Pembrolizumab Plus Concurrent Chemoradiation Continues to Induce Durable Responses in Previously Untreated Stage III NSCLC

Article

Patients with previously untreated, locally advanced stage 3 non–small cell lung cancer continue to derive a benefit from pembrolizumab with concurrent chemoradiation followed by additional pembrolizumab after more than 2 years of follow-up.

Updated findings from the KEYNOTE-799 trial (NCT03631784) continue to show that treatment with pembrolizumab (Keytruda) plus concurrent chemoradiation followed by pembrolizumab monotherapy remains efficacious in patients with previously untreated, locally advanced stage III non–small cell lung cancer (NSCLC), according to a presentation at the 2022 American Society of Clinical Oncology Annual Meeting.

Findings also demonstrated that treatment with the study regimen led to 2-year progression-free survival (PFS) rates of 55.3% in patients with squamous and nonsquamous histology (cohort A) and 60.6% in patients with nonsquamous histology only (cohort B).

Moreover, the overall survival rate at 2 years was 64.3% in cohort A and 71.2% in cohort B.

The typical standard of care for patients with unresectable, stage 3 NSCLC consists of concurrent chemoradiation followed by consolidation therapy with durvalumab (Imfinzi), according to the study authors.

Here, the investigators presented additional findings from the KEYNOTE-799 trial. Previous results from a primary analysis of the data with a cutoff date of Oct. 28, 2020, showed that cohort A (n = 112) had an overall response rate (ORR) of 70.5% and cohort B achieved an ORR of 70.6%. At the time of the primary analysis, a small proportion of cohort A (8.0%) and cohort B (6.9%) experienced grade 3 or worse pneumonitis.

The updated findings include an additional 1-year of follow-up for all enrolled patients.

To be enrolled onto KEYNOTE-799, patients had to be aged 18 years or older, have stage 3A-C, unresectable, locally advanced, pathologically confirmed, previously untreated NSCLC. Patients were not permitted to have received prior systemic immunosuppressive therapy within 7 days of enrollment. In total, 216 patients enrolled onto the trial, however only 214 received treatment.

Patients in cohort A (n = 112; median age, 66 years) received 200 mg of pembrolizumab every 3 weeks (Q3W) plus 200 mg/m2 of paclitaxel Q3W and carboplatin AUC6 Q3W during the first cycle. From treatment cycles 2-3, the cohort received the same dosage of pembrolizumab as well as 45 mg/m2 of paclitaxel once weekly (QW) plus carboplatin AUC2 QW and thoracic radiotherapy (60 Gy in 30-daily, 2-Gy fractions 5 days a week). This was then followed by 200 mg of pembrolizumab Q3W until cycle 17 was completed or disease progression, unacceptable adverse events (AEs), illness that prevented further treatment or study withdrawal.

Cohort B (n = 102; median age, 64 years) received a slightly different regimen. Patients in this cohort received pembrolizumab 200 mg Q3W plus pemetrexed 500 mg/m2 Q3W and 75 mg/m2 of cisplatin Q3W during cycle 1. Cycles 2-3 consisted of the same treatments and doses with thoracic radiotherapy added to the regimen. And then for cycles 4-17, patients received 200 mg of pembrolizumab Q3W until the last cycle was completed or any occurrence that would result in treatment withdrawal.

With an added year of follow-up, the ORR in both overall patient populations increased slightly — 71.4% (95% CI, 62.1-79.6) in cohort A and 75.5% (95% CI, 66.0-83.5) in cohort B. In terms of ORR by cancer stage, patients with stage 3A derived the most benefit — 73.2% (95% CI, 57.1-85.8) in cohort A and 76.9% (95% CI, 60.7-88.9) in cohort B.

Patients with an ongoing response to treatment dropped from 78.8% at 12 months to 64% at 24 months in cohort A. There was also a decrease in cohort B, but not as significant (74.8% vs 68.7%, respectively).

In terms of treatment-related AEs, 93.8% of cohort A and 97.1% of cohort B experienced an event at any grade.

“Pembrolizumab plus [concurrent chemoradiation therapy] followed by pembrolizumab represents a promising therapy for patients with previously untreated, locally advanced, stage 3 NSCLC,” the study authors concluded.

Reference

Reck M, Lee KH, Frost N, et al. Two-year update from KEYNOTE-799: Pembrolizumab plus concurrent chemoradiation therapy (cCRT) for unresectable, locally advanced, stage III NSCLC. J Clin Oncol. 2022;40(suppl 16):8508. doi:10.1200/JCO.2022.40.16_suppl.8508

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