Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial.

Abstract

BACKGROUND:

The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.

OBJECTIVE:

To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.

DESIGN, SETTING, AND PARTICIPANTS:

IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.

INTERVENTION:

Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.

RESULTS AND LIMITATIONS:

Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19-37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6-13.7) mo. The median event follow-up duration was 19.4 (12.9-21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.

CONCLUSIONS:

The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.

PATIENT SUMMARY:

Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.

• Authors: Thomas Powles, Michael B Atkins, Bernard Escudier, Robert J Motzer, Brian I Rini, Lawrence Fong, Richard W Joseph, Sumanta K Pal, Mario Sznol, John Hainsworth, Walter M Stadler, Thomas E Hutson, Alain Ravaud, Sergio Bracarda, Cristina Suarez, Toni K Choueiri, James Reeves, Allen Cohn, Beiying Ding, Ning Leng, Kenji Hashimoto, Mahrukh Huseni, Christina Schiff, David F McDermott
• Journal: European urology (Eur Urol) Vol. 79 Issue 5 Pg. 665-673 (05 2021) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 33678522 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Antibodies, Monoclonal, Humanized
• Vascular Endothelial Growth Factor A
• Bevacizumab
• atezolizumab
• Sunitinib

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols
• Bevacizumab (adverse effects)
• Carcinoma, Renal Cell (drug therapy)
• Disease Progression
• Humans
• Kidney Neoplasms (drug therapy)
• Sunitinib (therapeutic use)
• Vascular Endothelial Growth Factor A