Background The role of simulation to develop skills around managing complex palliative care emergencies has already been established in training post-graduate doctors. Following several palliative care emergencies on a busy oncology ward, a simulation afternoon was formulated with a focus on consultant-led simulation. The session utilised a trust wide training afternoon which released departments from clinical commitments. Methods Three simulations were developed, the topics inspired by PALL-SIM-IMT by NEPRA. Scenarios were re-written to formalise a role for an oncology consultant. The topics included: status epilepticus; opiate toxicity that required careful naloxone administration; and a catastrophic bleed from a head and neck tumour. Focus was on identification of the situation, clinical judgement, application of knowledge and clinical leadership. The half-day session was hosted at the local hospice's simulation suite. It was attended by 40 people, predominantly oncology consultants with a smaller number of oncology registrars and ward nurses. Only a small proportion of attendees participated in the simulations themselves. The simulations were livestreamed to larger conference room. A member of the faculty remained with the audience and provided a running commentary to stimulate learning and discussion. Each simulation was followed by a debrief and short presentation. Results Formal feedback was collected. Attendees were asked to score each scenario with an average score of 9.32/10 for overall experience of the session and 9.21/10 that simulation was a helpful and efficient way of sharing experiences and learning new points. Following on from the session there has been continued positive feedback particularly when the scenarios have clinically occurred. Conclusion The session was able to demonstrate that palliative care simulations can be applied to other specialties and that simulation itself is well received by consultants, including when not all participants undertake the simulation itself.

Aims: In July 2022, NICE updated the guidelines on the management of melanoma by lowering the number of follow-up appointments and sentinel lymph node biopsy (SLNB) but increasing the number of scans. This study aims to evaluate the implications of executing the new guidelines in terms of cost-effectiveness and personnel. Methods: All patients newly diagnosed with melanoma in 2019 at a regional skin cancer specialist center were reviewed. Data were analyzed for their journey on an idealized pathway modeled over a 5-year follow-up period when adhering to both the previous and new guidelines. Differences in the management of melanoma were elucidated by comparing these changes. The cost was quantified on a perpatient basis and the financial implication on each department was considered. Results: One hundred and ten patients were diagnosed with melanoma in 2019, stages I-III. The changes ease the burden on plastic surgery and dermatology; however, increased pressure is faced by radiologists and histopathologists. An overall cost benefit of & POUND;141.85 perpatient was calculated, resulting in a decrease of 1.22 hospital visits on average and an increase in the time spent there (19.55 min). The additional expenses of implementing the new guidelines due to the added BRAF tests, CT, and ultrasound scans are outweighed by savings from the reduction in follow-up appointments and SLNB. Conclusion: The focus has shifted to less invasive procedures for lower melanoma stages and fewer follow-up appointments, at the expense of more genetic testing and imaging. This paper serves as a useful baseline for other centers to plan their service provision and resource allocation to adhere to the updated guidelines.Crown Copyright & COPY; 2023 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PURPOSE A DNA repair deficiency (DRD) phenotype exists within a subset of metastatic urothelial carcinomas (mUC) predicting benefit from platinum-based chemotherapy. We tested switch maintenance therapy with the poly ADP-ribose polymerase inhibitor rucaparib, following chemotherapy, for DRD biomarker–positive mUC. METHODS DRD biomarker–positive mUC patients, within 10 weeks of chemotherapy, and without cancer progression, were randomly assigned (1:1) to maintenance rucaparib 600 mg twice a day orally, or placebo, until disease progression. The primary end point was progression-free survival (PFS). Statistical analysis targeted a hazard ratio of 0.5 with a 20% one-sided α for this signal-seeking trial. PFS (RECIST 1.1) was compared between trial arms, by intention to treat, within a Cox model. RESULTS Out of 248 patients, 74 (29.8%) were DRD biomarker–positive and 40 were randomly assigned. A total of 12 (60%) and 20 (100%) PFS events occurred in the rucaparib and placebo arms, respectively (median follow-up was 94.6 weeks in those still alive). Median PFS was 35.3 weeks (80% CI, 11.7 to 35.6) with rucaparib and 15.1 weeks (80% CI, 11.9 to 22.6) with placebo (hazard ratio, 0.53; 80% CI, 0.30 to 0.92; one-sided P = .07). In the safety population (n = 39) treatment-related adverse events were mostly low grade. Patients received a median duration of 10 rucaparib or six placebo cycles on treatment. Treatment-related adverse events (all grades) of fatigue (63.2% v 30.0%), nausea (36.8% v 5.0%), rash (21.1% v 0%), and raised alanine aminotransferase (57.9% v 10%) were more common with rucaparib. CONCLUSION Maintenance rucaparib, following platinum-based chemotherapy, extended PFS in DRD biomarker-selected patients with mUC and was tolerable. Further investigation of poly ADP-ribose polymerase inhibition in selected patients with mUC is warranted.

