PD-1/PD-L1 Inhibitors May Increase the Risk of Hyperprogressive Disease in NSCLC
The association between disease progression and PD-1/PD-L1 inhibitors in non-small cell lung cancer is unknown.
Hyperprogressive disease (HPD) may occur with greater frequency among pretreated patients with non-small cell lung cancer (NSCLC) who receive programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors compared with chemotherapy, according to a study published in JAMA Oncology.1
Immunotherapy with PD-1/PD-L1 inhibitors have greatly improved outcomes among patients with cancer, but only a small proportion of patients are eligible for therapy and progression rates are sometimes as high as with conventional therapies. Furthermore, instances of HPD — accelerated tumor growth — have been reported during immunotherapy in nearly a third of patients with head and neck cancer,2 the association between disease progression and PD-1/PD-L1 inhibitors in NSCLC is unknown.
For this retrospective study, researchers evaluated the outcomes of 406 pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors or single-agent chemotherapy. At least 2 computed tomography (CT) scans, 1 at baseline and 1 most recent scan before baseline, and 1 CT during treatment were mandatory for radiological evaluation. HPD was defined as disease progression at the first evaluation with a variable tumor growth rate (ΔTGR) exceeding 50%.
The median follow-up was 12.1 months and the median overall survival (OS) was 13.4 months. Overall, 56 patients (13.8%) met the criteria for HPD, and 19 (4.7%) had pseudo-progressive disease.
Patients with HPD were significantly associated with having at more than 2 metastatic sites prior to initiating PD-1/PD-l1 inhibitor therapy compared with non-HPD patients (62.5% vs 42.6%; P = .006). Patients with HPD within the first 6 weeks of starting PD-1/PD-L1 inhibitor therapy had a median OS of 3.4 months compared with 6.2 months among patients with progression disease (hazard ratio [HR], 2.18; 95% CI, 1.29-3.69; P = .003).
Of the 59 patients who received chemotherapy, 3 (5.1%) developed HPD.
The authors concluded that there may be “a detrimental association of immunotherapy in a subset of patients with NSCLC. Additional studies are needed to characterize the molecular basis of HPD.”
- Ferrara R, Mezquita L, Texier M, et al. Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy [published online September 6, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.3676
- Saâda-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti–PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2017;28(7):1605-1611.