Presented in a case report published in the Journal of Oncology Practice is a patient with unresectable, nonmetastatic non-small cell lung cancer (NSCLC) who developed apparent immunotherapy-induced hyperprogressive disease, involving development of distant metastases, shortly following consolidation therapy with a programmed cell death-ligand 1 (PD-L1) inhibitor administered after definitive chemoradiation therapy.1

The clinical phenomenon of rapid tumor growth shortly following treatment with immune checkpoint inhibitor therapy (ie, hyperprogression) has been recently identified, although questions related to the underlying pathophysiology of hyperprogression, as well as whether it represents a distinct clinical entity, remain.  

While current definitions of hyperprogression vary, one includes the following criteria: “time-to-treatment failure <2 months, >50% increase in tumor burden compared with preimmunotherapy imaging, and >2-fold increase in progression pace.”2 However, this case study represents the first report of putative hyperprogression manifesting as the development of distant metastasis following treatment of a patient with nonmetastatic disease with immune checkpoint inhibitor therapy.

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Specifically, this case study described the clinical course of a woman aged 58 years diagnosed with unresectable stage IIIA NSCLC. Following treatment with carboplatin/paclitaxel-based chemoradiation therapy, the patient received a single dose of durvalumab, a PD-L1 inhibitor approved in 2018 by the US Food and Drug Administration (FDA) for patients with unresectable stage III NSCLC without disease progression following platinum-based chemoradiation therapy.3

Two weeks following administration of durvalumab, the patient complained of fatigue and worsening shortness of breath. She was treated with prednisone following evidence suggestive of pseudoprogression on computed tomography scans. However, positron-emission tomography scans followed by biopsy at 5 weeks postadministration of durvalumab revealed an adrenal metastasis; in addition, multiple brain metastases were revealed on brain magnetic resonance imaging performed at approximately 8 weeks following the administration of durvalumab.

The authors of this case study concluded that the patient was likely experiencing disease hyperprogression based on the following criteria:

  • Time to development of distant metastasis was  considerably shorter than the median time observed in the pivotal clinical trial of durvalumab in patients with unresectable stage III NSCLC
  • Distant metastases developed shortly after administration of durvalumab
  • Disease progression was stopped when durvalumab was discontinued

“Current definitions of HPD [hyperprogressive disease] would fail to capture this case of HPD. Oncologic societies should set more sophisticated criteria for hyperprogression to encompass all cases of HPD,” the authors concluded.


  1. Khreis TJ, Azar IH, Patel R, Mehdi SA. Durvalumab-induced hyperprogressive disease in nonmetastatic lung cancer [published online March 18, 2019]. J Oncol Pract. doi: 10.1200/JOP.18.00739
  2. Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin Cancer Res. 2017;23(15):4242-4250.
  3. Durvalumab (Imfinzi®) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2018.