaxel, and pembrolizumab, followed by additional cycles of pembrolizumab plus standard TRT.
- The median duration of response and overall survival was not reached in both cohorts, and median progression-free survival was 30.6 months in cohort A and not reached in cohort B.
- Pembrolizumab plus cCRT showed consistent efficacy across PD-L1 expression levels and histology subtypes, and grade ≥3 pneumonitides occurred in 7.5% of patients overall.
Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC showed that pembrolizumab (pembro; anti-PD-1) plus cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; nonsquamous only) and grade ≥3 pneumonitides in 9 (8.0%) and 7 (6.9%) pts, respectively. With an additional year of observation, researchers present revised findings. Participants in this phase 2 non-randomized study had to be 18 or older and have stage IIIA-C NSCLC with the measurable disease according to RECIST v1.1. Cohort A patients (squamous and nonsquamous) received carboplatin AUC 6 plus paclitaxel 200 mg/m2 and pembro 200 mg for one 3-week cycle, then carboplatin AUC 2 plus paclitaxel 45 mg/m2 QW for 6 wks, plus 2 cycles of pembro 200 mg Q3W, plus standard thoracic radiotherapy (TRT). Cohort B (nonsquamous) patients were treated with cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and pembro 200 mg Q3W, in addition to standard TRT in cycles 2 and 3. Patients continued to receive pembro 200 mg Q3W for a total of 14 cycles. Outcomes of interest included the rate of pneumonitis of grade 3 or higher and overall response rate (ORR) as measured by RECIST v1.1 by blinded independent central review (BICR) (per NCI CTCAE v4.0).
There were 216 patients enrolled in the study, 112 of whom were treated (102 in Cohort A and 100 in Cohort B). The median (range) time from the first dose to database cutoff (Oct 18, 2021) was 30.2 (25.3–35.5) mo in cohort A and 25.4 (14.5–35.2) mo in cohort B. The ORR (95% CI) for Cohort A was 71.4% (62.1%-79.6%), while Cohort B’s was 75.5% (66.0%-83.5%). Both cohorts had median progression-free survival (PFS) of 30.6 months (cohort A) and NR (cohort B). Patients in cohort A with PD-L1 TPS <1% had an ORR of 66.7%, while patients in cohort B with PD-L1 TPS ≥1% had an ORR of 77.3%. The ORR for squamous and nonsquamous cancers was 72.0% and 74.1 %, respectively. Overall, 16 patients (7.5%) were diagnosed with grade 3 pneumonitis, with 9 patients (8.0%) in cohort A and 7 patients (6.7%) in cohort B. Cohort A saw 64.3% of patients experiencing treatment-related grade≥ 3 AEs, while cohort B saw 51.0%. Patients with untreated locally advanced stage III NSCLC continue to show robust and durable responses after receiving >2 y of follow-up plus cCRT, regardless of PD-L1 TPS and tumor histology, with a promising survival outcome and manageable safety.
Source: https://meetings.asco.org/abstracts-presentations/207962
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03631784
Martin Reck, Ki Hyeong Lee, Nicolaj Frost, Valeriy Vladimirovich Breder, Dariusz Kowalski, Evgeny Levchenko, Noemi Reguart, Alex Martinez-Marti, Baerin Houghton, Jean-Baptiste Paoli, Sufiia Safina, Takefumi Komiya, Amy Sanford, Hong Liu, Andrew J. Song, Steven M. Keller, Salma K. Jabbour/Two-year update from KEYNOTE-799: Pembrolizumab plus concurrent chemoradiation therapy (cCRT) for unresectable, locally advanced, stage III NSCLC/J Clin Oncol 40, 2022 (suppl 16; abstr 8508)DOI10.1200/JCO.2022.40.16_suppl.8508
