Background: Immune checkpoint inhibitors (ICI) have tremendously changed the paradigm of management for advanced stage cancers such as lung malignancies. Two unique patterns of response to immunotherapy have recently been described: pseudoprogression and hyperprogression. Hyperprogression is defined as a 2-fold increase in the tumor growth rate within 8 weeks of ICI administration.
Case Presentation : A 58-year-old female presented with left-sided chest pain for two weeks. CT-chest with contrast showed an 8.6 × 6.1 × 7.6 cm3 left upper lobe mass. An endobronchial ultrasound (EBUS)-guided biopsy revealed poorly differentiated adenocarcinoma. Staging FDG-18 PET scan revealed no metastases, resulting in a stage IIIA Non-Small Cell Lung Cancer (T4N0M0) on presentation. Per NCCN guidelines, she received standard of care definitive concurrent chemoradiation. Follow-up scans showed significant response in local disease without distant metastases. The patient then received cycle 1 consolidation immunotherapy with Durvalumab. Two weeks after, she complained of fatigue, new-onset headache and worsening dyspnea. CT-chest revealed development of a right upper lobe opacity, MRI brain showed the development of multiple brain metastases and PET scan uncovered hypermetabolic activity in a left adrenal nodule. Biopsy of the adrenal nodule confirmed metastatic adenocarcinoma, consistent with hyperprogression. Molecular testing of the standard lung tumor markers was negative (EGFR(-) ALK(-) BRAF(-) ROS-1 (-) PD-L1 <1%). Given her hyperprogression on ICIs, we opted to treat her with systemic chemotherapy with Carboplatin and Pemetrexed.
Conclusion: We herein report the first case report of hyperprogression in the non-metastatic setting. As ICIs become more incorporated in oncology practice, physicians should be aware of hyperprogression and its diagnostic criteria. Current molecular predictors of hyperprogression include MDM2/4 and EGFR mutations. Further elucidation of predictors of hyperprogressive disease will help guide better selection of ICI candidates.
