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  • / Predictors of objective response to first-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Results from the international metastatic renal cell database consortium (IMDC).

Predictors of objective response to first-line immuno-oncology combination therapies in metastatic renal cell carcinoma: Results from the international metastatic renal cell database consortium (IMDC).

Abstract Video & Slides Poster

Authors

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Vishal Navani

Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada

Vishal Navani , Matthew Scott Ernst , Connor Wells , Takeshi Yuasa , Kosuke Takemura , Frede Donskov , Naveen S. Basappa , Andrew Lachlan Schmidt , Sumanta K. Pal , Luis A Meza , Lori Wood , D. Scott Ernst , Bernadett Szabados , Rana R. McKay , Andrew James Weickhardt , Cristina Suárez , Anil Kapoor , Jae-Lyun Lee , Toni K. Choueiri , Daniel Yick Chin Heng

Organizations

Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada, BC Cancer Agency, Vancouver, BC, Canada, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan, Aarhus University Hospital, Aarhus, Denmark, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, Department of Medical Oncology & Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, City of Hope Comprehensive Cancer Center, Duarte, CA, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada, Division of Medical Oncology, Department of Oncology, London Regional Cancer Program, London Health Sciences Centre and University of Western Ontario, London, ON, Canada, Barts Cancer Institute, London, United Kingdom, University of California San Diego, La Jolla, CA, Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Melbourne, Australia, Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA

Research Funding

Other Foundation

Background: Predictors of objective response to first-line (1L) immuno-oncology (IO) combination therapies remain elusive. We sought to characterise clinical variables and their association with investigator assessed best overall response. Methods: Using the IMDC, we retrospectively identified patients treated with 1L ipilimumab nivolumab (IPI-NIVO) or approved IO/vascular endothelial growth factor (VEGF) inhibitor combinations (IOVE). Patients were classified, per RECIST v1.1, as responders (complete or partial response (CR or PR)) or non-responders (stable or progressive disease (SD or PD)). Logistic regression was used to adjust for IMDC criteria. Results: Out of 1084 patients, 794 (73%) received IPI-NIVO and 290 (27%) received IOVE (axitinib+pembrolizumab, cabozantinib+nivolumab, axitinib+avelumab, lenvatinib+pembrolizumab). Favourable, intermediate and poor IMDC risk comprised 147 (16%), 517 (55%) and 272 (29%) respectively. Of the 898 patients with evaluable responses, 37 (4%) achieved a best response of CR, 343 (38%) PR, 315 (35%) SD and 203 (23%) PD. Corresponding median overall survival from time of 1L initiation was: not reached, 55.9, 48.1, and 13 months respectively (logrank p < 0.0001). In a multivariable model, lung metastases and cytoreductive nephrectomy (CN) (performed after diagnosis of metastatic disease and before 1L therapy) retained independent association with response, after adjustment for IMDC criteria. Factors not associated with response included (with univariable p values): gender (p = 0.58), age (p = 0.06), sarcomatoid histology (p = 0.99), smoking status (p = 0.39), liver (p = 0.63) and brain (p = 0.12) metastases. As in the VEGF monotherapy era, improved IMDC prognostic risk was associated with response. Results were similar when restricted to the IPI-NIVO cohort. Conclusions: Presence of lung metastases, CN and better IMDC risk group are associated with a higher probability of response to 1L immunotherapy combination regimens. Further work to identify reliable predictors of response to guide treatment selection and patient counselling is warranted.

Clinical Variables
Univariable
Final Multivariable Model*
Odds Ratio
95% CI
p Value
Odds Ratio
95% CI
p Value
Sex
Male vs Female
1.09
0.81-1.48
0.580
Clear Cell
Clear Cell vs Non
1.71
1.07-2.71
0.024
Sarcomatoid
Yes vs No
1.00
0.68-1.46
0.995
Cytoreductive Nephrectomy
Yes vs No
1.57
1.13-2.19
0.007
1.47
1.02-2.11
0.038
Lung Mets
Yes vs No
1.71
1.26-2.31
< 0.001
1.71
1.23-2.37
0.001
Bone Mets
Yes vs No
0.75
0.56-0.99
0.049


Liver Mets
Yes vs No
0.91
0.63-1.32
0.628
IMDC
Poor vs Fav
0.45
0.29-0.71
< 0.001
0.41
0.26-0.64
< 0.001
IMDC
Poor vs Int
0.65
0.46-0.90
0.010
0.62
0.44-0.87
 0.006

*Only variables that retained significance in a multivariable model are shown.

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Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer,Urethral Cancer

Sub Track

Quality of Care/Quality Improvement and Real-World Evidence

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr 310)

DOI

10.1200/JCO.2022.40.6_suppl.310

Abstract #

310

Poster Bd #

D12

Abstract Disclosures

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