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(1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011–2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% (n = 125) female, 58% (n = 145) white, 18% (n = 45) black and 4% (n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% (n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% (n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC (n = 179), EGFR mutation status was known in 88% (n = 157) and mutation present in 19% (n = 34), ALK was known in 66% (n = 118) with a translocation in 10% (n = 18), ROS1 status was known in 57% (n = 102) with a translocation in 4% (n = 8), and KRAS status was known in 66% (n = 119) with a mutation in 12% (n = 22). Overall, 76% (n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5–11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients.

Purpose: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways. Methods and Materials: We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes. Results: A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point. Conclusions: To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare.

18 Background: TRITON3 (NCT02975934) is a randomized, multicenter, open-label, phase 3 study of rucaparib vs physician’s choice (docetaxel [DTX], abiraterone [ABI] or enzalutamide [ENZ]) in patients (pts) with chemotherapy-naïve mCRPC with BRCA1/2 (BRCA) or ATM alterations. It was previously reported that rucaparib significantly improved the primary endpoint of radiographic progression-free survival (rPFS) vs physician’s choice in pts with BRCA or ATM alterations. We report here the interim overall survival (OS) and also report on efficacy of rucaparib compared individually with either DTX or ABI/ENZ. Methods: Pts had disease progression after 1 prior second-generation androgen pathway inhibitor therapy in any setting and were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI or ENZ. An ordered step-down multiple comparisons procedure was used to control the overall error rate. OS was a key secondary endpoint with rPFS as the primary endpoint tested first in the BRCA subgroup, then the intent-to-treat (ITT) population. Subgroup analyses based on physician’s choice were exploratory. Results: As of August 25, 2022, 302 pts with BRCA and 103 pts with ATM alterations were randomized. OS maturity was 54% in the BRCA subgroup and 59% in the ITT population. rPFS and OS are shown. The most frequent treatment-emergent adverse event (TEAE) in the rucaparib, DTX and ABI/ENZ groups was asthenia/fatigue (61.1%, 67.6% and 57.6%, respectively). The most frequent grade ≥3 TEAE in the rucaparib, DTX and ABI/ENZ groups was anemia (23.7%), neutropenia (14.1%), and hypertension (10.2%), respectively. Conclusions: Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations. Clinical trial information: NCT02975934 . [Table: see text]

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.

Background Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for the treatment of breast cancer susceptibility genes 1 and 2 (BRCA1/2) mutant ovarian and breast cancers, and are now being evaluated in metastatic castration-resistant prostate cancer (mCRPC). Reversion mutations that restore BRCA1/2 function have been shown to be responsible for resistance to platinum-based chemotherapy and PARP inhibitors, however there is no information on the sequential use of these agents in prostate cancer. Case presentation A patient with mCRPC associated with a germline BRCA2 mutation was sequentially treated with carboplatin and the PARP inhibitor rucaparib. Genomic profiling of the available baseline tumor and progression blood samples using next-generation sequencing panel tests identified polyclonal BRCA2 reversion mutations post carboplatin treatment but prior to rucaparib treatment. A total of 12 somatic reversion mutations were detected and ranged from small indels to larger deletions of up to 387 amino acids. These alterations are all predicted to restore the BRCA2 open reading frame and potentially protein function. The patient received limited benefit while on rucaparib, likely due to these reversion mutations observed prior to treatment. Conclusions Here we report a case of a patient with prostate cancer who received a platinum agent and PARP inhibitor sequentially and in whom polyclonal BRCA2 reversion mutations were identified as the likely mechanism of acquired resistance to carboplatin and primary resistance to PARP inhibition. These findings suggest caution is warranted in sequencing these agents.

e17057 Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats approximately 8,800 patients annually and is one of the largest Comprehensive Cancer Centres in the UK. When dealing with the second wave of COVID-19, it is important to further evaluate the safety of cancer treatments whilst balancing the risks of COVID-19 infection and complications. Here, we report on the patient/tumour characteristics of those patients undergoing SACT for a urological cancer diagnosis during the first wave, so as to help establish clinical guidelines for the management of these patients in a SARS-CoV-2 epidemic. Methods: All urological cancer patients receiving at least one SACT between 1st March- 31st May 2020 (COVID-19 period) were compared to the same timeframe in 2019. SARS-CoV2 infection was defined as a positive RT-PCR test; patients with symptoms or radiological changes alone were excluded. As part of Guy’s Cancer Cohort, we collected information on demographics, and cancer type, stage, and treatment. Results: A total of 455 patients (305 prostate, 102 renal, 38 bladder, and 10 testicular) received SACT in 2020 as compared to 535 (353 prostate, 129 renal, 37 bladder, and 15 testicular) in 2019 (15% overall decline). Patient characteristics in terms of demographics were fairly comparable, with 10% female patients in 2019 and 9% in 2020; 49% aged 70+ vs 45%; and 77% in the low socio-economic category vs 78%. There was an increase in patients with stage 4 (89% vs 95% in 2020) and a slight change in distribution of SACT types (2019 vs 2020): chemotherapy (18% vs 14%), immunotherapy (7% vs 10%), biological or targeted (63% vs 66%), combination of biological/targeted (6% vs 5%), other combinations (5% vs 5%). The proportion of SACT delivered as part of radical treatment declined from 3% to 0.2% in 2020. A total of 5 patients (1%) developed COVID-19 (2 prostate, 2 renal, and 1 bladder). All were male and aged 60+; three had 2+ comorbidities. One patient was on immunotherapy and four on biological or targeted treatment. Four patients had severe pneumonia and one died of their COVID-19 (bladder cancer). Conclusions: Whilst there was a decline of number of patients receiving SACT during COVID-19, we were still able to provide a safe high-quality urological cancer SACT pathway during the peak of the COVID-19 pandemic, with very few COVID-19 positive patients. In a next step we will evaluate oncological outcomes at 6 months follow-up

