Papillary renal cell carcinoma

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Note: these are regimens tested in histology-specific populations, please see the main RCC page for other regimens.

3 regimens on this page 3 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Kidney Cancer.

Metastatic disease, first-line

Cabozantinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pal et al. 2021 (SWOG S1500)	2016-2019	Randomized Phase 2 (E-switch-ic)	1. Sunitinib	Seems to have superior PFS (primary endpoint) Median PFS: 9 vs 5.6 mo (HR 0.60, 95% CI 0.37-0.97)
			2. Crizotinib 3. Savolitinib	Not reported

Note: SWOG S1500 was also open to previously treated patients (maximimum of one line of therapy) but almost all patients were untreated at time of study enrollment.

Targeted therapy

• Cabozantinib (Cabometyx) 60 mg PO once per day on days 1 to 28

28-day cycles

References

1. SWOG S1500: Pal SK, Tangen C, Thompson IM Jr, Balzer-Haas N, George DJ, Heng DYC, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason GA, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, Lara PN Jr. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 20;397(10275):695-703. Epub 2021 Feb 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02761057

Erlotinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Gordon et al. 2009 (SWOG S0317)	2005-2006	Phase 2	ORR: 11% (95% CI 3-24%)

Targeted therapy

• Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28

28-day cycles

References

1. SWOG S0317: Gordon MS, Hussey M, Nagle RB, Lara PN Jr, Mack PC, Dutcher J, Samlowski W, Clark JI, Quinn DI, Pan CX, Crawford D. Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol. 2009 Dec 1;27(34):5788-93. Epub 2009 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00060307

Sunitinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pal et al. 2021 (SWOG S1500)	2016-2019	Randomized Phase 2 (C)	1. Cabozantinib	Seems to have inferior PFS
			2. Crizotinib 3. Savolitinib	Not reported
Choueiri et al. 2020 (SAVOIR)	2017-07 to 2018-11	Phase 3 (C)	Savolitinib	Did not meet primary endpoint of PFS

Note: SWOG S1500 was also open to previously treated patients (maximimum of one line of therapy) but almost all patients were untreated at time of study enrollment.

Biomarker eligibility criteria

• SAVOIR: Chromosome 7 gain, MET amplification, MET kinase domain variations, or HGF amplification without any co-occurring FH or VHL variations

Targeted therapy

• Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28

42-day cycles

References

1. Retrospective: Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, Zhou M, Rini BI, Bukowski RM, Escudier B. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008 Jan 1;26(1):127-31. link to original article PubMed
2. SAVOIR: Choueiri TK, Heng DYC, Lee JL, Cancel M, Verheijen RB, Mellemgaard A, Ottesen LH, Frigault MM, L'Hernault A, Szijgyarto Z, Signoretti S, Albiges L. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Aug 1;6(8):1247-1255. Erratum in: JAMA Oncol. 2020 Sep 1;6(9):1473. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03091192
3. SWOG S1500: Pal SK, Tangen C, Thompson IM Jr, Balzer-Haas N, George DJ, Heng DYC, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason GA, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, Lara PN Jr. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 20;397(10275):695-703. Epub 2021 Feb 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02761057