Navani Vishal, Wells J Connor, Boyne Devon J, Cheung Winson Y, Brenner Darren M, McGregor Bradley A, Labaki Chris, Schmidt Andrew L, McKay Rana R, Meza Luis, Pal Sumanta K, Donskov Frede, Beuselinck Benoit, Otiato Maxwell, Ludwig Lisa, Powles Thomas, Szabados Bernadett E, Choueiri Toni K, Heng Daniel Y C
Tom Baker Cancer Centre, Calgary, Canada.
BC Cancer Agency, Vancouver, Canada.
Clin Genitourin Cancer. 2023 Feb;21(1):106.e1-106.e8. doi: 10.1016/j.clgc.2022.07.008. Epub 2022 Jul 21.
There are limited data evaluating the activity of cabozantinib (CABO) as second line (2L) therapy post standard of care ipilimumab-nivolumab (IPI-NIVO) or immuno-oncology(IO)/vascular endothelial growth factor inhibitor (VEGFi) combinations (IOVE).
Using the IMDC database, we sought to identify the objective response rate, time to treatment failure (TTF) and overall survival (OS) of 2L CABO after IPI-NIVO, IOVE combinations, pazopanib or sunitinib (PAZ/SUN) or other first line (1L) therapies. Multivariable Cox regression, adjusted for underlying differences in IMDC groups, was used to compare differences in OS for 2L CABO based on preceding therapy.
Three hundred and forty-six patients received 2L CABO (78 post IPI NIVO, 46 post IOVE, 161 post PAZ/SUN, 61 post Other). Of the entire cohort, 12.6%, 62.6%, and 24.8% were IMDC favourable, intermediate, and poor risk, respectively. Patients that received 1L IPI-NIVO had a median OS of 21.4 (95% CI, 12.1 - NE [Not evaluable]) months compared to 15.7 (95% CI, 9.3 - NE) months in 1L IOVE and 20.7 (95% CI, 15.6 - 35.6) months in 1L PAZ/SUN, P = .28. Median TTF from the initiation of 2L CABO in the overall population was 7.6 (95% CI, 6.6 - 9.0) months. We were unable to detect a significant difference in 2L CABO OS based on type of 1L therapy received: 1L IPI-NIVO (reference group) vs. 1L IOVE HR 1.73 (95% CI, 0.83 - 3.62 P = .14), 1L PAZ/SUN 1.16 (95% CI, 0.67 - 2.00 P = .60), however given the retrospective observational nature of this work a lack of sufficient power may contribute to this.
In a large real world dataset, we identified clinically meaningful activity of 2L CABO after all evaluated contemporary 1L therapies, irrespective of whether the 1L regimen included a VEGFi. These are real world benchmarks with which to counsel our patients.
评估卡博替尼（CABO）作为标准治疗药物伊匹单抗-纳武单抗（IPI-NIVO）或免疫肿瘤学（IO）/血管内皮生长因子抑制剂（VEGFi）联合治疗（IOVE）后的二线（2L）治疗活性的数据有限。
利用IMDC数据库，我们试图确定IPI-NIVO、IOVE联合治疗、帕唑帕尼或舒尼替尼（PAZ/SUN）或其他一线（1L）治疗后2L CABO的客观缓解率、治疗失败时间（TTF）和总生存期（OS）。使用多变量Cox回归，并根据IMDC组的潜在差异进行调整，以比较基于先前治疗的2L CABO的OS差异。
346例患者接受了2L CABO治疗（IPI-NIVO后78例，IOVE后46例，PAZ/SUN后161例，其他后61例）。在整个队列中，IMDC风险低、中、高的患者分别占12.6%、62.6%和24.8%。接受1L IPI-NIVO治疗的患者的中位OS为21.4（95%CI，12.1-NE[不可评估]）个月，而接受1L IOVE治疗的患者为15.7（95%CI，9.3-NE）个月，接受1L PAZ/SUN治疗的患者为20.7（95%CI，15.6-35.6）个月，P=0.28。总体人群中从开始2L CABO治疗起的中位TTF为7.6（95%CI，6.6-9.0）个月。我们无法根据接受的1L治疗类型检测到2L CABO OS的显著差异：1L IPI-NIVO（参照组）与1L IOVE相比，HR为1.73（95%CI，0.83-3.62，P=0.14），1L PAZ/SUN为1.16（95%CI，0.67-2.00，P=0.60），然而鉴于这项研究的回顾性观察性质，缺乏足够的检验效能可能导致了这一结果。
在一个大型真实世界数据集中，我们确定了在所有评估的当代1L治疗后2L CABO具有临床意义的活性，无论1L治疗方案是否包含VEGFi。这些是用于为我们的患者提供咨询的真实世界基准。
