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Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (nivolumab plus ipilimumab, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received nivolumab plus ipilimumab had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs than sunitinib.

Supplementary Data from Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial

Advanced Renal Cell Carcinoma; Adverse Events; Nivolumab Carcinoma de células renales avanzado; Eventos adversos; Nivolumab Carcinoma de cèl·lules renals avançat; Esdeveniments adversos; Nivolumab Background and Objectives Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC. Methods Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms. Results Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs. Conclusions Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period.

263 Background: IO-based combination therapies have improved clinical outcomes in aRCC; several are approved for first-line use. AEs can significantly impact quality of life, and IO therapy is associated with AEs that differ from prior standard treatment toxicities. PROMs capture health status directly from patients and often include the symptoms and severity of AEs. Our aim was to assess the extent to which the PROMs used in pivotal trials covered the most common AEs associated with IO combinations. Methods: This was a review of data from four phase 3, randomized, open-label studies of IO-based combinations in previously untreated advanced/metastatic clear-cell RCC (CheckMate 214, CheckMate 9ER, KEYNOTE-426, CLEAR [KEYNOTE-581]). The 10 most common all-grade, all-cause AEs (%) and the PROMs used in each trial were identified. The inclusion of the most common AEs in the PROMs was explored descriptively. Results: The most common AEs and their frequencies varied among the different combination regimens. There was also variation across trials in the PROMs used. Capture of the most common AEs by the PROMs used in each study is summarized in the Table. Conclusions: Current PROMs used in clinical trials of IO combinations for aRCC tend to capture more of the common AEs for IO-IO vs IO-tyrosine kinase inhibitor regimens. PROMs that reflect the unique AE profiles of IO therapies, especially from the patient perspective, may be needed for future trials.[Table: see text]

This large-scale, US-based study characterized real-world treatment patterns and clinical outcomes in patients with advanced or metastatic urothelial carcinoma (aUC).This retrospective cohort analysis included patients with stage IV or node-positive aUC between January 1, 2011, and August 31, 2020, from an electronic health record-derived, de-identified database (Flatiron Health). Baseline characteristics and treatment patterns were assessed by first-line (1L) systemic treatment received and cisplatin eligibility status. Overall survival (OS) and progression-free survival (PFS) were evaluated.Of 8,183 patients included, 5,855 (71.6%) received systemic 1L therapy and 2,328 (28.4%) did not. Median (range) follow-up from aUC diagnosis was 9.7 (0.2-116.6) months. Of patients who received 1L systemic therapy, 30.1% were cisplatin-eligible, 39.2% were cisplatin-ineligible, 10.5% did not receive cisplatin despite qualifying ECOG PS and renal function, and cisplatin eligibility was unknown in 20.2%. Of those treated, 74.8% received 1L chemotherapy and 23.0% received 1L immuno-oncology-based monotherapy. Median OS (95% CI) was 14.5 (14.0-15.2) months in patients who received 1L systemic therapy and 6.8 (6.2-7.3) months in those who did not. Of those treated, cisplatin-ineligible patients had worse OS and PFS outcomes vs. other subgroups. Among cisplatin-ineligible patients, 1L immuno-oncology monotherapy (n = 865) was associated with worse OS and PFS outcomes than 1L chemotherapy (n = 1,369).More than 25% of aUC patients did not receive 1L systemic therapy; of patients who were treated, most received chemotherapy, with less than 25% receiving immuno-oncology-based monotherapy. Overall, these results highlight the substantial unmet need in this population, specifically among cisplatin-ineligible patients.

311 Background: The immuno-oncology (IO) therapy combination nivolumab + ipilimumab, and the IO-tyrosine kinase inhibitor (TKI) combination pembrolizumab + axitinib, received US FDA approvals in 2018 and 2019, respectively, as first-line (1L) therapy for advanced renal cell carcinoma (aRCC). We examined physician perceptions of concerns about and barriers to 1L treatment by class of regimen (IO-IO, IO-TKI, and single-agent TKI [SA-TKI]) in the United States. Methods: US-based oncologists treating ≥ 5 aRCC patients in the prior 12 months were identified from the Cardinal Health network, a community of > 800 oncologists. Physicians were surveyed about concerns in prescribing and barriers to treating by class (scale of 1–5; 1 = no concern/not a barrier, 5 = most concerning/major barrier); mean scores are reported. Adverse events (AEs) of concern were selected from a prespecified list and respondents rank-ordered from most to least concerning by class. Physicians were also asked to gauge affordability and to rank-order 13 characteristics to identify key factors in prescribing preference. The impact of COVID-19 on aRCC care in practice was also assessed. Results: A total of 49 providers (84% community, 16% academic) treating a median of 20 (IQR 14–30) aRCC patients from across the United States participated. For IO-IO, the top 3 concerns in prescribing were AEs (4.3), patient out-of-pocket costs (OOP; 3.7), and unexpected late AEs (3.6), whereas patient OOP (4.3), AEs (4.1), and patient adherence (3.9) were of most concern for IO-TKI. For SA-TKIs, the top 3 concerns were patient adherence (3.9), patient OOP (3.9), and AEs (3.6). High patient OOP and impact on quality of life were the top 2 barriers in using IO-TKI therapy. The most concerning AEs were colitis, pneumonitis, and hypertension for IO-IO or IO-TKI, and diarrhea, fatigue, hand-foot syndrome, and hypertension for SA-TKI. Overall survival (OS), progression-free survival (PFS), and complete response (CR) were ranked 1st, 2nd, and 3rd factors in prescribing preferences while patient compliance, patient preference, and practice reimbursement ranked 11th, 12th, and 13th. Patient OOP and drug acquisition costs (DAC) were the most important factors when considering the affordability of treatment, with the perception that IO-IO was the most expensive among the classes of therapy. The overall impact of COVID-19 on caring for aRCC patients was very limited, with a moderate increased use of telemedicine and a slight impact on the timing and number of routine care visits. Conclusions: OS, PFS, and CR ranked highest among the most important factors influencing selection of 1L treatment for aRCC. Factors of concern and barriers varied by class of treatment, with patient adherence and OOP affecting use of TKI or IO-TKI therapies, and AEs affecting the use of IO-based therapy. This study revealed perceptions of high patient OOP and DAC of IO-IO therapy, in contrast to our expectations.