Hyperprogressive disease: a distinct effect of immunotherapy?
While it has long been recognized that the majority of cancer discoveries and clinical trials ultimately fail to improve disease outcomes, only rarely have therapies appeared to worsen the clinical course of malignancy. Recent examples include the use of certain molecularly targeted therapies beyond tumors harboring the target genomic alteration. A phase 3 study of the epidermal growth factor receptor (EGFR) inhibitor gefitinib as maintenance therapy after chemoradiation for locally advanced non-small cell lung cancer (NSCLC) demonstrated an overall survival more than eight months worse than maintenance placebo (1). This difference was attributed to cancer- rather than toxicity-related factors. For KRAS or PIK3CA mutant NSCLC, the EGFR inhibitor erlotinib may have worse overall and progression-free survival than placebo (2).