Checkpoint Inhibitor Pneumonitis Risk In Metastatic Lung Cancer Independent of Thoracic Radiation

The frequency of immune-related adverse events in patients undergoing checkpoint inhibitor therapy for metastatic lung cancer is not influenced by use of thoracic radiotherapy

medwireNews: Patients who receive thoracic radiotherapy for metastatic lung cancer during immune checkpoint inhibitor therapy (CPI) may not be at increased risk for pneumonitis and other immune-related adverse events (irAEs), US researchers suggest.

The team from The Massachusetts General Hospital in Boston reviewed medical records for 164 patients with metastatic non-small-cell lung cancer (n=158) or small-cell lung cancer (n=6) who received programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) between 2013 and 2016.

In all, 73 of the patients received thoracic radiotherapy and these patients were similar to the 91 patients who did not receive radiation except with regard to the proportions who had adenocarcinoma (49 vs 75%) and targetable EGFR, ALK or ROS1 mutations (4 vs 16%).

Patients who did and did not receive thoracic radiotherapy had a comparable rate of grade 2 or more severe irAEs (13.7 vs 15.4%), and this was also true for the rates of any-grade pneumonitis (8.2 vs 5.5%) or grade 2 and worse pneumonitis (4.1 vs 3.3%).

Most of the patients given thoracic radiation had undergone treatment a median of 8.6 months before beginning CPI, say Florence Keane and co-authors in JAMA Oncology. But 10 patients received their radiation between CPI cycles or after CPI therapy was complete and six patients underwent more than one course of radiation; none of these patients developed symptomatic pneumonitis.

And among patients given thoracic radiation, the median dose did not significantly differ between the patients who developed pneumonitis and those who did not, at 52.8 versus 50.4 Gy.

Multivariate analysis pointed to a reduced risk of all-cause mortality for patients who had versus had not developed grade 2 or more severe irAEs, with a hazard ratio of 0.45, “possibly reflecting that patients responding to CPIs likely received more cycles of therapy, which may have in turn predisposed them to the toxic effects”, the authors write.

There was also a trend towards a lower risk of all-cause mortality with receipt of thoracic radiotherapy, despite a lower rate of targetable mutations in this group, which Florence Keane et al describe as “intriguing”.

“It has been postulated that lack of antigenic mutations and other mechanisms of immune evasion may underlie resistance to CPIs”, they write. “In certain situations, radiotherapy may potentiate the efficacy of immunotherapy, even restimulating a durable systemic response in disease that had become refractory to CPIs.”

Acknowledging the limitations of their small study, the researchers look forward to results from ongoing trials investigating use of consolidative CPI after definitive chemoradiotherapy and concurrent radiotherapy and CPI.

“Nonetheless, pending prospective validation, our results suggest that [thoracic radiotherapy] does not significantly increase the risk of symptomatic IRAEs, including pneumonitis, compared with CPIs alone”, they conclude.

Reference

Hwang WL, Niemierko A, Hwang KL, et al. Clinical outcomes in patients with metastatic lung cancer treated with PD-1/PD-L1 inhibitors and thoracic radiotherapy. JAMA Oncol; Advance online publication 27 September 2017. doi:10.1001/jamaoncol.2017.3808

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