Sustained Response to Immune Checkpoint Inhibitors Could Influence Standard of Care

A new study to be presented at the 2017 Genitourinary Cancers Symposium has found that 42% of patients with advanced renal cell carcinoma (RCC) had a durable response even after they had discontinued treatment early due to side effects.

The programmed death 1 (PD-1) inhibitor nivolumab (Opdivo), has been found to improve survival in patients with metastatic RCC (mRCC), and is administered on a continuous basis until disease progression or toxicity. For the study, the authors continued to follow patients who had stopped treatment with a PD-1/ programmed death ligand-1 (PD-L1) inhibitor due to immune-related adverse events (irAEs).

Of the 19 patients with mRCC who had responded to immune checkpoint inhibitor treatment, 62% had received a PD-1/PD-L1 inhibitor alone and 37% received PD-1/PD-L1 inhibitors in combination with other systemic treatments. Nine patients who responded to a PD-1/PD-L1 inhibitor discontinued treatment because of an irAE—7 of the 9 were treatment naïve. The irAEs reported were joint pain; eye problems; pituitary gland, muscle, heart, liver, pancreas, kidney, or lung inflammation; and diarrhea. Four of the 9 patients (44%) received PD-1/PD-L1 monotherapy for a median duration of 5.5 months (range 4 to 15 months).

Four patients (44%) whose median time on therapy was 9 months (range 4 to 15 months), remained progression free at 20 months (range 10 to 44 months) after they stopped treatment with their PD-1/PD-L1 inhibitor. For the 5 patients (56%) who progressed within 6 months (range 2 to 6 months) of treatment discontinuation, median time on therapy was 4 months (range 3 to 10 months).

Considering the small sample size of the study, additional studies with a larger cohort of patients is definitely warranted. However, the study findings are novel and point to the lasting duration of impact of checkpoint inhibitors. Future studies could be designed to understand the molecular pathogenesis of a durable response in these patients.

“This study is welcome news for patients who are unable to continue immunotherapy as a result of adverse effects,” said Sumanta Pal, MD, who moderated a presscast by the American Society of Clinical Oncology, which is hosting the meeting. “It’s very reassuring to see that some patients may continue to benefit from immunotherapy even if they need to discontinue it. More broadly, these findings call into question the current standard of continuous treatment with immunotherapy, though longer term follow-up of patients is needed.”