Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes Journal Article
| Authors: | Laccetti, A. L.; Garmezy, B.; Xiao, L.; Economides, M.; Venkatesan, A.; Gao, J.; Jonasch, E.; Corn, P.; Zurita-Saavedra, A.; Brown, L. C.; Kao, C.; Kinsey, E. N.; Gupta, R. T.; Harrison, M. R.; Armstrong, A. J.; George, D. J.; Tannir, N.; Msaouel, P.; Shah, A.; Zhang, T.; Campbell, M. T. |
| Article Title: | Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes |
| Abstract: | Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA-approved as front-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol and post-front-line experience with combination TKI–IO approaches. Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post-first-line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression-free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion: To our knowledge, this is the first case series reporting off-label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. |
| Keywords: | adult; cancer survival; clinical article; treatment outcome; treatment response; aged; unclassified drug; overall survival; drug tolerability; fatigue; histopathology; salvage therapy; bevacizumab; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; bone metastasis; cancer radiotherapy; lymph node metastasis; demography; interleukin 2; ipilimumab; progression free survival; mucosa inflammation; nausea; medical record review; retrospective study; renal cell carcinoma; nephrectomy; protein tyrosine kinase inhibitor; arthralgia; pneumonia; rash; cancer center; liver metastasis; radiologist; immunotherapy; medical research; pazopanib; colitis; texas; hypothyroidism; axitinib; disease control; tyrosine kinase inhibitor; mammalian target of rapamycin inhibitor; hand foot syndrome; peritoneum metastasis; kidney metastasis; cytopenia; proteinuria; skin metastasis; electrolyte disturbance; north carolina; adrenal metastasis; soft tissue metastasis; combination; intermediate risk patient; metastatic renal cell carcinoma; hypertransaminasemia; metastasis resection; nephritis; body weight loss; immune checkpoint inhibitor; response evaluation criteria in solid tumors; cabozantinib; nivolumab; very elderly; lenvatinib; human; male; female; priority journal; article; patient history of surgery; artificial embolization; programmed death 1 receptor inhibitor |
| Journal Title: | Cancer Medicine |
| Volume: | 10 |
| Issue: | 7 |
| ISSN: | 2045-7634 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2021-04-01 |
| Start Page: | 2341 |
| End Page: | 2349 |
| Language: | English |
| DOI: | 10.1002/cam4.3812 |
| PUBMED: | 33650321 |
| PROVIDER: | scopus |
| PMCID: | PMC7982609 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
