Cancer Medicine (Aug 2023)

Primary resistance to nivolumab plus ipilimumab therapy in patients with metastatic renal cell carcinoma

  • Kazuyuki Numakura,
  • Yuya Sekine,
  • Shingo Hatakeyama,
  • Yumina Muto,
  • Ryuta Sobu,
  • Mizuki Kobayashi,
  • Hajime Sasagawa,
  • Soki Kashima,
  • Ryohei Yamamto,
  • Taketoshi Nara,
  • Hideo Akashi,
  • Ryuji Tabata,
  • Satoshi Sato,
  • Mitsuru Saito,
  • Shintaro Narita,
  • Chikara Ohyama,
  • Tomonori Habuchi

DOI
https://doi.org/10.1002/cam4.6306
Journal volume & issue
Vol. 12, no. 16
pp. 16837 – 16845

Abstract

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Abstract Background Nivolumab plus ipilimumab (NIVO+IPI) is the first‐line treatment for patients with metastatic renal cell carcinoma (mRCC). Approximately 40% of patients achieve a durable response; however, 20% develop primary resistant disease (PRD) to NIVO+IPI, about which little is known in patients with mRCC. Therefore, this investigation aimed to evaluate the clinical implication of PRD in patients with mRCC to select better candidates in whom NIVO+IPI can be initiated as first‐line therapy. Methods This multi‐institutional retrospective cohort study used data collected between August 2015 and January 2023. In total, 120 patients with mRCC treated with NIVO+IPI were eligible. Associations between immune‐related adverse events and progression‐free survival, overall survival (OS), and objective response rate were analyzed. The relationship between other clinical factors and outcomes was also evaluated. Results The median observation period was 16 months (interquartile range, 5–27). The median age at NIVO+IPI initiation was 68 years in the male‐dominant population (n = 86, 71.7%), and most patients had clear cell histology (n = 104, 86.7%). PRD was recorded in 26 (23.4%) of 111 investigated patients during NIVO+IPI therapy. Patients who experienced PRD showed worse OS (hazard ratio: 4.525, 95% confidence interval [CI]: 2.315–8.850, p < 0.001). Multivariable analysis showed that lymph node metastasis (LNM) (odds ratio: 4.274, 95% CI: 1.075–16.949, p = 0.039) was an independent risk factor for PRD. Conclusions PRD was strongly correlated with worse survival rates. LNM was independently associated with PRD in patients with mRCC receiving NIVO+IPI as first‐line therapy and might indicate that a candidate will not benefit from NIVO+IPI.

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