Salma K Jabbour, MD from Rutgers Cancer Institute of New Jersey/RWJBarnabas Health speaks about ASCO 2021 Abstract KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.
Link to Abstract:
https://meetings.asco.org/abstracts-presentations/196541
Background information:
The anti-PD-1 antibody pembrolizumab (pembro) combined concurrent chemoradiation treatment (cCRT) in patients with unresectable, locally advanced stage III NSCLC is being studied in KEYNOTE-799 (NCT03631784). Prior findings in a subgroup of patients (primary efficacy population) indicated an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5 percent in cohort B (nonsquamous, n = 61), with grade 3 pneumonitis in 8.0 percent and 7.9% of patients, respectively. The outcomes for all pts enrolled in KEYNOTE-799 are shown below.
Methodologies:
Patients aged 18 years old with previously untreated, unresectable, pathologically proven stage IIIAC NSCLC with detectable disease by RECIST v1.1 were included in this nonrandomized, multisite, open-label phase 2 study. Cohort A (squamous and nonsquamous) patients were given a single cycle of carboplatin AUC 6, paclitaxel 200 mg/m2, and pembro 200 mg. Pts were given carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 weeks, followed by 2 cycles of pembro 200 mg Q3W and routine thoracic irradiation (TRT). In cohort B (nonsquamous exclusively), patients were given three cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and pembro 200 mg Q3W, as well as TRT in cycles 2 and 3. All patients were given 14 further cycles of pembro 200 mg Q3W. ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade 3 pneumonitis were the primary objectives (per NCI CTCAE v4.0). All patients were evaluated for efficacy and safety as-is.
The following are the outcomes:
KEYNOTE-799 included 216 patients (cohort A, 112; cohort B, 104), with 112 in cohort A and 102 in cohort B receiving therapy. The median (range) period from the first dose to database cutoff in cohort A was 18.5 (13.6–23.8) months and 13.7 (2.9–23.5) months as of October 28, 2020. In cohort A, the ORR (95 percent CI) was 70.5 percent (61.2 percent 78.8%) while in cohort B, it was 70.6 percent (60.7 percent 79.2 percent). In neither cohort, the median DOR was met (Table). ORR was comparable independent of PD-L1 status ([TPS 1% and TPS 1% ]; Cohort A, 66.7 percent and 75.8% ; Cohort B, 71.4 percent and 72.5 percent ) or tumor histology ([TPS 1% and TPS 1% ]; Cohort A, 66.7 percent and 75.8% ; Cohort B, 71.4 percent and 72.5 percent ). (Cohort A, squamous, 71.2 percent, and nonsquamous, 69.2 percent ). In cohort A, 9 people (8.0 percent) had grade 3 pneumonitis, while in cohort B, 7 people (6.9%) had it. Treatment-related AEs of grade 35 occurred in 72 patients (64.3%) in cohort A and 51 (50.0%) in cohort B.
Final Thoughts:
Pembro with cCRT continues to show good anticancer effectiveness and acceptable safety in patients with previously untreated, locally progressed, stage III NSCLC with prolonged follow-up, independently of PD-L1 TPS and tumor histology. NCT03631784, NCT03631784, NCT03631784, NCT03631784, NCT03