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. 2021 Nov 1;51(11):1656-1664.
doi: 10.1093/jjco/hyab114.

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

Yoshihiko Tomita  1 , Go Kimura  2 , Satoshi Fukasawa  3 , Kazuyuki Numakura  4 , Yutaka Sugiyama  5 , Kazutoshi Yamana  1 , Sei Naito  6 , Hirokazu Kaneko  7 , Yohei Tajima  8 , Mototsugu Oya  9
Affiliations

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

Yoshihiko Tomita et al. Jpn J Clin Oncol. .

Erratum in

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.

Keywords: ipilimumab; molecular targeted therapy; nivolumab; renal cell carcinoma.

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Figures

Figure 1.
Figure 1.
Progression-free survival (PFS) of targeted therapy (TT) after discontinuation of nivolumab (NIVO) or nivolumab and ipilimumab combination therapy (NIVO+IPI). (a) PFS of TT after discontinuation of NIVO, stratified by time-to-treatment failure (TTF) of NIVO, with a cutoff value at 6 months. (b) PFS of targeted therapy after discontinuation of NIVO, stratified by reason for discontinuation of NIVO, disease progression or adverse events. (c) PFS of TT after discontinuation of NIVO, stratified by TT regimens after NIVO, sunitinib or axitinib. (d) PFS of TT after discontinuation of NIVO+IPI, stratified by TTF of NIVO+IPI, with a cutoff value at 6 months, IMDC all risks. (e) PFS of TT after discontinuation of NIVO+IPI, stratified by reason for discontinuation of NIVO+IPI, disease progression or adverse events, IMDC all risks. (f) PFS of TT after discontinuation of NIVO+IPI, stratified by TT regimens after NIVO+IPI, sunitinib or axitinib, IMDC all risks.
Figure 2.
Figure 2.
Overall survival (OS) of TT after discontinuation of nivolumab (NIVO) or nivolumab and ipilimumab combination therapy (NIVO+IPI). (a) OS of TT after discontinuation of NIVO, stratified by TTF of NIVO, with a cutoff value at 6 months. (b) OS of TT after discontinuation of NIVO, stratified by reason for discontinuation of NIVO, disease progression or adverse events. (c) OS of TT after discontinuation of NIVO, stratified by TT regimens after NIVO, sunitinib or axitinib. (d) OS of TT after discontinuation of NIVO+IPI, stratified by TTF of NIVO+IPI, with a cutoff value at 6 months, IMDC all risks. (e) OS of TT after discontinuation of NIVO+IPI, stratified by reason for discontinuation of NIVO+IPI, disease progression or adverse events, and IMDC all risks. (f) OS of TT after discontinuation of NIVO+IPI, stratified by TT regimens after NIVO+IPI, sunitinib or axitinib, IMDC all risks.
Figure 3.
Figure 3.
PFS2 of nivolumab (NIVO) or nivolumab and ipilimumab combination therapy (NIVO+IPI). (a) PFS2 of NIVO, stratified by TT regimens after NIVO, sunitinib, or axitinib. (b) PFS2 of NIVO+IPI, stratified by TT regimens after NIVO+IPI, sunitinib, or axitinib, IMDC all risks.
Figure 4.
Figure 4.
OS from first-line therapy of patients treated with nivolumab (NIVO) or nivolumab and ipilimumab combination therapy (NIVO+IPI). (a) OS from first-line therapy of patients treated with NIVO, stratified by TT regimens after NIVO, sunitinib or axitinib. (b) OS from first-line therapy of patients treated with NIVO+IPI, stratified by TT regimens after NIVO+IPI, sunitinib or axitinib, IMDC all risks.
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