Apparent Immunotherapy-Induced Hyperprogression in a Patient With Stage III NSCLC – Cancer Therapy Advisor

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.

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.

References

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.