Nivolumab plus ipilimumab (IO-IO) provides durable clinical benefit in metastatic renal cell carcinoma (mRCC), yet long-term real-world data focusing on progression-free and treatment-free (PF-TF) survival remain limited. This study aimed to evaluate the long-term outcomes of IO-IO with a particular focus on the frequency and clinical characteristics of PF-TF.
We retrospectively analyzed 63 patients with mRCC treated with first-line IO-IO across eight institutions with a minimum potential follow-up of five years. Progression-free survival (PFS), PFS2, and overall survival (OS) were assessed. PF-TF was defined as absence of disease progression and any cancer-directed therapy at the five-year landmark. Clinical and treatment-related factors were compared between patients with and without PF-TF.
The median PFS, PFS2, and OS were 7.5 (95% confidence interval [CI], 5.1-13.3), 26.2 (95% CI, 13.6-46.6), and 47.4 months (95% CI, 29.3-not reached), respectively. At 5 years, 11 patients (17%) achieved PF-TF. Baseline characteristics, IMDC risk classification, and peripheral blood biomarkers were not predictive of PF-TF. PF-TF was associated with the absence of bone metastases, presence of lymph node metastases, and occurrence of immune-related adverse events (irAEs), as well as the delayed onset of irAEs. No PF-TF patients required corticosteroid pulse therapy, and durable PF-TF was observed even after early treatment discontinuation due to adverse events.
IO-IO demonstrated sustained long-term efficacy in real-world practice, with a subset achieving durable PF-TF. These findings highlight IO-IO as a strategy capable of providing long-term disease control with reduced treatment burden in selected patients with mRCC.
Cancers. 2026 Apr 21*** epublish ***
Hiroaki Ikoma, Shuzo Hamamoto, Yoshihiko Tasaki, Misato Tomita, Kengo Kawase, Hiroko Suzuki, Yusuke Noda, Masayuki Usami, Yohei Tsubouchi, Ryuga Kato, Takuya Sakata, Yoshihisa Mimura, Toshiharu Morikawa, Takashi Nagai, Rei Unno, Toshiki Etani, Taku Naiki, Yosuke Sugiyama, Takahiro Yasui
Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan., Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan., Department of Urology, Kainan Hospital, 396 Minamihonda, Maegasu-cho, Yatomi, Aichi 498-8502, Japan., Department of Urology, Anjo Kosei Hospital, 28 Higashihirokute, Anjo-cho, Anjo, Aichi 446-8602, Japan., Department of Urology, Toyota Kosei Hospital, 1-500 Ibobara, Josui-cho, Toyota, Aichi 470-0396, Japan., Department of Urology, Konan Kosei Hospital, 137 Omatsubara, Takaya-cho, Konan, Aichi 483-8704, Japan., Department of Urology, Nagoya Tokushukai General Hospital, 2-52 Takakuraji-cho Kita, Kasugai, Aichi 487-0013, Japan., Department of Urology, Gamagori City General Hospital, 1-1 Goshonishi-machi, Goi-cho, Gamagori, Aichi 443-8501, Japan.