Ferrara R, et al. - In this multicenter cohort study, researchers investigated if hyperprogressive disease (HPD), a new pattern of progression recently described in patients with cancer treated with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, was observed in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors vs single-agent chemotherapy and whether there was a link between treatment and HPD. In pretreated patients with NSCLC, HPD was more commonly detected with PD-1/PD-L1 inhibitors vs chemotherapy. Additionally, in patients treated with PD-1/PD-L1 inhibitors, an association of HPD with high metastatic burden and poor prognosis was seen.

Methods

• This was a multicenter retrospective study.
• Participants were pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (eight institutions) or single-agent chemotherapy (four institutions) in France between August 4, 2011 and April 5, 2017.
• Eligible cases were those with measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on at least two computed tomographic scans before treatment and one computed tomographic scan during treatment.
• The calculation of the tumor growth rate (TGR) before and during treatment and variation per month (ΔTGR) was carried out.
• The definition of hyperprogressive disease was disease progression at the first evaluation with ΔTGR exceeding 50%.
• Assessment of the HPD rate in patients treated with IO or chemotherapy was the primary end point.

Results

• This study included a total of 406 eligible patients treated with PD-1/PD-L1 inhibitors (63.8% male), of those, 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.
• The median follow-up and the median overall survival (OS) was 12.1 months (95% CI, 10.1-13.8 months) and 13.4 months (95% CI, 10.2-17.0 months), respectively.
• HPD was present in 56 patients (13.8%).
• In 4.7% (n=19) of the population, pseudoprogression was observed.
• A significant association of hyperprogressive disease with more than 2 metastatic sites before PD-1/PD-L1 inhibitors vs non-HPD was observed (62.5% [35 of 56] vs 42.6% [149 of 350]; P=.006).
• A significantly lower OS was observed among patients experiencing HPD within the first 6 weeks of PD-1/PD-L1 inhibitor treatment vs 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).
• Three (5.1%) of 59 eligible patients treated with chemotherapy, were classified as having HPD.