4553 Background: The oral HIF-2α inhibitor belzutifan demonstrated antitumor activity with manageable safety as monotherapy in pts with heavily pretreated ccRCC and in combination with a VEGF-TKI in pts who previously received a PD-1/L1 inhibitor. KEYMAKER-U03B (NCT04626518) is phase 1/2, multicenter, multi-arm, open-label, adaptive umbrella study. We present preliminary results from arm B5 for belzutifan + lenvatinib. Methods: In all arms, adults with histologically confirmed ccRCC, KPS ≥70%, and disease progression on or after PD-1/L1 inhibitor and VEGF-TKI treatment (in sequence or in combination) were enrolled. In arm B5, pts received belzutifan 120 mg PO QD + lenvatinib 20 mg PO QD. The study comprised a safety lead-in phase to establish the recommended phase 2 dose (RP2D), followed by an efficacy phase. Primary end point for the safety lead-in phase was safety and tolerability to establish RP2D; co-primary end points of the efficacy phase were safety and ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include clinical benefit rate (CBR; CR + PR + SD ≥6 mo), DOR and PFS per RECIST v1.1 by BICR. Response will be presented in pts who had an opportunity to receive ≥2 postbaseline scans due to ongoing enrollment. PFS was evaluated in all enrolled pts and safety in all treated pts. End points will be evaluated in each arm separately; no comparisons will be made across arms. Results: As of September 29, 2022, 32 pts were enrolled and 30 received treatment. Median age was 60.5 y, 78% were male and 78% had intermediate/poor IMDC risk. 23 pts were on treatment at data cutoff date. Median follow up was 6.9 mo (range: 0.1-18.2). Safety of belzutifan 120 mg + lenvatinib 20 mg was manageable. Of 10 evaluable pts in the safety lead-in phase, only 1 experienced a dose-limiting toxicity (grade 1 dyspnea). Among pts who had opportunity for ≥2 postbaseline scans (n = 24), ORR was 50% (95% CI, 29-71; all PRs); CBR was 54% (95% CI, 33-74). Median DOR was not reached (NR; range: 1.4+ to 14.0+ mo); 74% of responders remained in response for ≥12 mo by KM estimation. For all enrolled pts, median PFS was 11.2 mo (95% CI, 4-NR); 6-mo rate was 55%. In the safety analysis, 28 pts (93%) experienced a treatment-related AE (TRAE), most commonly (≥40%) anemia (43%), fatigue (43%), and hypertension (43%). Grade 3-4 TRAEs occurred in 15 pts (50%); most commonly hypertension (27%) and anemia (17%). 1 pt experienced grade 2 hypoxia. No pt died due to a TRAE. Conclusions: Preliminary data from the belzutifan + lenvatinib combination exhibited promising antitumor activity in pts with ccRCC that progressed on PD-1/L1 inhibitors and VEGF-TKIs. Safety findings were consistent with individual profiles of each agent. The combination is being further evaluated in the phase 3 LITESPARK-011 study. Clinical trial information: NCT04626518 .

