ABSTRACT
Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over recent years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. There is ongoing discussion amongst oncology professionals about how best to optimise treatments in terms of sequencing to maximise the potential number of lines or to give the best treatments first. A previous south-west UK audit was completed in 2021 reviewing the drop off rates across 5 UK sites identifying that 69% of patients were able to receive second line therapy and 34% were able to receive third line therapy. Method(s): In this study we conducted retrospective analysis of all patients who commenced treatment with SACT for mRCC between 1st January 2018 and 30th June 2021 in 18 centres across the 4 nations of the United Kingdom. All NHS reimbursed treatment options including the COVID interim treatment guideline options were included. Patients who received SACT as part of a clinical trial were also included. Patients who continued on their respective lines of treatment were censored. We also identified patients who had been on a period of active surveillance before staring SACT in this cohort. Result(s): 1549 patients (71% male: 29% female) were included. IMDC subgroup patients included 21.6%favourable, 52.3% intermediate, 25.1%poor and 1% unavailable. 9.1% of patients had been on active surveillance before starting SACT - defined as a period of longer than 3 months from mRCC diagnosis to starting SACT. Of those patients that started SACT 60.5% of eligible patients had 2nd line therapy, 25.3% had 3rd line, 7.2% received 4th line therapy and only 1% had 5th line therapy. In the 1st line setting 58.9% received single agent VEGF TKI, 24.5% received combination ipilimumab and nivolumab (IO-IO) immunotherapy, 14 % received IO/ VEGF TKI combination and 2.6% received other/trial treatment. The single agent VEGF TKI ratio for 1st line SACT declined year by year with rising IO-IO and IO/VEGF TKI combination ratios seen. In the secondand third-line settings cabozantinib (33.2% 2nd line and 44.4% 3rd line) and nivolumab (32.8% 2nd line and 22.6% 3rd line) were the most common options. Disease progression or death was the most common cause of SACT discontinuation amounting to 57.4%, 62.5% and 79% of SACT cessation in the 1st, 2nd and 3rd lines respectively. Treatment toxicity SACT discontinuation rates were 22.8%, 21.4% and 10.9% for 1st, 2nd and 3rd lines respectively. Conclusion(s): These results suggest that with more treatment options available, including combination/immunotherapy therapies, more patients are able to receive second- and third-line therapies. That said there remains significant drop off rates mostly driven by disease progression that would support the use of our most effective therapies in the upfront setting.
ABSTRACT
Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved over the last few years with several systemic anti-cancer therapies (SACT) licensed across different lines of treatment. A previous real world study in the UK had demonstrated a significant attrition rate between each line of therapy suggesting less than half of patients who received first line SACT then received second line therapy and less than a fifth of first line SACT patients reach third line. Methods: We conducted a retrospective analysis of all patients treated between January 2018 and end of June 2021 to see if advancement in treatment options had impacted on the drop-off rates. Data was collected from 5 UK sites. Patients were identified from electronic SACT database. All reimbursed treatment options including the COVID interim treatment guidelines options were included. Patients who received SACT as part of a clinical trial were also included. Patients who remained on the respective lines of treatment were censored. Results: Data for 515 patients (372 male: 143 female) who received first-line SACT for mRCC were included in the analyses. IMDC prognostic groups were 103 favourable, 236 intermediate, 127 poor (49 not available). On progression 69% of patients were able to receive second-line therapy and 34% were able to receive third-line therapy. Of the 515 first-line therapies, 24% of patients received frontline ipilimumab and nivolumab, 10% received TKI and IO combination and 63% received single agent VEGF TKI. Second-line nivolumab or cabozantinib (43% and 40% respectively) were the most commonly prescribed options. Third-line cabozantinib 61% and nivolumab 16% remain the most used options. Across all lines of therapy progressive disease was the primary reason for discontinuation. 5% switched treatment due to toxicity. Conclusions: These results suggest that, with more treatment options available, including combination/ immunotherapy therapies, more patients are able to receive second and third-line therapies. Despite this, nearly one third of patients only receive one line of treatment which highlights the need to deliver the most efficacious treatments first to optimise patient outcomes. Moreover, single agent TKI was the most commonly used first-line SACT despite advances in the management pathway. Data analysing the impact of COVID on treatment selection will be presented.