Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria

Eur J Cancer. 2018 Jan:88:38-47. doi: 10.1016/j.ejca.2017.10.017. Epub 2017 Nov 26.

Abstract

Background: Immune checkpoint inhibitors are an important tool in the therapeutic strategy against metastatic non-small cell lung cancer (NSCLC); however, radiological evaluation is challenging due to the emergence of atypical patterns of responses. Several evaluation criteria have been proposed, such as the Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune -related RECIST (irRECIST) and iRECIST, but have not been systematically compared in a homogeneous population.

Patients and methods: We conducted a monocentric retrospective analysis of consecutive advanced NSCLC patients treated with an anti-programmed cell death-1 or anti-program death-ligand 1. Response patterns and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were described, and associations of response patterns and clinical outcome were explored.

Results: Overall, 160 patients treated between February 2013 and October 2016 were included. Atypical responses were observed in 20 patients (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease, and 123 patients (77%) exhibited progression. Eighty progressive patients were assessable for irRECIST and iRECIST: 15 patients were assessed differently; however, only three (3.8%) mismatches with a theoretical impact on the therapeutic decision were identified. Patients with PsPD or dissociated response had higher overall survival than patients with true progression.

Conclusion: Atypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1 evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of the progressive patients. Immune-related RECIST and iRECIST identified these unconventional responses, with a 3.8% discrepancy rate.

Keywords: Carcinoma; Imaging evaluation; Immunotherapy; Non–small cell lung cancer.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism
  • Response Evaluation Criteria in Solid Tumors
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor