The advent of tyrosine kinase and immune checkpoint inhibitors have significantly changed and improved the management and prognosis of various malignancies, including advanced/ metastatic renal cell carcinoma (mRCC). Based on the positive results of the JAVELIN Renal 101 trial, 1 the combination of avelumab and axitinib was approved as a first-line systemic treatment for mRCC in Japan (December 2019). Although 4 years passed since the approval, several clinical questions still remain unanswered. One of them is the effectiveness and tolerability of first-line avelumab plus axitinib in a real-world setting. A recent multicenter, retrospective, observational study named "J-DART" by Kato et al. published in Int J Urol demonstrated the outcomes of the real-world cohort and were comparable with those of the JAVELIN Renal 101 trial. 2 The endpoints in J-DART included objective response rate, progression-free survival per investigator assessment, and time until treatment discontinuation.Developing standards of care for patients who do not meet trial eligibility criteria is significant unmet medical needs. The trial-ineligible subsets generally include those with poor performance status, poor organ function, and non-clear-cell pathology. Nemoto et al. demonstrated that the efficacy and safety of immune checkpoint inhibitor-based combination therapy in trial-ineligible patients was non-inferior compared with those of trial-eligible patients with mRCC. 3 However, only few patients received avelumab plus axitinib in the retrospective cohort. Differences in patient backgrounds between JAVELIN Renal 101 and J-DART is of particular interest. Although the JAVELIN Renal 101 trial only enrolled patients with clear cell RCC, the J-DART study patients included 81% clear cell RCC, 2.1% papillary RCC, and 14.6% of other histopathology RCC cases. Developing standards of care for non-clear cell RCC has been significant unmet medical needs. Recently, the results of a single-arm, multicenter, phase 2 trial KEYNOTE-B61 has been published, demonstrating durable antitumor activity and safety of firstline pembrolizumab plus lenvatinib for patients with nonclear cell mRCC. 4 Results of this trial support using pembrolizumab plus lenvatinib as a first-line treatment option for these patients. This article by Kato et al. published in Int J Urol did not focus on treatment outcomes of non-clear cell mRCC. We are hopeful that we will obtain evidence regarding real-world outcomes of using avelumab and axitinib for the trial-unfit patients with mRCC in the near future.