Prior Radiotherapy Boosts Advanced NSCLC Pembrolizumab-Related Survival

A history of radiotherapy is associated with extended progression-free and overall survival in patients with advanced non-small-cell lung cancer given pembrolizumab

medwireNews: Advanced non-small-cell lung cancer (NSCLC) patients who have received radiotherapy before beginning treatment with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab achieve significantly better survival outcomes than their counterparts who have not, suggests a secondary analysis of the KEYNOTE-001 trial.

After a median of 32.5 months, progression-free survival (PFS) was a median of 4.4 months for the 42 patients who had received any radiotherapy before their first cycle of pembrolizumab versus 2.1 months for the 55 patients who had never received radiation, giving a significant hazard ratio of 0.56.

And a similar pattern was observed among the 38 patients who had versus the 59 who had not received extracranial radiotherapy (6.3 vs 2.0 months, HR=0.50), say Percy Lee, from the University of California Los Angeles in the USA, and co-investigators.

Overall survival (OS) was also significantly longer in patients with prior radiotherapy, at 10.7 versus 5.3 months and a HR of 0.58. The corresponding values for patients with and without a history of extracranial radiation were 11.6 versus 5.3 months and a significant HR of 0.59.

The researchers note that 45% of the patients developed pulmonary toxicity during pembrolizumab therapy but the frequency of any pulmonary side effects or grade 3 and more severe pulmonary events did not differ between the patients who had and had not received thoracic radiotherapy.

Further analysis suggested that three patients with a history of thoracic radiotherapy may have developed treatment-related pulmonary toxicity versus just one patient who had not received thoracic radiation.

“[T]hese data represent the most compelling and largest clinical data to date on the effect of previous radiotherapy on enhancing the activity of anti-PD-1 therapy”, the authors comment in The Lancet Oncology.

“Our findings are supported by dozens of preclinical studies showing synergistic antitumour activity with the combination of radiotherapy and immunotherapy, and suggest that the combination of radiotherapy with pembrolizumab has a clinically acceptable safety profile and shows promising activity among patients with advanced NSCLC.”

Dirk De Ruysscher, from University Hospitals Leuven in Belgium, notes in an accompanying comment that the possible beneficial effect appears to have occurred despite pembrolizumab treatment beginning a median of 9.5 months after radiotherapy.

While acknowledging that the phase I subgroup analysis does not allow “definitive conclusions” to be drawn, he agrees that “the results are completely in line with a wealth of consistent high-level preclinical data that suggests combining radiotherapy with a whole spectrum of immune interventions, including checkpoint inhibitors, leads to superior outcomes.”

And the commentator remarks: “If confirmed in randomised studies, radiotherapy might become an integral part of immunotherapy, similar to multiple drug combinations.”

Reference

Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol; Advance online publication 24 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30380-7

De Ruysscher D. Radiotherapy and PD-L1 inhibition in metastatic NSCLC. Lancet Oncol; Advance online publication 24 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30354-6

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