Analysis of survival, toxicity and cost effectiveness in sequential treatment in patients with metastatic renal cell carcinoma

Objective: It was aimed to retrospectively evaluate the effects of stepwise treatments on overall survival in patients diagnosed with metastatic renal cell carcinoma. As a secondary aim of the study, it is aimed to determine the relationship between progression-free survival and toxicity and current treatments. It is aimed to create a perspective in terms of cost-effectiveness in anti-cancer agents used in addition. Material and Method: Fifty patients who were diagnosed between 2005 and 2020 in the Department of Medical Oncology, G.U.T.F, over the age of 18, with a documented pathological or radiological diagnosis of RCC, receiving stepwise treatment, de-novo or recurrent metastatic were retrospectively analyzed. The data of the first 3 digits were taken into account in the analysis. Patients with a second primary malignancy, over the age of 85, and with an ECOG (Eastern Cooperative Oncology Group) performance score of ≥3 were not included in the study. Data were obtained from patient archive files and hospital digital database. Results: A total of 50 patients, 41 (82%) male and 9 (18%) female, were evaluated. The mean age was 60.08±11.27 years. The number of de-novo metastatic patients was 42 (84%), and the number of recurrent metastatic patients was 8 (16%). 28 patients received IFN-α therapy. At any step, 29 subjects were sunitinib (49%), 16 subjects were pazopanib (32%), 10 subjects were axitinib (20%), 1 subjects were sorafenib (2%), 7 subjects were everolimus (14%), and 3 subjects were nivolumab (6%). took. The median OS in the population was 44 months. In the first-line treatment, PFS was 4.9 months in the TKI group and 7.1 months in the IFN-α group (p=0.840). According to the IMDC, among patients in the good/moderate risk group, the median PFS was 10.4 months in patients receiving IFN-α and 4.9 months in those receiving TKI; among the patients in the bad risk group, the median PFS was 3.5 months and 4.7 months in the IFN-α and TKI groups, respectively (p=0.788). When the median PFS times were evaluated 99 in second-line therapy, it was 7.2 months, 22 months and 13.4 months for axitinib, pazopanib, and sunitinib, respectively (p=0.013). Median PFS was 13 months in patients who received TKI in tertiary care; Median PFS was 6.2 months in patients receiving IFN-α, mTOR-i, or anti-PD-1 (p=0.149). Side effects were seen in 5 (17%) patients using IFN-α. Side effects were seen in 15 (53%) of the patients using sunitinib. Grade 3 and/or more severe side effects developed in 8 patients (28%). The most common severe adverse event was pneumonia (10%). Side effects were seen in 10 (62%) patients who took pazopanib. Grade 3 and/or more severe adverse events occurred in 5 (31%) patients. The most common severe adverse event was hepatotoxicity (18%). Considering all TKI patients, the most common side effects were hypothyroidism (16%) and diarrhea (14%). The highest rate of grade 3-4 adverse events is acute renal failure (9%). IFN-α in patients receiving three-line therapy; TKI; In the group receiving TKI, the median cost was 72 803 €, TKI; TKI; The median cost in the group receiving nivolumab was 91 984 €. Conclusion: It has been observed that targeted therapies provide PFS advantage in the poor risk group compared to OS and cytokine therapy. At the same time, these treatments are safe compared to their effectiveness; however, it has been seen that there are expensive treatments. Awareness of the renal side effects resulting from these agents is essential for safe treatment strategies, especially in those with pre-existing kidney disease. It is important to increase awareness and monitor thyroid function tests in patients continuing with TKIs. Key words: renal cell carcinoma, metastatic, cost, survival, toxicity