Immune-Modified Response Criteria in Solid Tumours

Analyzis of atezolizumab data in clinical trials including NSCLC, mUC, RCC and melanoma patients may inform additional modifications to response evaluation criteria

A group of international investigators led by F. Stephen Hodi of the Dana-Farber Cancer Institute, Boston, MA, USA analysed data from testing atezolizumab in clinical trials for non–small cell lung cancer (NSCLC), metastatic urothelial carcinoma (mUC), renal cell carcinoma (RCC), and melanoma. Evaluation of progression-free survival (PFS) and patterns of response and progression revealed that allowance for target lesion (TL) reversion from progressive disease (PD) per immune-modified Response Evaluation Criteria In Solid Tumors (imRECIST) may better identify patients with overall survival (OS) benefit. The findings are published in the Journal of Clinical Oncology.

In the study, modifications to imRECIST versus RECIST v1.1 included allowance for best overall response after PD and changes in PD definitions per new lesions (NLs) and non-target lesions. The PFS according imRECIST did not count initial PD as an event if the subsequent scan showed disease control. The investigators evaluated OS by using conditional landmarks in patients whose PFS differed by imRECIST versus RECIST v1.1.

The best overall response was 1% to 2% greater, the disease control rate was 8% to 13% greater, and the median PFS was 0.5 to 1.5 months longer per imRECIST versus RECIST v1.1.

Extension of PFS according imRECIST vs PFS according RECIST v1.1 was associated with longer or similar OS.

Patterns of progression analysis revealed that patients who developed NLs without TL progression had a similar or shorter OS compared with patients with TL progression according to RECIST v1.1. Patients infrequently experienced a spike pattern (TLs increase, then decrease) but had longer OS than patients without TL reversion.

The authors wrote that their results may inform additional modifications to radiographic criteria, including imRECIST, to better reflect efficacy of immune checkpoint inhibitors.

This retrospective analysis confirms the previous experience in patients with melanoma and provides several new insights.

In particular, the results confirm the existence of unusual response patterns with immune checkpoint inhibitors across other tumour types and, given the improved OS, support the designation of non-progression status to patients who have no subsequent signs of disease progression on imaging after initially being considered to have PD. However, the observation that patients with these patterns of response account for a relatively small proportion of all patients responding to anti-PD-1/PD-L1 antibodies also suggests that the risks and benefits of treatment beyond initial progression should be considered carefully, particularly in patients who have reasonable alternative treatment options available.

The current study is limited to a small selection of cancer types and to treatment with a single agent. In order to establish standardised and validated consensus guidelines that is acceptable to regulatory agencies, larger efforts are required, such as the ongoing initiative by the RECIST working group designed to generate a landscape of data from a large portfolio of clinical trials testing many different immune checkpoint inhibitors and combinations across different cancer types.

Reference

Hodi FS, Ballinger M, Lyons B, et al. Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy. Journal of Clinical Oncology 2018; 36(9):850-858. DOI: 10.1200/JCO.2017.75.1644