Pembrolizumab plus cCRT continue to demonstrate antitumour activity in advanced NSCLC

Prof Martin Reck - German Center of Lung Research, Grosshansdorf, Germany

I had the privilege and pleasure to present an update of KEYNOTE-799. KEYNOTE-799 was a phase II trial investigating concurrent pembrolizumab with chemoradiotherapy followed by consolidation with pembrolizumab in patients with stage 3 unresectable non-small cell lung cancer.

What was the study design?

In the KEYNOTE-799 patients with unresectable stage 3 non-small cell lung cancer received one cycle of chemoimmunotherapy followed by simultaneous chemoimmunotherapy and radiotherapy, followed by consolidation treatment with pembrolizumab. In the KEYNOTE-799 patients were assigned to two cohorts, Cohort A with a histology of non-squamous and squamous cell non-small cell lung cancer, and Cohort B with a histology of non-squamous non-small cell lung cancer.

In Cohort A we had a backbone chemotherapy of carboplatin/paclitaxel and in Cohort B we had a backbone chemotherapy of cisplatin and pemetrexed. The primary endpoints of the KEYNOTE-799 were, on the one hand, safety, in particular the rate of grade 3 or higher pulmonary toxicities. The second coprimary endpoint was efficacy assessed by the response rate.

What were the results of this study?

We presented the first results of KEYNOTE-799 some years ago. Here at ELCC we had the five-year update of the trial with more mature results. When we look at the primary endpoint number one, safety, we created a boundary of 10% grade 3 or higher pulmonary toxicities. We only observed a rate of between 6.9% and 8% so we were clearly below this threshold of pulmonary toxicity. The response rate was more than 70% in both cohorts and now with a follow-up of five years we have quite mature efficacy data. When we look on progression free survival we had a median progression free survival of between 29 and 45 months with a four-year progression free survival rate of 39% to 42% and we observed a median overall survival between 35.6 months and 56.7 months with a four-year overall survival rate between 40% and 57%.

What do you think is the clinical significance of these results?

In the KEYNOTE-799 trial we could show that simultaneous chemo/immune/radiotherapy is feasible in selected patients and we also could show that these novel schedules generated a robust ongoing anti-tumour efficacy in patients with advanced stage 3 non-small cell lung cancer.

So this is something which has now moved into a phase III trial, which is the KEYLYNK-012 trial. This trial has completed recruitment and we are waiting for the final readout of the results.