4174 - Primary renal tumour shrinkage in patients (pts) who did not undergo upfront cytoreductive nephrectomy (uCN): subgroup analysis from the phase 3 JAVELIN Renal 101 trial of first-line avelumab + axitinib (A + Ax) vs sunitinib (S) for advanced renal cell carcinoma (aRCC)

Background

On the basis of noninferiority outcomes for pts with metastatic disease who received S vs pts who underwent uCN followed by S (Mejean NEJM 2018), the role of uCN in pts with metastatic RCC who require systemic therapy has been revised. However, the activity of new combination treatments on the primary tumour is unknown. The JAVELIN Renal 101 trial (NCT02684006) demonstrated longer progression-free survival (median 13.8 vs 8.4 mo; HR 0.69; p < 0.001) and higher objective response rate (51% vs 26%) with A + Ax vs S in pts with aRCC; benefit was observed in all risk sugroups and in pts irrespective of prior CN (Motzer NEJM 2019; Choueiri ASCO-GU 2019).

Methods

886 eligible pts with clear cell aRCC, no prior systemic therapy for aRCC, and ECOG PS 0-1 were randomised 1:1 to receive either A + Ax (N = 442) or S (N = 444) following a standard dose and schedule. We performed a post hoc analysis to investigate the extent of primary renal tumour shrinkage in pts with renal target lesions who did not undergo uCN.

Results

Of 886 pts, 179 (20.2%) did not undergo uCN; 55/90 on the A+ Ax arm and 62/89 on the S arm had renal target lesions. Baseline characteristics were balanced between the 2 arms in this subgroup; 0.9%/59.8%/39.3% had favourable/intermediate/poor IMDC risk. Of the pts with renal target lesions who did not undergo uCN in the A + Ax vs S arms, 34.5% vs 9.7% had ≥30% shrinkage for best % change in renal target lesions from baseline. The median time to ≥ 30% shrinkage in renal target lesions was 4.4 vs 7.1 mo, respectively. The agreement rate between pts with ≥30% shrinkage in the renal target lesion and ≥30% shrinkage in all target lesions was 83.6% vs 82.3%, respectively. Results of ongoing biomarker analyses will be presented.

Conclusions

A + Ax resulted in greater shrinkage of the primary renal tumour vs S in pts with aRCC who did not undergo uCN. This is the first report of the efficacy of immuno-oncology + tyrosine kinase inhibitor therapy on the primary tumour in the context of metastatic RCC and provides insight into future neoadjuvant strategies in aRCC.

Clinical trial identification

NCT02684006 February 17, 2016.

Editorial acknowledgement

ClinicalThinking, funded by Pfizer Inc. and Merck Healthcare KGaA.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc. in alliance with Merck Healthcare KGaA.

Disclosure

L. Albiges: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Peloton Therapeutics; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis. B.I. Rini: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): GNE/Roche; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Peloton. J.B.A.G. Haanen: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Neon Therapeutics; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Bayer; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Gadeta DV; Advisory / Consultancy: Celsius Therapeutics; Advisory / Consultancy: AstraZeneca/MedImmune. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Inc.; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Bristol-Myers Squibb (BMS); Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy: Merck. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: EMD Serono. S. Negrier: Honoraria (self): Pfizer; Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Eusa Pharma. J. Bedke: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: Eusa Pharma; Advisory / Consultancy: Nektar. M.A. Bilen: Advisory / Consultancy: Exelixis; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Tricon Pharmaceuticals; Research grant / Funding (institution): Peleton; Research grant / Funding (institution): Pfizer. P. Nathan: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Immunocore; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. Y. Tomita: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (self): Sanofi-Aventis; Honoraria (self): BMS; Advisory / Consultancy: Taiho; Advisory / Consultancy: MSD; Research grant / Funding (institution): Takeda. B. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. K.A. Ching: Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Pfizer Inc. A. Chudnovsky: Full / Part-time employment: Pfizer, Inc. P.B. Robbins: Full / Part-time employment: Pfizer, Inc. A. di Pietro: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer, Inc. D. Thomaidou: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer, Inc. T.K. Choueiri: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Foundation Medicine; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Cerulean Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Prometheus Laboratories; Honoraria (self), Advisory / Consultancy: Alligent; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Corvus Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Alexion Pharmaceuticals; Research grant / Funding (institution): Seattle Genetics/Astellas; Honoraria (self), Advisory / Consultancy: Sanofi/Aventis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Peloton Therapeutics; Honoraria (self), Advisory / Consultancy: EMD Serono; Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Leadership role: NCCN; Leadership role: Kidney Cancer Association; Honoraria (self), Advisory / Consultancy: UptoDate; Honoraria (self), Advisory / Consultancy: Michael J. Hennessy Associates; Honoraria (self), Advisory / Consultancy: ASCO; Honoraria (self), Advisory / Consultancy: Harborside Press; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Analysis Group; Honoraria (self), Advisory / Consultancy: PlatformQ Health; Honoraria (self), Advisory / Consultancy: Clinical Care Options; Honoraria (self), Advisory / Consultancy: Navinta Healthcare; Honoraria (self), Advisory / Consultancy: Kidney Cancer Journal; Honoraria (self), Advisory / Consultancy: Lpath; Honoraria (self), Advisory / Consultancy: NEJM; Honoraria (self), Advisory / Consultancy: Lancet Oncology; Honoraria (self), Advisory / Consultancy: HERON; Honoraria (self), Advisory / Consultancy: Lilly; Research grant / Funding (institution): TRACON Pharma; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Calithera Biosciences; Full / Part-time employment: Dana Farber Cancer Hospital. All other authors have declared no conflicts of interest.