Adverse Events With Checkpoint Inhibitors Tied To Lung-Cancer Survival

Treatment of non-small-cell lung cancer (NSCLC) with immune-checkpoint inhibitors may prompt multisystem immune-related adverse events, but this appears to be good news, a retrospective study in JAMA Oncology suggests.

"There is a growing body of literature showing that the development of immune-related adverse events (irAEs) may associate with improved survival outcomes from immunotherapy for NSCLC," said Dr. Jarushka Naidoo of Johns Hopkins University, in Baltimore, Maryland.

"For the first time," she told Reuters Health by email, "we show that the development of more than one irAE may be associated with an incremental improvement in survival outcomes... even when adjusting for treatment duration."

To characterize irAEs linked to anti-programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune-checkpoint inhibitors (ICIs), Dr. Naidoo, also at Beaumont Hospital in Dublin, Ireland, and colleagues studied data from five institutions.

They included 623 NSCLC patients (median age, 66 years) treated with anti-PD-1/-PD-L1 ICIs alone or in combination with another anticancer agent. Of these, 148 (24%) developed one irAE and 58 (9.3%) developed multisystem irAEs.

Among the most common irAEs in patients receiving anti-PD-1/-PD-L1 monotherapy were pneumonitis, thyroiditis and dermatitis. In patients receiving ICI combinations these were pneumonitis, diarrhea/colitis and dermatitis.

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Only one patient in the combination group had multisystem irAEs. In the monotherapy group, the most common patterns of such events were pneumonitis thyroiditis (14%), hepatitis thyroiditis (10%) and dermatitis pneumonitis (10%).

The median progression-free survival (PFS) was 10.9 months in those with multisystem irAEs, 5.1 months in those with one irAE and 2.8 months in those with none (P<0.001). Overall survival (OS) was 21.8 months, 12.3 months and 8.7 months, respectively.

In multivariable models allowing for ICI duration, adjusted hazard ratios for OS were 0.86 for one irAE (P=0.26) and 0.57 for multisystem irAEs (P=0.005).

Overall, concluded Dr. Naidoo , "This is an area that has not previously been described in patients with NSCLC. These data inform clinicians of which irAEs involving different organ systems may occur within the same patient with NSCLC after being treated with immunotherapy."

Dr. Hossein Borghaei of Fox Chase Cancer Center, in Philadelphia, told Reuters Health that such reactions could be considered a "biological indicator that the immune system is activated leading to adverse events but also possibly giving us disease control."

Dr. Borghaei, who is chief of the division of thoracic medical oncology and was not involved in the study, added, "This would be a simplified explanation. One has to consider that the disease control and adverse events could be happening for other reasons. This study also suggests that duration of therapy can also be associated with higher likelihood of an event."

Nevertheless, he concluded, "We have had reports similar to this although to my recollection not as large, that side effects arising from other treatments could be associated with better clinical outcomes in lung cancer."

The study did not have commercial funding. Several of the authors report ties to ICI makers.

—David Douglas

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