Background Temporary drug treatment cessation might alleviate toxicity without substantially compromising efficacy in patients with cancer. We aimed to determine if a tyrosine kinase inhibitor drug-free interval strategy was non-inferior to a conventional continuation strategy for first-line treatment of advanced clear cell renal cell carcinoma.Methods This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done at 60 hospital sites in the UK. Eligible patients (aged >= 18 years) had histologically confirmed clear cell renal cell carcinoma, inoperable loco -regional or metastatic disease, no previous systemic therapy for advanced disease, uni-dimensionally assessed Response Evaluation Criteria in Solid Tumours-defined measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) at baseline to a conventional continuation strategy or drug-free interval strategy using a central computer-generated minimisation programme incorporating a random element. Stratification factors were Memorial Sloan Kettering Cancer Center prognostic group risk factor, sex, trial site, age, disease status, tyrosine kinase inhibitor, and previous nephrectomy. All patients received standard dosing schedules of oral sunitinib (50 mg per day) or oral pazopanib (800 mg per day) for 24 weeks before moving into their randomly allocated group. Patients allocated to the drug-free interval strategy group then had a treatment break until disease progression, when treatment was re-instated. Patients in the conventional continuation strategy group continued treatment. Patients, treating clinicians, and the study team were aware of treatment allocation. The co -primary endpoints were overall survival and quality-adjusted life-years (QALYs); non-inferiority was shown if the lower limit of the two-sided 95% CI for the overall survival hazard ratio (HR) was 0middot812 or higher and if the lower limit of the two-sided 95% CI of the marginal difference in mean QALYs was -0middot156 or higher. The co-primary endpoints were assessed in the intention-to-treat (ITT) population, which included all randomly assigned patients, and the per-protocol population, which excluded patients in the ITT population with major protocol violations and who did not begin their randomisation allocation as per the protocol. Non-inferiority was to be concluded if it was met for both endpoints in both analysis populations. Safety was assessed in all participants who received a tyrosine kinase inhibitor. The trial was registered with ISRCTN, 06473203, and EudraCT, 2011-001098-16.Findings Between Jan 13, 2012, and Sept 12, 2017, 2197 patients were screened for eligibility, of whom 920 were randomly assigned to the conventional continuation strategy (n=461) or the drug-free interval strategy (n=459; 668 [73%] male and 251 [27%] female; 885 [96%] White and 23 [3%] non-White). The median follow-up time was 58 months (IQR 46-73 months) in the ITT population and 58 months (46-72) in the per-protocol population. 488 patients continued on the trial after week 24. For overall survival, non-inferiority was demonstrated in the ITT population only (adjusted HR 0middot97 [95% CI 0middot83 to 1middot12] in the ITT population; 0middot94 [0middot80 to 1middot09] in the per-protocol population). Non-inferiority was demonstrated for QALYs in the ITT population (n=919) and per-protocol (n=871) population (marginal effect difference 0middot06 [95% CI -0middot11 to 0middot23] for the ITT population; 0middot04 [-0middot14 to 0middot21] for the per-protocol population). The most common grade 3 or worse adverse events were hypertension (124 [26%] of 485 patients in the conventional continuation strategy group vs 127 [29%] of 431 patients in the drug-free interval strategy group); hepatotoxicity (55 [11%] vs 48 [11%]); and fatigue (39 [8%] vs 63 [15%]). 192 (21%) of 920 participants had a serious adverse reaction. 12 treatment -related deaths were reported (three patients in the conventional continuation strategy group; nine patients in the drug -free interval strategy group) due to vascular (n=3), cardiac (n=3), hepatobiliary (n=3), gastrointestinal (n=1), or nervous system (n=1) disorders, and from infections and infestations (n=1). Interpretation Overall, non-inferiority between groups could not be concluded. However, there seemed to be no clinically meaningful reduction in life expectancy between the drug-free interval strategy and conventional continuation strategy groups and treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.Funding UK National Institute for Health and Care Research. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

