Multi-centre review of systemic anti-cancer prescribing patterns and treatment drop off rates in the United Kingdom 2018-2021

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.

A multicenter real-world study reviewing systemic anticancer treatment choices and drop off rates between treatment lines for metastatic renal cell carcinoma in the United Kingdom: In the immunotherapy era

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.

LBA4 Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol

Background: Patients (pts) with high-risk M0 PCa are treated with ADT and when indicated, local radiotherapy (RT). Intensifying hormone treatment with AAP, ENZ or apalutamide continuous to progression improves outcomes of metastatic PCa but its efficacy in M0 PCa starting ADT is unknown. Methods: STAMPEDE is a multi-arm, multi-stage trial that, as part of 2 separate comparisons randomised PCa pts with M0 node positive or high-risk node negative (>1 T3/4, PSA ≥40ng/ml, Gleason 8-10 or relapsing) 1:1 to ADT (control) vs ADT with AAP (1000mg AA + 5mg P od) or ADT vs ADT with AAP + ENZ (160mg od) for 2 years (y), unless RT was omitted when treatment could be to progression. The primary end-point was metastasis-free survival (MFS, time to death or distant metastases). The sub-group of pts who received ADT +/- AAP was partially reported with metastatic pts in 2017 so one-sided type 1 error rate was set to 1.25%. All analyses were pre-specified, pooled using meta-analyses methods and stratified as described previously. Data frozen 3rd August 2021. Results: 1974 M0 pts at 113 sites in UK & Switzerland were randomised, 914 (Nov 2011 to Jan 2014) to ADT +/- AAP & 1060 (Mar 2016 to Jul 2014) to ADT +/- AAP + ENZ. Groups were well balanced: median age 68 y, range 43-86;median PSA 34 ng/ml, range 0.4-2773;Gleason 8-10, 79%;node positive 39%;planned for RT 85%. Median months to stopping AAP, 23.7 (IQR: 17.6-24.1);AAP when given with ENZ, 20.7 (IQR: 4.4-24);ENZ, 23.2 (IQR: 6.3-24). 180 MFS events occurred in the research group and 306 in the control group. AAP-based therapy improved MFS (HR 0.53, 95% CI 0.44-0.64, P=2.9×10- 11) & survival (HR 0.60, 95% CI 0.48-0.73, P=9.3×10-7): 6-y MFS from 69% to 82%, 6-y survival from 77% to 86%. Treatment effect was consistent in major subgroups and between AAP & AAP + ENZ randomisation periods (MFS HR=0.54, 95% CI 0.43-0.68;HR=0.53, 95% CI 0.39-0.71 respectively;interaction HR = 1.02, 95% CI: 0.70-1.50, p=0.908). Conclusions: 2 y of AAP-based therapy significantly improves MFS & survival of high-risk M0 PCa starting ADT and should be considered a new standard of care. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Astellas, Janssen. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Sapience;Financial Interests, Personal, Advisory Board: Orion;Financial Interests, Personal, Royalties: Janssen;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Astellas;Non-Financial Interests, Principal Investigator: Janssen;Non-Financial Interests, Advisory Role: Janssen;Non-Financial Interests, Advisory Role: AstraZeneca;Non-Financial Interests, Principal Investigator: Astellas. L.C. Brown: Financial Interests, Institutional, Research Grant, FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca. N. Clarke: Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Ferring;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Ferring;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Inst tutional, Research Grant: AstraZeneca. W. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics;Financial Interests, Personal, Invited Speaker, Speaker fee: Janssen;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker fee: Astellas;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. R. Jones: Financial Interests, Personal, Advisory Board, advisory board attendance: AstraZeneca;Financial Interests, Personal, Advisory Board, advisory board attendance: Astellas;Financial Interests, Personal, Invited Speaker, Honoraria for speaking: Astellas;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: Exelixis;Financial Interests, Personal, Advisory Board: Ipsen;Financial Interests, Personal, Invited Speaker: Ipsen;Financial Interests, Personal, Advisory Board: Bristol Myers Squipp;Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Merck Sharpe Dome;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Institutional, Other, IDMC membership: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Institutional, Other, IDMC member: Stab;Financial Interests, Personal, Advisory Board: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Janssen;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Tail;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: BioXcel;Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb;Financial Interests, Institutional, Invited Speaker: Novartis / AAA;Financial Interests, Institutional, Invited Speaker: Roche;Financial Interests, Institutional, Invited Speaker: MSK. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Advisory Board, 2018: Roche;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag;Financial Interests, Institutional, Advisory Board, 2020: Roche;Financial Interests, Institutional, Advisory Board, 2018: AAA International;Financial Interests, Institutional, Advisory Board, 2018: Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory Board, 2019: Tolero Pharmaceuticals;Financial Interests, Institutional, Advisory Board, 2020: MSD Merck Sharp & Dohme;Financial Interests, Institutional, Advisory Board, 2020: Pfizer;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Invited Speaker, 2021: DESO;Financial Interests, Institutional, Advisory Board, 2021: BMS;Financial Interests, Institutional, Advisory Board, 2021: AAA International;Financial Interests, Institutional, Advisory Board, 2021: Orion;F nancial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Personal, Invited Speaker, 2021: SAKK;Financial Interests, Institutional, Advisory Board, 2021: Bayer;Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, Other, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Personal, Invited Speaker, 2021: SAMO - IBCSG;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems;Non-Financial Interests, Advisory Role, 2019: Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. S. Chowdhury: Financial Interests, Personal, Advisory Board: Astellas;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Invited Speaker: Janssen;Financial Interests, Personal, Advisory Board: Huma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Novartis/AAA;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Remedy Bio;Financial Interests, Personal, Advisory Board: Athenex;Financial Interests, Personal, Advisory Board: Telix;Financial Interests, Personal, Advisory Board: Clovis Oncology;Financial Interests, Personal, Stocks/Shares: Curve Life;Financial Interests, Institutional, Research Grant: Clovis Oncology;Non-Financial Interests, Advisory Role, Non-compensated advice: NHS England;Non-Financial Interests, Advisory Role: NICE NHS England. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer:Sanofi;Other, support to attend meetings or advisory boards in the past: Astellas, Jaansen, Bayer. C. Parker: Financial Interests, Personal, Advisory Board, Education Steering Committee: Bayer;Financial Interests, Personal, Invited Speaker, Speaker at prostate cancer educational events: Janssen;Financial Interests, Personal, Advisory Board, Advisory board on apalutamide: Janssen;Financial Interests, Personal, Advisory Board, Advisory board: Clarity Pharmaceuticals;Financial Interests, Personal, Advisory Board, Advisory board on relugolix: Myovant;Financial Interests, Personal, Advisory Board, Advisory board: ITM Oncologics. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Janssen;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Novartis;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Pfizer;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Sanofi. M.K. Parmar: Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facili ate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Clovis;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Novartis;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.