ASCO GU 2018: Assessing The Quality-adjusted Time Without Symptoms of Disease Progression or Toxicity (Q-TWiST) In Immuno-Oncology: An Application to Nivolumab vs. Everolimus in Previously Treated Advanced RCC

San Francisco, CA (UroToday.com) At this morning’s GU ASCO kidney cancer poster session, Ruchit Shah and colleagues presented results from the assessment of quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) among patients treated with nivolumab or everolimus in advanced RCC patients. Traditional progression definitions based on the RECIST 1.1 criteria may lead to a premature declaration of progression due to tumor flare or pseudo-progression effects associated with immuno-oncology drugs, especially among patients with solid tumors such as RCC. The objective of this study was to compare the Q-TWiST between nivolumab and everolimus, using both traditional and novel immuno-oncology relevant definitions of progression.

For this study, the authors utilized the CheckMate 025 data [1], an RCT assessing nivolumab vs everolimus among pre-treated patients with RCC. At ≤45 months of follow up, overall survival (OS) was partitioned into three health states: TWiST, TOX (time with grade ≥3 toxicity after randomization but before progression), and REL (time after progression):

The following REL definitions were considered to declare progression:

1. RECIST 1.1 criteria (i.e., traditional Q-TWiST)
2. Increase in tumor burden of ≥25% from nadir
3. Treatment discontinuation
4. ≥2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Cancer Index-Diseases related Symptoms (FKSI-DRS) score
5. Any combination of ≥2 out of 3 criteria (traditional progression, treatment discontinuation, FKSI-DRS reduction of ≥2-points from baseline).

Mean Q-TWiST was calculated by weighting the restricted mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Relative Q-TWiST gain (Q-TWIST difference divided by mean everolimus OS) was calculated. The authors found that compared to everolimus, nivolumab patients had statistically significant improvements in Q-TWiST based on all definitions: 1) traditional Q-TWiST: 3.3 months (relative gain: 14.4%); 2) 3.5 months (relative gain: 15.3%); 3) 4.3 months (relative gain: 18.7%), 4) 4.8 months (relative gain: 20.9%); and 5) 4.8 months (relative gain: 20.9%).

The authors concluded that regardless of progression definition, nivolumab resulted in a statistically significant and clinically important gain in quality adjusted OS compared to everolimus. These gains were greater when using progression definitions that incorporate more immuno-oncology relevant response definitions and/or treatment discontinuation information.

Speaker: Ruchit Shah, Pharmerit International, Bethesda, MD

Co-Authors: Marc Botteman, Caitlyn Solem, Linlin Luo, Justin Doan, David Cella, Robert J. Motzer

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

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