e14600 Background: RECIST 1.1 is the standard method for tumor response assessment but may not adequately capture atypical radiologic response patterns observed with immunotherapy. We evaluated the frequency and prognostic significance of atypical responses using lesion-level longitudinal assessment in patients with advanced cancer treated with immunotherapy. Methods: We retrospectively analyzed patients with advanced solid tumors enrolled in seven phase I immunotherapy trials who underwent serial lesion-level radiologic assessment using an institutional tumor-tracking system interface. All target and non-target lesions were tracked across serial imaging studies. RECIST 1.1 responses were assessed. Atypical response patterns were defined as: mixed response (MR), concurrent ≥30% decrease in ≥1 lesion with ≥20% increase in ≥1 other lesion; oligoprogression (OP), progression in 1–3 lesions with stability or response in remaining lesions; pseudoprogression (PP), RECIST 1.1 progressive disease (PD) followed by subsequent stabilization or response; and hyperprogression (HP), ≥50% increase in tumor burden within 6–9 weeks of therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression models. Results: Among 142 evaluable patients, 41 (28.9%) exhibited an atypical response: MR in 28 (19.7%), OP in 6 (4.2%), PP in 5 (3.5%), and HP in 2 (1.4%). At the time MR was identified, 64% of patients met RECIST PD; however, 44% continued treatment beyond PD and derived clinical benefit. Compared with patients achieving RECIST complete or partial response (non-MR), MR was associated with shorter PFS (HR 3.57; 95% CI, 1.45–9.09; p = 0.0056) and OS (HR 5.26; 95% CI, 1.41–20.00; p = 0.0134). In contrast, compared with RECIST PD patients (non-MR), MR was associated with longer PFS (HR 0.29; 95% CI, 0.16–0.53; p < 0.0001) and OS (HR 0.20; 95% CI, 0.10–0.41; p < 0.0001). PFS and OS did not differ between MR and RECIST stable disease (non-MR) (p = 0.19 and p = 0.29, respectively). Conclusions: Atypical radiologic response patterns occur in nearly one-third of patients treated with immunotherapy and are not adequately characterized by the limited surrogate lesions assessed by RECIST 1.1. MR represents a distinct intermediate prognostic group, while PP and HP are rare. Lesion-level longitudinal assessment may improve treatment decision-making in immunotherapy trials and become the basis for future disease response criteria. RECIST 1.1 Response characteristics in patients with mixed response. Category No. of Patients % RECIST 1.1 best response Partial response (PR) 7 25.0 Stable disease (SD) 16 57.1 Progressive disease (PD) 5 17.9 Objective response (all PRs) by metastatic site With liver metastases (n=19) 2 10.5 Without liver metastases (n=9) 5 55.6 With lymph node involvement (n=14) 6 42.9 Without lymph node involvement (n=10) 1 10.0
Torrado et al. (Thu,) studied this question.