According to follow up data presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore, “Pembrolizumab plus cCRT (concurrent chemoradiation therapy) demonstrated antitumor activity in patients with unresectable, locally advanced, stage-III NSCLC.
The phase-II KEYNOTE-799 study enrolled a total of 216 patients with previously untreated, unresectable, pathologically confirmed stage IIIA-C non-small cell lung cancer, with measurable disease per RECIST 1.1. Cohort-A consisted of patients with both squamous and nonsquamous non-small cell lung cancer, while cohort-B included patients with nonsquamous non-small cell lung cancer only.
The enrolled patients in this study were given up to 17 cycles of pembrolizumab, administered at a dose of 200 mg, 3 times per week. Respective patients in cohort-A also received doctor’s option of either paclitaxel or carboplatin three times weekly on cycle-1, and either paclitaxel or carboplatin once weekly along with thoracic radiotherapy on cycles 2 and 3.
The cohort-B’s patients followed the identical dosing schedule for pembrolizumab, with the inclusion of pemetrexed or cisplatin on cycles 1 to 3 and thoracic radiotherapy during cycle 3.
The dual primary endpoints of the study were overall response rate, per RECIST versus 1.1, and the percentage of patients who developed grade-III or higher pneumonitis.
A primary analysis of KEYNOTE-799, conducted following 15 weeks or more of follow up, was presented during the 2020 ASCO Virtual Scientific Program and simultaneously published in the Journal of Clinical Oncology.
In this analysis, conducted after an additional 6 months of follow up, the ORR for cohort-A (n = 112) was 69.6% (95% CI, 60.2-78.0), with 4 patients (3.6%) showing a complete response (CR). The median duration of response (DOR) for this patient population was not reached, however 82.2% of patients (n = 31) showed a duration of response of 12 months or greater.
Response rates in cohort- B (n = 61) were similar, with an ORR of 70.5% (95% CI, 57.4 to 81.5), including 3 patients (4.9%) who achieved a complete response. The median duration of response was not yet reached, though 72.1% (n = 5) of patients demonstrated a duration of response of 12 months or greater.
The median time to response was 2.1 months (range, 1.1 to 7.6) for cohort-A and 2.2 months for cohort-B (range, 1.8 to 10.3).
According to Martin Reck, MD, PhD, of the Lung Clinic Grosshansdorf in Grosshansdorf, Germany, during an oral presentation of the data, “Interestingly, in a substantial number of patients who had to interrupt the treatment earlier, an ongoing control of the disease or an ongoing response was noted in some patients for a couple of months.”
The 12-month PFS rate was noted as 67.7% for cohort-A, with a 12-month OS rate of 81.2%. The 12-month PFS rate and 12-month OS for cohort-B was noted as 65.2% and 88.0%, respectively. Median PFS and median OS were not reached for either cohort.
Overall, 93.8% & 95.0% of patients in cohort-A and cohort-B respectively reported at least 1 treatment-related adverse event. In total, 119 patients reported treatment-related adverse events of grades 3-5, with 54 patients interrupting treatment due to adverse events. 5-patients experienced the treatment-related adverse events that led to death.
Moreover, 17 patients experienced grade 3 or higher pneumonitis, though Reck observed that the most pneumonitis events were able to be tackled.
Reck said that, “The incidence of TRAEs was within the established toxicity profiles of the chemoradiotherapy and pembrolizumab monotherapy.”