Efficacy and safety of subsequent molecular targeted therapy after immuno-checkpoint therapy, retrospective study of Japanese patients with metastatic renal cell carcinoma (AFTER I-O study)

Tomita, Yoshihiko; Kimura, Go; Fukasawa, Satoshi; Numakura, Kazuyuki; Sugiyama, Yutaka; Yamana, K.; Naito, Sei; Kabu, Koki; Tajima, Yuko; Oya, Mototsugu

doi:10.1093/jjco/hyaa266

Cited by 14 publications

(21 citation statements)

References 44 publications

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“…Most of the outcomes of subsequent therapy observed in pivotal clinical trials are insufficient, and long-term follow-ups and observational studies of subsequent therapy in real-world settings are needed for decision-making regarding treatment strategies. Consistent with previous reports on the outcomes of subsequent therapy after NIVO or immuno-oncology (I-O) combination therapy ( 5–21 ), we have also reported favorable anti-tumor activity of TT after the discontinuation of NIVO or NIVO+IPI in mRCC patients in Japanese real-world settings in the ‘AFTER I-O study’ ( 22 ).…”

Section: Introductionsupporting

confidence: 91%

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

Tomita

Kimura

Fukasawa

et al. 2021

Japanese Journal of Clinical Oncology

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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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Section: Introductionsupporting

confidence: 91%

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

Tomita

Kimura

Fukasawa

et al. 2021

Japanese Journal of Clinical Oncology

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“…Second‐line TKI treatment after failure of first‐line nivolumab and ipilimumab showed an ORR of 36% and a median PFS of 7–8 months 24 . The ORR of TKI after nivolumab was 27% with a median PFS of 8.9 months in a separate retrospective study 25 . The efficacy of salvage ICI/TKI in ICI‐pretreated patients was reported in a Phase II study, which demonstrated an ORR of 55.8% and a median PFS of 12.2 months by pembrolizumab and lenvatinib 26 .…”

Section: Discussionmentioning

confidence: 80%

“… 24 The ORR of TKI after nivolumab was 27% with a median PFS of 8.9 months in a separate retrospective study. 25 The efficacy of salvage ICI/TKI in ICI‐pretreated patients was reported in a Phase II study, which demonstrated an ORR of 55.8% and a median PFS of 12.2 months by pembrolizumab and lenvatinib. 26 Although some individual patients might achieve relatively longer PFS, both ORR and PFS seem to fall short by salvage nivolumab and ipilimumab therapy, compared with TKI‐incorporated therapies.…”

Section: Discussionmentioning

confidence: 99%

Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy in metastatic renal cell carcinoma: A meta‐analysis

Yang

Mori

et al. 2022

Cancer Medicine

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Background: Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy is frequently used off-label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available to guide such therapy. We performed a meta-analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab. Methods:We conducted a systematic review in accordance with PRISMA.Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review.The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values.Results: A total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09-0.21) and median progressionfree survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9-10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti-PD-1/PD-L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19-0.33). There were no new safety signals observed in this study. Conclusion:Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti-PD-1/PD-L1 therapy.

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“…Furthermore, patients after NIVO + IPI are naïve for VEGFR-TKIs. Tomita et al [19] reported that the ORR and median PFS of VEGFR-TKIs after NIVO + IPI were 32% and 16.3 months, respectively. Auvray et al [20] reported that the median PFS of sunitinib after NIVO + IPI was 11 months.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Alternative Treatment with Every-Other-Day Dosing of Sunitinib for Metastatic Renal Cell Carcinoma: Extended Follow-Up

et al. 2022

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Introduction: We investigated the efficacy and safety of every-other-day dosing of sunitinib for the treatment of metastatic renal cell carcinoma (mRCC) with extended follow-up and the impact of immune checkpoint inhibitor (ICI) drugs. Methods: Thirty-two patients received standard dosing treatment (standard group), and 32 received every-other-day treatment (experimental group). Efficacy endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate. We also analyzed the clinical course of patients treated with nivolumab after sunitinib. Results: The minimum follow-up was 42 months. Median PFS and OS were significantly longer in the experimental group compared with the standard group (27.6 vs. 6.2 and 87.1 vs. 24.6 months, respectively). The incidence of dose interruption of sunitinib caused by adverse events was significantly lower in the experimental group than in the standard group (28.1% vs. 56.3%, p = 0.042). Multivariate analysis showed that every-other-day dosing was a significant independent prognostic factor (p = 0.038), although nivolumab use was not (p = 0.232). Twelve patients were treated with nivolumab after sunitinib, and patients who did not respond to nivolumab tended to respond to pretreatment sunitinib for a long period. Discussion/Conclusion: Long-term follow-up confirmed the efficacy and safety of every-other-day dosing of sunitinib for mRCC patients in the ICI era.

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Efficacy and safety of subsequent molecular targeted therapy after immuno-checkpoint therapy, retrospective study of Japanese patients with metastatic renal cell carcinoma (AFTER I-O study)

Cited by 14 publications

References 44 publications

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

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

Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy in metastatic renal cell carcinoma: A meta‐analysis

Alternative Treatment with Every-Other-Day Dosing of Sunitinib for Metastatic Renal Cell Carcinoma: Extended Follow-Up

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