The incidence of hyperprogressive disease (HPD) after PD-1 blockade appears similar in patients with sarcoma and those with other solid tumors, according to a study published in Clinical Cancer Research.1

Prior studies have shown HPD after PD-1 blockade in patients with various tumor types.2,3 In the current study, 11% of sarcoma patients developed HPD, and these patients had similar characteristics as those with progressive disease (PD).

The researchers conducted a pooled analysis of trial data to investigate HPD in sarcoma patients. The analysis included 134 patients with unresectable or metastatic sarcoma who were treated with PD-1 inhibitors on 4 prospective trials from 2015 to 2019. 


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The treatment regimens patients received included nivolumab with or without ipilimumab (n=20), pembrolizumab plus talimogene laherparepvec (T-VEC; n=18), nivolumab plus bempegaldesleukin (n=68), and pembrolizumab plus epacadostat (n=28).

Results

The median follow-up was 33 months. The overall response rate was 16%, and 30% of responses lasted more than 2 years. The rate of stable disease (SD) was 36%, the PD rate was 34%, and 11% of patients had HPD.

There were 11 cases of HPD in the nivolumab-bempegaldesleukin trial and 4 in the pembrolizumab-epacadostat trial. There were no cases of HPD in the nivolumab-ipilimumab trial or the pembrolizumab plus T-VEC trial (P =.03). In the nivolumab-bempegaldesleukin trial, 5 patients were not evaluable for HPD due to inadequate imaging.

For the entire cohort, the median progression-free survival (PFS) was 2 months. The median PFS was 15.0 months for responders, 5.5 months for patients with SD, 1.6 months for patients with PD, and 1.6 months for patients with HPD.

The median overall survival (OS) was 16 months for the entire cohort. The median OS was not reached for responders, 18 months for patients with SD, 7.7 months for those with PD, and 5.9 months for those with HPD (PD vs HPD, P =.34).

The researchers found that patients with HPD were clinically and biologically similar to patients with PD. Sarcoma subtypes, sites of metastasis, clinical course, and genomic alterations were similar between the groups. The only difference was that HPD tumors were smaller at baseline.

“Further research is required to establish whether HPD is a biologically distinct phenomenon and whether a theoretical risk of HPD should influence patient management,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Klemen ND, Hwang S, Bradic M, et al. Long term follow-up and patterns of response, progression and hyperprogression in patients after PD-1 blockade in advanced sarcoma. Clin Cancer Res. Published online December 29, 2021. doi:10.1158/1078-0432.CCR-21-3445
  2. 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. JAMA Oncol. 2018;4(11):1543-1552. doi:10.1001/jamaoncol.2018.3676
  3. Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920-1928. doi:10.1158/1078-0432.CCR-16-1741