Background: To understand the impact of the COVID-19 pandemic on National Health Services (NHS) cancer service delivery, care and patients, we examined the impact of changes in cancer service delivery, treatment intensity and delay by evaluating oncological outcomes of genitourinary (GU) cancer patients receiving systemic anticancer treatment (SACT) during 1st March and 8th July 2020. Methods: We used data from patients with GU cancers (i.e. prostate, urothelial, kidney and testicular) treated with SACT at Guy’s Cancer Centre during the first wave of the COVID-19 pandemic in the UK: demographics (sex, age, ethnicity, ECOG performance status (PS), comorbidities, smoking history, socio-economic status (SES)) and disease characteristics (stage, treatment type and setting, lines of treatment), as well as results from SARS-CoV-2 PCR testing. Classification of COVID-19 severity was based on the World Health Organisation (WHO) guidelines. Results: A total of 457 GU cancer patients received SACT during the study period: 68% prostate cancer, 23% renal cancer, 7% urothelial cancer, 2% testicular cancer. Mean age was 69 years (SD: 11.2). 91% were males, 82% were classified as low SES and out of the 291 patients we had ethnicity data on 199 (68%) were White British. The majority of patients had a PS of 1 and 95% of all patients had stage IV disease and hence received palliative SACT, with 58% being in the second line setting. Half of the patients received hormone therapy, 17% received chemotherapy, 20% received targeted therapy, 13% received immunotherapy (IO) and 1% received combination IO and targeted treatment. Only 5 (1%) patients tested SARS-CoV-2 positive: 2 had prostate cancer, 2 renal and 1 bladder cancer. Mean age was 66 years (SD: 5.6). They were all male, 2 White British, 1 Black African and 2 of unknown ethnicity and were all classified as low SES. Average PS was 2. Of these 5 patients 3 had at least two comorbidities (i.ehypertension, diabetes mellitus, renal impairment, frailty) and were receiving multiple medications. All had stage IV disease and received palliative SACT. 3 were on hormone therapy alone and 2 on chemotherapy. 2 of the patients presented symptoms within less than 7 days from PCR diagnosis, 1 within 7 to 14 days and 1 after 14 days. All 5 COVID-19 positive patients required hospitalization, 4 suffered severe pneumonia, 1 died from COVID-19 and 2 died from cancer related causes. In comparison, the mortality rate for the COVID-19 negative patients was 3.3%. Conclusion: Despite the impact of COVID-19 in health provision, a large number of our GU patients at Guy’s Cancer Centre safely received SACT. Our results suggest that the continuation of SACT during the COVID-19 pandemic did not increase the risk of COVID-19 in our patient cohort (SARS-CoV-2 infection rate: 1%). Of note, the infection rate was lower than observed in a similar study in our centre for gastrointestinal cancer patients (SARS-CoV-2 infection rate: 3.4%). In light of the above, decisions against SACT or SACT intensity should carefully be evaluated. Citation Format: Christina Karampera, Beth Russell, Charlotte Moss, Rushan Sylva, Kieran Palmer, Elias Pintus, Sarah Rudman, Debra Josephs, Kamarul Zaki, Mieke Van Hemelrijck, Saoirse Dolly, Deborah Enting. Real world data analysis of patients with genitourinary cancers receiving systemic anticancer treatment during the COVID-19 pandemic at Guy's Cancer Centre: A single centre retrospective study in the UK [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S09-03.

Introduction Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are commonly prescribed for metastatic castration-resistant prostate cancer (mCRPC). Data comparing their effects on patient-reported outcomes (PROs) from routine clinical practice are limited. Methods AQUARiUS (NCT02813408) is an ongoing, two-cohort, prospective, observational, non-randomised, multicentre, phase IV European study assessing the effects of AAP and ENZ on PROs in 211 patients with mCRPC over 12 months. Patients receive AAP or ENZ per routine clinical practice. Data on cognition, fatigue, pain and health-related quality of life are measured using the Functional Assessment of Cancer Therapy-Cognitive Function, Brief Fatigue Inventory-Short Form, Brief Pain Inventory-Short Form and European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaires, respectively. Results This 3-month analysis was conducted in 105 patients; 46 received AAP and 59 received ENZ. There were statistically significant differences in mean change from baseline favouring AAP over ENZ at months 1, 2 and 3 for perceived cognitive impairments and cognitive functioning. At each time-point, ENZ-treated patients had a significantly higher risk of experiencing clinically meaningful worsening in perceived cognitive impairments versus those receiving AAP. Statistically significant differences in mean change from baseline favouring AAP over ENZ were seen for usual level of fatigue and fatigue interference at months 2 and 3 and for current fatigue and worse level of fatigue at month 3. Differences favouring AAP versus ENZ were seen for the fatigue scale of the QLQ-C30 questionnaire (months 1 and 3). There was a significantly higher risk of clinically meaningful worsening in usual level of fatigue with ENZ versus AAP at month 3. No significant differences between cohorts were observed for pain (BPI-SF) at any time-point. Conclusion This analysis suggests more favourable outcomes with AAP versus ENZ for cognition and fatigue in the first 3 months of treatment initiation for mCRPC. These findings require confirmation from future analyses of data from AQUARiUS from a larger number of patients with a longer follow-up period.

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.

5058Background: AQUARiUS is an ongoing study of PROs and medical resource use in chemotherapy-naive pts with mCRPC newly initiated on AAP or ENZ in a real-world setting. Initial 3-month (mo) subset...