Introduction
Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the 2011 Japanese Urological Association RCC guidelines (1,2); however, these guidelines do not address the order of administration of presently available multiple agents. The European Association of Urology guidelines recommend either sunitinib or everolimus as first-line therapy, and sorafenib or everolimus as second-line therapy, although there are several aspects that remain unknown regarding the optimal administration order and combination of the multiple molecular-targeted drugs (3). At the 2015 ASCO annual meeting, the results of a comparison test of sunitinib→everolimus vs. everolimus→sunitinib were reported, indicating that the median survival rates were 29.5 and 22.2 months, respectively, concluding that sunitinib→everolimus was more effective (4,5).
Until clinical trials determine the optimal treatment sequence, treatment individualization is required for each patient based on patient and disease characteristics. In this study, we investigated 12 cases of renal cancer in which axitinib had been administered.
Discussion
Based on our cases, axitinib demonstrated reasonable therapeutic efficacy as first- as well as second-line treatment. However, to draw a firm conclusion, more cases must be accumulated.
Procopio et al reviewed 13 cases of renal collecting duct carcinoma. Renal collecting duct carcinoma patients (median age, 57 years) comprise 3.4% of all metastatic RCC (mRCC) patients, with a median survival time of 4 months, with only 3 cases having survived 6–33 months (8–11). The disease-specific survival of our patient (case 11) was 13 months from the time of the appearance of metastases. In a study on the administration of sunitinib, axitinib, sorafenib, interferon and temsirolimus as first-line drugs in 4,736 mRCC cases, a reduction ratio of >7–8% of the tumor was associated with a relatively good prognosis (12). Moreover, in a study on the combined use of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in 153 cases of metastatic clear cell RCC (ccRCC), comparing the combined use of lenvatinib and everolimus with the use of lenvatinib alone and with the use of everolimus alone, achieved a survival of 13.1, 7.5 and 8.5 months, respectively, indicating that combination therapy was superior to single-agent treatment (13). Furthermore, in a study of 108 cases of non-ccRCC, survival with sunitinib was 8.3 months and that with everolimus 5.6 months, indicating that sunitinib was superior; however, for poor-risk RCC, survival was 4.0 and 6.1 months for sunitinib and everolimus, respectively, indicating that everolimus was better for poor-risk cases (14).
A study of the programmed cell death protein-1 (PD-1) antibodies for RCC was also conducted (15–17). The therapeutic effects of pazopanib and sunitinib in RCC cases expressing PD-1 were significantly inferior to the PD-1 low-expressing cases, and the median survival time was also shorter (18). Nivolumab (PD-1-inhibiting antibodies) was investigated in 91 cases, and it was effective in programmed death-ligand-1 (PD-L1)-positive as well as -negative cases (based on immunostaining of cancer cells). While a 71% 1-year survival was attained by both positive and negative cases, the 2-year survival rates were 64 and 48%, respectively (19). In addition, the mPFS of the cases in whom anti-PD-1 treatment had not been effective and in whom TKIs had been administered was 6.9 months, indicating that it may be safely administered (20). Immunostaining for PD-L1 was positive in 51% of spindle cell cancer cases, whereas 100% of the cases that contained a ccRCC component were positive (18). However, due to the fact that only 17% of the ccRCCs that did not contain a spindle cell carcinoma component were PD-L1 positive, there is a possibility that PD-1 antibodies are effective in spindle cell cancer, which has poor prognosis (21). A study to predict therapeutic effect based on immunostaining for PD-L1 of tumor cells has been conducted. However, cases were successfully treated irrespective of positive or negative immunostaining; thus, no conclusion was reached at that time (22). Moreover, it is considered that the more gene mutations the cancer cells harbour, the more successful the immunotherapy. Further research on immune therapy that includes PD-L1 antibodies is expected in the near future.