Subgroup Analysis of the AFTER I-O Study: a Retrospective Study on the Efficacy and Safety of Subsequent Molecular Targeted Therapy After Immune-oncology Therapy in Japanese Patients with Metastatic Renal Cell Carcinoma

Overview

Journal Jpn J Clin Oncol

Publisher Oxford University Press

Specialty Oncology

Date 2021 Aug 5

PMID 34350454

Citations 7

Authors

Yoshihiko Tomita

Go Kimura

Satoshi Fukasawa

Kazuyuki Numakura

Yutaka Sugiyama

Kazutoshi Yamana

Sei Naito

Hirokazu Kaneko

Yohei Tajima

Mototsugu Oya

Affiliations

Soon will be listed here.

Abstract

Background: We performed subgroup analyses of the AFTER I-O study to clarify the association of time-to-treatment failure (TTF) and discontinuation reason of prior immune-oncology (I-O) therapy, and molecular targeted therapy (TT) regimen with the outcomes of TT after I-O.

Methods: The data of Japanese metastatic renal cell carcinoma patients treated with TT after nivolumab (NIVO) (CheckMate 025) or NIVO + ipilimumab (IPI) (CheckMate 214) were retrospectively analyzed. The objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS) of TT after I-O were analyzed by subgroups: TTF (<6 or ≥6 months) and discontinuation reason of prior I-O (progression or adverse events), and TT regimen (sunitinib or axitinib). We also analyzed PFS2 of prior I-O and OS from first-line therapy.

Results: The ORR and median PFS of TT after NIVO and NIVO+IPI among the subgroups was 17-36% and 20-44%, and 7.1-11.6 months and 16.3-not reached (NR), respectively. The median OS of TT after NIVO was longer in patients with longer TTF of NIVO and treated with axitinib. Conversely, median OS of TT after NIVO+IPI was similar among subgroups. The median PFS2 of NIVO and NIVO+IPI was 36.7 and 32.0 months, respectively. The median OS from first-line therapy was 70.5 months for patients treated with NIVO and NR with NIVO+IPI. The safety profile of each TT after each I-O was similar to previous reports.

Conclusions: The efficacy of TT after NIVO or NIVO+IPI was favorable regardless of the TTF and discontinuation reason of prior I-O, and TT regimen.

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References

Motzer R, Escudier B, Tomczak P, Hutson T, Michaelson M, Negrier S . Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013; 14(6):552-62. DOI: 10.1016/S1470-2045(13)70093-7. View

Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M . Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study. Jpn J Clin Oncol. 2017; 47(7):639-646. PMC: 5896687. DOI: 10.1093/jjco/hyx049. View

Miyake H, Harada K, Ozono S, Fujisawa M . Assessment of Efficacy, Safety, and Quality of Life of 124 Patients Treated With Axitinib as Second-Line Therapy for Metastatic Renal-Cell Carcinoma: Experience in Real-World Clinical Practice in Japan. Clin Genitourin Cancer. 2016; 15(1):122-128. DOI: 10.1016/j.clgc.2016.06.019. View

Auvray M, Auclin E, Barthelemy P, Bono P, Kellokumpu-Lehtinen P, Gross-Goupil M . Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma. Eur J Cancer. 2019; 108:33-40. DOI: 10.1016/j.ejca.2018.11.031. View

Ishihara H, Takagi T, Kondo T, Fukuda H, Tachibana H, Yoshida K . Efficacy of Axitinib After Nivolumab Failure in Metastatic Renal Cell Carcinoma. In Vivo. 2020; 34(3):1541-1546. PMC: 7279840. DOI: 10.21873/invivo.11943. View

Powles T, Motzer R, Escudier B, Pal S, Kollmannsberger C, Pikiel J . Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer. 2018; 119(6):663-669. PMC: 6173766. DOI: 10.1038/s41416-018-0164-0. View

Ornstein M, Pal S, Wood L, Tomer J, Hobbs B, Jia X . Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2019; 20(10):1386-1394. DOI: 10.1016/S1470-2045(19)30513-3. View

Heng D, Xie W, Regan M, Harshman L, Bjarnason G, Vaishampayan U . External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013; 14(2):141-8. PMC: 4144042. DOI: 10.1016/S1470-2045(12)70559-4. View

Santini D, Stellato M, De Giorgi U, Pantano F, De Lisi D, Casadei C . Clinical Outcomes of Metastatic Renal Carcinoma Following Disease Progression to Programmed Death (PD)-1 or PD-L1 Inhibitors (IO): A Meet-URO Group Real World Study (Meet-Uro 7). Am J Clin Oncol. 2021; 44(3):121-125. DOI: 10.1097/COC.0000000000000791. View

10.

Bracarda S, Hutson T, Porta C, Figlin R, Calvo E, Grunwald V . Everolimus in metastatic renal cell carcinoma patients intolerant to previous VEGFr-TKI therapy: a RECORD-1 subgroup analysis. Br J Cancer. 2012; 106(9):1475-80. PMC: 3341863. DOI: 10.1038/bjc.2012.89. View

11.

Graham J, Shah A, Wells J, McKay R, Vaishampayan U, Hansen A . Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors. Eur Urol Oncol. 2019; 4(1):102-111. DOI: 10.1016/j.euo.2019.11.001. View

12.

Knox J, Barrios C, Kim T, Cosgriff T, Srimuninnimit V, Pittman K . Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol. 2017; 28(6):1339-1345. PMC: 5452072. DOI: 10.1093/annonc/mdx075. View

13.

Dudani S, Graham J, Wells J, Bakouny Z, Pal S, Dizman N . First-line Immuno-Oncology Combination Therapies in Metastatic Renal-cell Carcinoma: Results from the International Metastatic Renal-cell Carcinoma Database Consortium. Eur Urol. 2019; 76(6):861-867. PMC: 6858928. DOI: 10.1016/j.eururo.2019.07.048. View

14.

Tomita Y, Naito S, Sassa N, Takahashi A, Kondo T, Koie T . Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC. Clin Genitourin Cancer. 2020; 18(4):e374-e385. DOI: 10.1016/j.clgc.2020.01.001. View

15.

Harada K, Nozawa M, Uemura M, Tatsugami K, Osawa T, Yamana K . Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan. Int J Urol. 2018; 26(2):202-210. DOI: 10.1111/iju.13830. View

16.

Rao A, Wiggins C, Lauer R . Survival outcomes for advanced kidney cancer patients in the era of targeted therapies. Ann Transl Med. 2018; 6(9):165. PMC: 5985277. DOI: 10.21037/atm.2018.04.44. View

17.

Albiges L, Fay A, Xie W, Krajewski K, Mcdermott D, Heng D . Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur J Cancer. 2015; 51(17):2580-6. DOI: 10.1016/j.ejca.2015.08.017. View

18.

Choueiri T, Motzer R, Rini B, Haanen J, Campbell M, Venugopal B . Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020; 31(8):1030-1039. PMC: 8436592. DOI: 10.1016/j.annonc.2020.04.010. View

19.

Retz M, Bedke J, Bogemann M, Grimm M, Zimmermann U, Muller L . SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11). Eur J Cancer. 2018; 107:37-45. DOI: 10.1016/j.ejca.2018.11.001. View

20.

Tomita Y, Tatsugami K, Nakaigawa N, Osawa T, Oya M, Kanayama H . Cabozantinib in advanced renal cell carcinoma: A phase II, open-label, single-arm study of Japanese patients. Int J Urol. 2020; 27(11):952-959. PMC: 7689847. DOI: 10.1111/iju.14329. View