OCTOPUS: A retrospective, multicenter study of real-world cabozantinib treatment of patients with advanced renal cell carcinoma in France—Subgroup analyses of treatment sequences and optimization.

472 Background: Cabozantinib is an established therapy for advanced renal cell carcinoma (aRCC) in France. We evaluated real-world data from the OCTOPUS study to assess treatment sequences and explore strategies for therapeutic optimization. Methods: OCTOPUS was a real-world, retrospective, non-comparative, non-interventional study of 252 patients receiving second-line (2L) cabozantinib therapy at 26 centers in France between 2018 and 2021 (NCT05444933). Exploratory analyses of treatment sequences and endpoints including duration of treatment (DoT), progression-free survival (PFS), overall survival (OS) and disease control rate (DCR) were performed for subgroups of patients based on cabozantinib dose modifications, local treatment (radiotherapy or surgery) and receipt of third-line (3L) treatment. Results: In total, 252 patients (median age, 63.0 years; lung metastases, 63%; bone metastases, 52%) were included; 61% had prior tyrosine kinase inhibitor (TKI) therapy, and 37% received prior immunotherapy (IO). Patients who underwent local treatment or cabozantinib dose modifications exhibited longer 2L DoT and PFS than those without these interventions (Table). In total, 157 patients (62%) received 3L therapy post cabozantinib (55% nivolumab, 26% TKI), and 14 patients were still on cabozantinib at study end. Dose modification rates were higher among patients who received 3L therapy (≥1 reduction, 67% vs 55%; ≥1 interruption, 69% vs 56%). Those receiving 3L therapy demonstrated improved outcomes (Table); the median OS from 2L cabozantinib initiation in patients who received 3L treatment was 20.5 months (95% CI, 18.0–22.6). Conclusions: Cabozantinib outcomes may be enhanced with dose modifications and local treatment. These strategies may delay the need for 3L therapy in patients with oligoprogressive disease, potentially improving long-term disease control. Clinical trial information: NCT05444933 . Subgroup N (%) Median (95% CI) DoT for 2L cabo, months Median (95% CI) PFS from 2L cabo start, months DCR for 2L cabo, % (n/n) Overall population 252 (100) 7.4 (6.1–8.5) 6.9 (5.7–8.2) 76.9 (160/208) Dose modificationsNoYes 58 (23)194 (77) 2.5 (1.6–3.5)8.6 (7.6–9.9) 3.5 (2.2–5.7)7.6 (6.5–8.7) 62.5 (20/32)79.5 (140/176) Local treatment a,b NoSurgery or focal treatment c Radiotherapy 153 (61)25 (10)52 (21) 6.0 (4.6–7.6)9.6 (4.4–15.0)9.3 (7.6–13.3) 6.2 (5.3–8.2)8.0 (4.4–9.5)7.2 (5.2–10.1) 78.0 (96/123)90.1 (20/22)78.3 (36/46) 3L treatmentNoYes 95 d (38)157 (62) 4.3 (3.2–6.9)8.2 (6.9–9.6) 5.1 (3.1–7.3)8.0 (6.2–9.1) 69.7 (46/66)80.3 (114/142) a Patients may receive surgery and radiotherapy; b 41 patients had a surgery not related to aRCC; c Only surgeries or focal treatments related to aRCC are presented; d 14 patients were receiving 2L cabozantinib at study end.