Efficacy of avelumab + axitinib (A + Ax) vs sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): extended follow-up results from JAVELIN Renal 101


Year:

Session type:

John Haanen1, James Larkin2, Toni Choueiri3, Laurence Albiges1, Brian Rini4, Michael Atkins1, Manuela Schmindinger1, Konstantin Penkov1, Despina Thomaidou1, Jing Wang5, Mariangela Mariani1, Alessandra di Pietro1, Robert Motzer6
1Other, 2Royal Marsden NHS Foundation Trust, 3Dana-Farber Cancer Institute, 4Vanderbilt-Ingram Cancer Center, 5Pfizer, 6Memorial Sloan-Kettering Cancer Center

Abstract

Background

In the phase 3 JAVELIN Renal 101 trial (NCT02684006), treatment-naive patients with aRCC receiving A+Ax showed improved progression-free survival (PFS) and objective response rate (ORR) across International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor) compared with patients receiving S. Here we report updated efficacy results for A+Ax vs S by IMDC risk groups from the third interim analysis.

Method

Patients were randomized 1:1 to receive either A (10 mg/kg intravenously every 2 weeks) plus Ax (5 mg orally twice daily) or S (50 mg orally once daily) for 4 weeks (6-week cycle). Patients were categorized per IMDC risk group into favorable, intermediate, and poor subgroups, and outcomes were assessed for favorable, intermediate, poor, and intermediate + poor. Overall survival (OS) and PFS, ORR, complete response (CR), and duration of response (DoR) per investigator assessment (RECIST v1.1) were assessed.

Results

The study enrolled 886 patients with aRCC. At data cutoff (Apr 2020), median (95% CI) follow-up for OS in the A+Ax was NR (42.2-NE) vs 37.8 (31.4-NE) months with S. The Table shows OS, PFS, ORR, CR, and DOR by IMDC risk group. A+Ax generally showed improved efficacy compared with S across IMDC groups.


IMDC risk group

Favorable

 

A+Ax(N=442)

Favorable

 

S(N=444)

Intermediate

 

A+Ax(N=442)

Intermediate

 

S(N=444)

Poor

 

A+Ax(N=442)

Poor

 

S(N=444)

Intermediate + Poor

A+Ax(N=442)

Intermediate + Poor

S(N=444)

n

94

96

270

276

73

 

71

343

347

mOS(95% CI), mo

 

HR*(95% CI)

 

NE(NE-NE)

 

0.66(0.356-1.22)

NE(39.8-NE)

 

Ref

42.2(33.1-NE)

 

0.84(0.649-1.08)

37.8(29.6-NE)

 

Ref

21.3(14.7-33.1)

 

0.60(0.399-0.912)

11.0(7.8-16.5)

 

Ref

40.0(30.5-NE)

 

0.79(0.636-0.98)

29.5(24.8-38.0)

 

Ref

mPFS(95% CI), mo

 

HR*

(95% CI)

 

20.7

(16.6-26.3)

 

0.71(0.490-1.02)

13.8(11.1-23.5)

 

Ref

12.9(11.1-16.6)

 

0.71(0.578-0.866)

8.4(7.9-10.1)

 

Ref

8.7(5.6-11.1)

 

0.45(0.304-0.678)

4.2(2.8-5.5)

 

Ref

11.1(9.8-14.6)

 

0.66(0.550-0.787)

8.2(6.9-8.4)

 

Ref

ORR(95% CI), %

 

75.5(65.6-83.8)

45.8(35.6-56.3)

59.6(53.5-65.5)

31.2(25.7-37.0)

38.4(27.2-50.5)

15.5(8.0-26.0)

55.1(49.7-60.4)

28(23.3-33.0)

CR, n (%)

9(9.6)

5(5.2)

11(4.1)

8(2.9)

1(1.4)

1(1.4)

12(3.5)

9(2.6)

DoR

(95% CI), mo

 

22.6(15.2-31.7) (n=71)

20.8(14.5-24.9) (n=44)

19.3(13.9-22.1)(n=161)

12.5(7.1-16.6)(n=86)

18.2(6.8-NE)(n=28)

5.6(2.5-8.3)(n=11)

19.3(13.9-22.1) (n=189)

9.8(7.0-15.3) (n=97)

Conclusion

Extended follow-up confirms efficacy benefits of A+Ax vs S across IMDC risk groups in patients with aRCC. Patients continue to be followed up for the final OS analysis.

Impact statement

A+Ax provides an efficacy benefit across IMDC risk groups in patients with aRCC.

© 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.