436 Background: A subset of mUC exhibits a DNA repair deficiency (DRD) phenotype predicting benefit from platinum based chemotherapy (PBC). We hypothesised that switch maintenance therapy with the PARP inhibitor rucaparib, in patients who have derived clinical benefit from PBC, would improve outcomes for patients with mUC harbouring a DRD biomarker. Methods: ATLANTIS is an adaptive, multi-comparison, phase II trial platform. It tests multiple biomarker selected maintenance therapies for mUC after 4 to 8 PBC cycles without disease progression. Biomarker allocation to the rucaparib comparison was based on ≥10% genomic loss of heterozygosity (%LOH) and/or somatic alteration in defined DRD associated genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD54L) and/or germline BRCA1 or BRCA2 alteration. Biomarker positive patients were randomised (1:1) to maintenance rucaparib 600 mg BID PO, or matched placebo, within 10 weeks of completing PBC, until disease progression. The primary endpoint was progression free survival (PFS). Statistical analysis (data cut 17/Nov/2021) was pre-planned to target a hazard ratio of 0.5. We selected a 20% 1-sided alpha for this signal seeking phase II trial with 85.4% power (requiring 30 PFS events in 40 patients). PFS (RECIST 1.1) was compared between trial arms, by intention to treat, within a Cox model incorporating baseline minimisation factors. Adverse events (AE) were assessed by CTCAE v4.03. Results: 74 of 279 (26.5%) screened patients were biomarker positive. 40 were randomised within the rucaparib comparison (Dec 2017-Dec 2020). Biomarker positive status was by high %LOH in 22 (55%), DRD gene alteration in 11 (27.5%) and both in 7 (17.5%). Patient characteristics (median age 70.5; 82.5% male; 87.5% bladder primary; 52.5% ECOG PS 0; 62.5% prior cisplatin; 45% visceral metastases) were balanced by treatment arm. 12 (60%) and 20 (100%) PFS events have occurred in the rucaparib and placebo arms respectively (median duration follow up 94.6 weeks in those still alive). Median PFS was 35.3 weeks (80% confidence interval (CI) 11.7-35.6) with rucaparib and 15.1 weeks (80% CI 11.9-22.6) with placebo (hazard ratio 0.53, 80% CI 0.30-0.92, 1 sided p = 0.07). In the safety population (n = 39) treatment related adverse events were mostly low grade. Rucaparib was tolerable with a median duration of 10 rucaparib or 6 placebo cycles on treatment. The most frequent treatment related AEs (all grades) of fatigue (63.2% vs 30.0%, p = 0.03), nausea (36.9% vs 5.0%, p = 0.03) and rash (21.1% vs 0%, p = 0.04) were more common with rucaparib respectively. Conclusions: Maintenance rucaparib, following PBC, extended PFS in DRD biomarker selected patients with mUC and is tolerable. Further investigation of PARP inhibition for mUC is warranted. Clinical trial information: 25859465.

Background: Cutaneous melanoma is an aggressive malignancy that is proposed to account for 90% of skin cancer-related mortality. Individuals with melanoma experience both physical and psychological impacts associated with their diagnosis and treatment. Health-related information is being increasingly accessed and shared by stakeholders on social media platforms. Objective: This study aimed to assess how individuals living with melanoma across 14 European countries use social media to discuss their needs and provide their perceptions of the disease. Methods: Social media sources including Twitter, forums, and blogs were searched using predefined search strings of keywords relating to melanoma. Manual and automated relevancy approaches filtered the extracted data for content that provided patient-centric insights. This contextualized data was then mined for insightful concepts around the symptoms, diagnosis, treatment, impacts, and lived experiences of melanoma. Results: A total of 182,400 posts related to melanoma were identified between November 2018 and November 2020. Following exclusion of irrelevant posts and using random sampling methodology, 864 posts were identified as relevant to the study objectives. Of the social media channels included, Twitter was the most commonly used, followed by forums and blogs. Most posts originated from the United Kingdom (n=328, 38%) and Spain (n=138, 16%). Of the relevant posts, 62% (n=536) were categorized as originating from individuals with melanoma. The most frequently discussed melanoma-related topics were treatment (436/792, 55%), diagnosis and tests (261/792, 33%), and remission (190/792, 24%). The majority of treatment discussions were about surgery (292/436, 67%), followed by immunotherapy (52/436, 12%). In total, 255 posts discussed the impacts of melanoma, which included emotional burden (n=179, 70%), physical impacts (n=61, 24%), effects on social life (n=43, 17%), and financial impacts (n=10, 4%). Conclusions: Findings from this study highlight how melanoma stakeholders discuss key concepts associated with the condition on social media, adding to the conceptual model of the patient journey. This social media listening approach is a powerful tool for exploring melanoma stakeholder perspectives, providing insights that can be used to corroborate existing data and inform future studies.

