Hyperprogressive Disease in Patients With Advanced Non–Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy

Abstract

Our study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional studies are needed to determine the molecular mechanisms involved in HPD.

Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress?

“…One question that arises is whether or not HPD is unique to immunotherapy. One report suggests that HPD after chemotherapy can occur, albeit at a much lower rate of 5.1% (3/59) (vs. ∼14% after checkpoint blockade in that study) .…”

“…The phenomenon of enhanced progression after checkpoint blockade has been described with different checkpoint blockade agents and in numerous tumor types including, but not limited to, non‐small cell lung, head and neck, breast, gastric, and genitourinary cancers . The fact that various histologies that can be afflicted by HPD suggests that there could be common, histology‐agnostic biologic or molecular mechanism(s).…”

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report

“…Our patient exhibited significant disease progression immediately after the initiation of nivolumab, including the doubling of tumor size (Fig. ) 1 month after treatment, which exceeded the tumor growth rate defined in a previous trial . This case illustrates the importance of elucidating predictive factors and the mechanism behind hyperprogression in order to better risk‐stratify patients undergoing ICI therapy.…”

“…Additionally, in the only retrospective trial with a control arm, the rate of hyperprogression —defined as tumor growth rate exceeding 50% per month before and during treatment—was higher in patients who had received ICI than compared to chemotherapy in advanced non‐small cell lung cancer (13.8% vs. 5.1%) . Hyperprogression was again associated with worse OS compared with those with progressive disease who did not meet the definition for hyperprogression (3.4 vs. 6.2 months) …”

“…One study noted an association with age >65 years, as well as an inverse correlation with tumor progression and growth prior to immunotherapy initiation . However, another trial noted that hyperprogression was more likely to occur in patients with metastatic disease before checkpoint inhibitor initiation . Multiple trials have not found an association with tumor burden prior to initiating checkpoint therapy, tumor histological type, or previous therapies received .…”