Abstract 1467P
Background
There are no approved neoadjuvant treatments for localised renal cell carcinoma (RCC). Comparative data on primary tumour responses in patients treated for metastatic RCC (mRCC) may help guide selection of treatments for future prospective neoadjuvant studies.
Methods
This was a retrospective study of patients with treatment-naïve mRCC with primary tumour in situ, treated at St Bartholomew’s Hospital (London, UK) between Jan 2015 and Jan 2022. Treatments studied were either immune checkpoint inhibitors (IO only), a VEGF-directed tyrosine kinase inhibitor (TKI only), or a combination thereof (IO + TKI). Size of the primary tumour was measured serially on baseline and subsequent restaging scans using RECIST 1.1 criteria, until progression, death, or cytoreductive nephrectomy. Additionally, overall survival (OS) and progression-free survival (PFS) for each group were assessed by Kaplan-Meier analysis.
Results
Overall, 60 patients were included (n = 28 for TKI only, n = 20 for IO only, n = 12 for IO + TKI). Baseline characteristics, including baseline primary tumour sizes, were similar (Table). Table: 1467P
Baseline characteristics of the three treatment groups
| Baseline characteristics* | TKI only n = 28 | IO only n = 20 | IO + TKI n = 12 |
| Age (years) | 64 ± 13.9 | 59 ± 9.4 | 61 ± 8.6 |
| Male sex | 21 (75%) | 15 (75%) | 9 (67%) |
| Karnofsky performance status score | 90 ± 11.4 | 80 ± 9.2 | 85 ± 7.5 |
| International mRCC database consortium score | 2 ± 1.0 | 3 ± 1.4 | 2 ± 0.8 |
| Baseline primary tumour size (mm) | 85.5 ± 37.7 | 88.5 ± 32.8 | 97.0 ± 23.1 |
*Median ± standard deviation for continuous variables; n (%) for categorical variables.
Median best response in the primary tumour was -11.1% with TKI only, +6.0% with IO only, and -23.0% with IO + TKI, with median time to best response in the primary tumour of 3.2 months, 2.9 months and 6.2 months respectively. In the IO + TKI group, 42% of patients achieved 30% reduction in size of the primary tumour, compared to 25% for TKI only and 20% for IO only. PFS was significantly greater with IO + TKI compared to IO only (hazard ratio (HR) 0.21 [95% confidence interval (CI) 0.09 - 0.48], p <0.01) or TKI only (HR 0.42 [95% CI 0.19 - 0.90], p = 0.03). OS was also significantly greater with IO + TKI compared to IO only (HR 0.35 [95% CI 0.13 - 0.93], p = 0.04) or TKI only (HR 0.41 [95% CI 0.18 - 0.95], p = 0.04).
Conclusions
In this retrospective study, patients with mRCC and primary tumour in situ receiving front-line IO + TKI had the greatest reduction in primary tumour size, warranting further prospective evaluation in the neoadjuvant setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers-Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd.; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers-Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. B.E. Szabados: Financial Interests, Personal, Other, travel funding: Roche/Genentech; Financial Interests, Personal, Invited Speaker: MSD, Pfizer; Financial Interests, Personal, Expert Testimony: Ellipses, Ipsen; Financial Interests, Personal, Advisory Board: Merck KGaA. All other authors have declared no conflicts of interest.