LBA4505 Background: Platinum-based chemotherapy (PBC) is an active first line therapy in mUC, but duration of response is usually short. We hypothesised that switch maintenance therapy with the tyrosine kinase inhibitor cabozantinib, in patients who have derived clinical benefit from PBC, would improve outcomes for mUC. Methods: ATLANTIS is an adaptive, multi-comparison, phase II trial platform. It tests multiple maintenance therapies for mUC patients who complete 4 to 8 cycles of PBC without disease progression. Whilst some patients were selected for randomisation into alternative comparisons in the platform based on putative predictive biomarkers, those who were not selected were randomised 1:1 to commence either cabozantinib 40mg once-daily or matching placebo within 10 weeks of completing PBC until progression. The primary endpoint was progression free survival (PFS) and 114 events in 140 patients (90% power, 20% 1-sided level alpha) were required to target a hazard ratio of 0.67. Due to a change in standard of care (maintenance avelumab), this was modified to 50 events in 57 patients (72.3% power, 20% 1-sided alpha) prior to the study closing early. PFS was compared between trial arms, by intention to treat, within a Cox model incorporating baseline minimisation factors. Secondary endpoints included overall survival (OS), response rate, maximum percentage decrease in measurable disease, safety and tolerability. Results: 30 patients were randomised to cabozantinib and 31 to placebo from 25 sites (Feb 2017-March 2021). Patient characteristics (median age 69.0 years; 75.4% male; 75.4% bladder primary; 67.2% ECOG PS 0; 70.5% prior cisplatin; 36.1% visceral metastases) were balanced by treatment arm. 25 (83.3%) and 26 (83.9%) PFS events had occurred in the cabozantinib and placebo arms. Median PFS was 13.7 weeks (80% confidence interval (CI) 12.1-23.3) with cabozantinib and 15.8 weeks (80% CI 11.3-23.6) with placebo (adjusted hazard ratio 0.89 favouring cabozantinib, 80% CI 0.61-1.3, 1-sided p = 0.35). There was no difference in overall survival (hazard ratio 0.80 (0.52-1.23) p=0.25). In the safety population (n = 61) treatment related adverse events were mostly low grade. The most frequent (all grades), fatigue (56.7% vs 32.2%, p = 0.02), hypertension (43.3% vs 12.9%, p = 0.01), nausea (30% vs 19.4%, p = 0.36) and diarrhea (40.0% vs 6.5%, p < 0.01), were more common with cabozantinib. Overall, cabozantinib was tolerable with median duration of treatment of 13 28-day cycles of cabozantinib or 10 of placebo. 13 (43.%) vs 3 (9.7%) patients required dose reduction in the cabozantinib and placebo arms respectively. Conclusions: Though tolerable, cabozantinib did not show a significant benefit compared to placebo when used in the switch maintenance setting following platinum based chemotherapy. Clinical trial information: ISRCTN25859465.

Background Immunotherapy and targeted therapy treatments are novel treatments available for patients with metastatic and adjuvant melanoma. As recently approved treatments, information surrounding the patients’ and caregivers’ experience with these therapies, perceptions of treatments, and the effect the treatments have on their day-to-day life are lacking. Such insights would be valuable for any future decision-making with regard to treatment options. Objective This study aims to use health-related social media data to understand the experience of patients with adjuvant and metastatic melanoma who are receiving either immunotherapy or targeted therapies. This study also included caregivers’ perspectives. Methods Publicly available social media forum posts by patients with self-reported adjuvant or metastatic melanoma (and their caregivers) between January 2014 to October 2019 were programmatically extracted, deidentified, cleaned, and analyzed using a combination of natural language processing and qualitative data analyses. This study identified spontaneously reported symptoms and their impacts, symptom duration, and the impact of treatment for both treatment groups. Results Overall, 1037 users (9023 posts) and 114 users (442 posts) were included in the metastatic group and adjuvant group, respectively. The most identified symptoms in both groups were fatigue, pain, or exanthema (identified in 5%-43% of patients dependent on the treatment group). Symptom impacts reported by both groups were physical impacts, impacts on family, and impacts on work. Positive treatment impacts were reported in both groups and covered the areas of work, social and family life, and general health and quality of life. Conclusions This study explored health-related social media to better understand the experience and perspectives of patients with melanoma receiving immunotherapy or targeted therapy treatments as well as the experience of their caregivers. This exploratory work uncovered the most discussed concerns among patients and caregivers on the forums including symptoms and their impacts, thus contributing to a deeper understanding of the patient/caregiver experience.

A 34-year-old man presented with an 8-day history of swelling and ptosis affecting the right upper eyelid. An MRI scan showed right superior rectus enlargement. Histology of an incisional biopsy of the muscle demonstrated metastatic choriocarcinoma to the orbit, positive for pan-cytokeratins, beta-HCG and GATA3. Possible primary sites included testis. An ultrasound of the testes identified bilateral testicular masses, highly suspicious for primary testicular malignancy. A CT scan of the chest, abdomen and pelvis identified disseminated metastatic disease conferring a poor prognostic germ cell tumour. The overall interpretation was of disseminated testicular choriocarcinoma and the patient is currently undergoing intensive chemotherapy.

