Ferrara R, et al. - Researchers investigated patients with advanced non–small cell lung cancer (NSCLC) treated with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors for hyperprogressive disease (HPD) in comparison to those treated with single-agent chemotherapy. They also assessed the association between treatment and HPD. Findings revealed that compared to chemotherapy, PD-1/PD-L1 inhibitors treatment was more commonly associated with HPD in pretreated patients with NSCLC, which in turn was associated with a high metastatic burden and poor prognosis.

Methods

• Pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (8 institutions) or single-agent chemotherapy (4 institutions) in France treated between August 4, 2011, and April 5, 2017, were studied retrospectively in this multicenter study.
• For this study, researchers required measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on at least 2 computed tomographic scans before treatment and 1 computed tomographic scan during treatment.
• Calculation of tumor growth rate (TGR) before and during treatment and variation per month (ΔTGR) was performed.
• Disease progression at the first evaluation with ΔTGR exceeding 50% defined hyperprogressive disease.
• Assessment of the HPD rate in patients treated with IO or chemotherapy was performed as the primary end point.

Results

• Researchers identified 406 eligible patients treated with PD-1/PD-L1 inhibitors (63.8% male); 46.3% (n = 188) were 65 years or older, 72.4% (n = 294) had nonsquamous histology, and 92.9% (n = 377) received a PD-1 inhibitor as monotherapy in second-line therapy or later.
• Observations revealed the median follow-up of 12.1 months (95% CI, 10.1-13.8 months), and the median overall survival (OS) of 13.4 months (95% CI, 10.2-17.0 months).
• HPD was detected in 56 patients (13.8%).
• In 4.7% (n = 19) of the population, they observed pseudoprogression.
• They noted that hyperprogressive disease was significantly associated with more than 2 metastatic sites before PD-1/PD-L1 inhibitors compared with non-HPD (62.5% [35 of 56] vs 42.6% [149 of 350]; P=.006).
• Significantly lower OS was noted for patients experiencing HPD within the first 6 weeks of PD-1/PD-L1 inhibitor treatment compared with patients with progressive disease (median OS, 3.4 months [95% CI, 2.8-7.5 months] vs 6.2 months [95% CI, 5.3-7.9 months]; hazard ratio, 2.18 [95% CI, 1.29-3.69]; P=.003).
• They classified 3 (5.1%) patients as having HPD among the 59 eligible patients treated with chemotherapy.