TPS2665 Background: The gut microbiome is implicated as a biomarker of response to immune checkpoint inhibitors (ICIs), based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early reports suggest faecal microbial transfer may have therapeutic potential, converting ICI non-responders to responders. So far, identification of specific responsible bacterial taxa has been inconsistent between published studies, which limits future application. By culturing and metagenomic sequencing of stool sample bacteria, our group has identified a unique microbiome signature, which appears to be predictive of response to ICIs across all key published series as well as our own melanoma patient series (Robinson M et al, J Immunother Cancer 2020;8(suppl 3):A404). Because the patient numbers in all published series remain low, we are now further exploring and validating this microbiome signature in a larger scale study across several different cancer types. Methods: MITRE (Microbiome Immunotherapy Toxicity and Response Evaluation) is a UK NIHR portfolio multi-centre prospective study funded jointly by Cancer Research UK and Microbiotica (NCT04107168). Up to 1800 patients receiving ICIs will be recruited over a 5-year period. In the first stage, 300 patients with advanced melanoma (cohort 1: anti-PD1 monotherapy, cohort 2: anti-PD1+anti-CTLA-4 combination), renal cancer (cohort 3: anti-PD(L)1+kinase inhibitor, cohort 4: anti-PD1+anti-CTLA-4 combination) and non-small cell lung cancer (cohort 5: anti-PD(L)1 monotherapy, cohort 6: anti-PD(L)1+chemotherapy+anti-angiogenic) are being recruited, 50 patients to each cohort. A cohort-specific, simulation-based power calculation will then be performed, guiding subsequent recruitment. Stool and blood are collected prior to treatment, at 3, 6 and 12 months, or disease progression (whichever is sooner), as well as after any grade >3 immune-related adverse events. Patients collect and freeze their own stool samples which are cultured and subjected to shotgun metagenomic sequencing. Plasma, whole blood, buffy coat, RNA and PBMCs are being stored, for correlative studies. Any tumour, or organ biopsies, taken prior to and during treatment are also being collected. Clinical data collection includes treatment, disease response (using RECIST criteria) and toxicity. The primary outcome measure is 1 year progression-free survival. Patients are also asked to invite a household member to be part of the study control group. Recruitment started in July 2020. The Covid-19 pandemic hindered recruitment last year, but the protocol was amended to incorporate a Covid-19 substudy (to document testing, infection and vaccination) and adapt processes for remote trial delivery as much as possible. As of February 2021, 7 sites have opened, 17 patients and 5 household controls have been recruited. Clinical trial information: NCT04107168.

488 Background: UTUC is rarer than bladder UC and typically responds poorly to standard chemotherapy. Analysis of 220 biomarker-evaluable atezo-treated patients (pts) in phase II/III trials suggested worse outcomes in UT vs lower tract UC [Galsky, ESMO 2018]. We explored clinical outcomes in pts with UTUC (renal pelvis or ureter) treated with atezo in the SAUL study. Methods: The single-arm SAUL study (NCT02928406) [Sternberg, Eur Urol 2019] enrolled a broader pt population, including pts with poor clinical characteristics and/or immune-mediated conditions, more representative of real-world practice than typically enrolled in randomized phase III immunotherapy trials. Pts with urinary tract carcinoma received atezo 1200 mg q3w until disease progression/unacceptable toxicity. Baseline characteristics, safety and efficacy were analyzed in subgroups of pts with UTUC (subdivided into renal pelvis or ureter UC) vs bladder UC. Results: Baseline characteristics in the 4 subgroups were generally similar, except for a numerically lower proportion of pts with 0 prior lines of therapy for metastatic disease in the UTUC vs bladder UC subgroup (30% vs 41%). Treatment exposure, safety and efficacy are shown below. Conclusions: These exploratory analyses of SAUL showed very similar efficacy and safety in UT vs bladder UC. This provides reassurance that atezo is active and has an acceptable safety profile in pts with UTUC, who are generally expected to have worse outcomes than bladder UC pts. Clinical trial information: NCT02928406 . [Table: see text]

Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (<65 years, 65–74 years and ≥75 years) using univariable and multivariable analyzes. Eligible patients (n=448) were divided into age cohorts: <65 years (n=185), 65–74 years (n=154) and ≥75 years (n=109). Fewer patients in the oldest cohort (7.3%) received an anti-CTLA4 antibody containing regimen compared with the younger cohorts (21.1% and 17.5%). There was no significant difference overall in all grade or ≥G3 toxicities between age cohorts. Significantly fewer patients in the older (65–74 years and ≥75 years) age cohorts discontinued treatment because of toxicity (10.1% and 7.4%) compared with in the <65 years cohort (20.5%; p=0.006). Using logistic regression, only treatment type (ipilimumab containing) was significantly associated with all grade toxicity. However, there was a significantly lower incidence of all-grade endocrine toxicity in the oldest cohort (11.0%) compared with the youngest cohort (22.7%, p=0.02; OR 0.43, 95% CI 0.21 to 0.87), while all-grade dermatological toxicity showed the reverse trend (28.4% vs 18.9%; OR 1.85, 95% CI 1.04 to 3.30). Results were corroborated in the sensitivity analysis using only data from patients who received PD-1 inhibitor monotherapy. This multicenter, real-world cohort demonstrates that immune checkpoint inhibitor therapy is safe and well tolerated regardless of age, with no appreciable increase in adverse events in older adult patients.

Evidence on treatment outcomes and prognostic factors in elderly patients who undergo first-line treatment for metastatic renal cell carcinoma (mRCC) is mainly derived from subgroup analysis of randomized trials that enrolled fit elderly patients. Herein, we assessed safety, efficacy, and prognostic factors in our elderly mRCC patients who underwent first-line treatment with either pazopanib or sunitinib. Background: Elderly metastatic renal cell carcinoma (mRCC) patients are under-represented in clinical trials, whose results are therefore difficult to translate into routine management of older patients. We aimed at exploring treatment outcomes and prognostic factors in our real-life elderly mRCC cohort receiving first-line tyrosine kinase inhibitor (TKI) monotherapy. Patients and Methods: We retrospectively analyzed demographic and clinicopathological characteristics, and treatment data of elderly (>= 70 years old at first-line start) mRCC patients starting either pazopanib or sunitinib as first-line treatment in our institution between March 2012 and April 2018. Baseline characteristics included age-adjusted Charlson comorbidity index (CCI). Results: In total, the records of 35 elderly mRCC patients were identified and retrospectively analyzed. Overall response rate, median progression-free survival, and median overall survival were 20%, 9.7 months, and 21.6 months, respectively. Karnofsky performance status <= 70%, sarcomatoid features, absolute neutrophil count greater than upper limit of normal, and treatment-related Grade 3 arterial hypertension were independently associated with survival after multivariate analysis. Age-adjusted CCI was significantly associated with survival in univariate analysis only. The overall incidence of Grade 3 to 5 toxicities was 74%. Seven patients (20%) received early crossover to either sunitinib or pazopanib because of toxicity. Dose reduction was applied in 24 (73%) of the 33 patients who completed at least 1 cycle. Conclusion: First-line TKI monotherapy provided clinical benefit in our elderly mRCC cohort. Relatively frequent dose reductions helped to maintain an acceptable tolerability profile. Further research is warranted to explore the significance of prognostic factors in elderly mRCC patients. (C) 2019 Elsevier Inc. All rights reserved.

Metastatic brain tumors represent a significant proportion of tumors identified intraoperatively. A rapid diagnostic method, circumventing the need for histopathology studies, could prove clinically useful. As many spectroscopic studies have shown ability to differentitate between different tumor types, this technique was evaluated for use within metastatic brain tumors. Spectrochemical approaches [Raman and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) spectroscopy] were applied to determine how readily they may identify the primary site for the metastatic tumor. Metastases were from primary adenocarcinomas of lung (n = 7) and colorectum (n = 7), and for comparison, metastatic melanoma (n = 7). The objective was to determine if Raman or ATR-FTIR spectroscopy could delineate the origin of the primary tumor. The results demonstrate that there are marked similarities between the two adenocarcinoma groups and whilst Raman and ATR-FTIR can distinguish the three groups with limited success, classification accuracy is greatly improved when combining the adenocarcinoma groups. The use of such techniques in the clinical setting is more likely to be found intraoperatively, determining the presence of a tumor and suggesting the tumor class; however, traditional histopathology would still be needed to identify the primary origin of the tumor.

Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers.Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21).Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab.ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Immune checkpoint inhibitors have become standard of care in metastatic malignant melanoma management. Despite superior effectiveness to chemotherapy, significant immune-related adverse events (irAE) may occur, particularly if used in combination. Gastrointestinal irAEs were reported with different patterns of involvement. Here, we report the case of a patient who had ileal perforation as a complication of terminal ileitis, without colitis, induced by combination immune checkpoint blockade.

e15116 Background: Little data exists for the use of immune checkpoint inhibitors (ICI) in patients ≥80y old. Ageing is associated with immunosenescence, which may impact the efficacy and toxicity of immune-based therapies. Here we provide efficacy and immune related adverse event (irAE) data for patients ≥80y old and younger patient cohorts treated in routine clinical practice at 3 UK Cancer Centres: Guy’s and St Thomas’ NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust and University Hospitals of Leicester NHS Trust. Methods: Melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC) patients treated with ICIs between March 2016 – August 2018 were identified, and divided into five age-defined cohorts: < 50y, 50-59y, 60-69y, 70-79y, ≥80y. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with data censored on 5th February 2018. Frequency and severity of five common irAEs were determined: hepatitis, endocrinopathies, immune-related gastrointestinal, skin and rheumatological. Results: 386 patients aged 22 – 98y (median 67y) received single-agent nivolumab (21%), pembrolizumab (62%), ipilimumab (10%) or combination ipilimumab and nivolumab (7%). 12% of patients were aged < 50y, 18% were 50-59y, 29% were 60-69y, 28% were 70-79y and 13% were ≥80y. Response rates (partial + complete response) were similar across all age groups (53% < 50y, 29% 50-59y, 48% 60-69y, 43% 70-79y and 47% ≥80y). Median PFS was 10.6, 10.3, 10.0, 5.8 and 19.7 months and OS was not reached, not reached, 29.0, 18.3, and 20.9 months for patients < 50y, 50-59y, 60-69y, 70-79y and ≥80y, respectively. The rate of any grade irAEs was lowest in patients ≥80y (59%), and highest in patients < 50y (92%). Grade 3-5 irAEs were also less frequent in patients ≥80y (10%) than those < 50y and 60-69y (both 18%). Conclusions: Of 386 patients 13% were ≥80y with response rates comparable to younger patient cohorts and rates of irAEs lower than younger patient cohorts in this retrospective analysis of a heterogenous patient population. Our data suggests that ICIs are well-tolerated and efficacious in elderly patients and that age alone should not preclude ICI use.

e13551 Background: Identification of primary tissue origin of brain metastases can be histopathologically challenging. Initial diagnosis of malignancy can be provided on intraoperative tissue smears; however, it requires formal histopathological examination along with immunohistochemistry to reach a final diagnosis. On occasion this will still fail to determine primary origin. This study aims to demonstrate if Raman spectroscopy is able to determine primary tissue origin of brain metastasis of three common primary tumours. Methods: Formalin fixed paraffin embedded tissue from twenty brain metastasis comprising colorectal adenocarcinomas ( n= 7), lung adenocarcinomas ( n= 7) and melanomas ( n= 6) were obtained from the Brain Tumour NorthWest tissue bank. Sections (10-μm thick) were placed onto glass slides covered in aluminium foil and de-waxed prior to spectral acquisition. 25 spectra per section were collected at random, using a 785 nm laser at 1200 g mm-1grating with an acquisition time of 30 sec. Computational analysis within a MatLab environment was then conducted. Results: Following PCA-LDC analysis, classification accuracy of the three groups was; colorectal adenocarcinoma 71.3%, lung adenocarcinoma 71% and melanoma 70%. A one-way ANOVA showed statistically significant differences between the three groups, p = 0.0014. On combining adenocarcinoma groups accuracy increased to 87.8%, whilst melanoma fell to 68.9%. A student’s t-test confirmed statistical significance between the two groups, p < 0.0001. Conclusions: Raman spectroscopy can classify different tumours by type, though sensitivity and specificity is diminished if used to classify primary tissue origin of adenocarcinomas. Therefore for clinical use, such new tools may aid the clinician to determine tumour type intra-operatively but classic histopathology is still required for tissue origin confirmation. Such technologies may provide a useful adjunct to more conventional approaches; for instance, decreasing the number of immunohistochemical stains required to determine tissue origin. These results also suggest strong similarities between adenocarcinomas of different primary origins.