11026
Background: The pandemic in 2020 made us used to virtual learning, but as we recover from the pandemic, we are forced to rethink how we deliver education to trainees in medicine. The pandemic ...has led to a significantly decreased attention span and face to face interactions, in addition to an increased screen time. In our program, this led to us noting a lower engagement in the fellowship didactics as we recovered from the pandemic. This forced us to rethink how the Oregon Health & Science University (OHSU) hematology and oncology fellowship delivers educational content. After interviewing all stakeholders, we moved to an in-person fellow led didactic approach, under the mentorship of a faculty expert who helps trainees design content and is present for discussion. The rationale behind this approach was to boost peer-to-peer learning, supply relevant content and increase engagement. The fellows and faculty were provided guidelines about length of talk, presentation of data and use of interactive tools. Methods: After 6 months of introducing fellow led didactics, we surveyed all fellows and select faculty who were mentors on more than one occasion about their opinion. A survey link was sent to all 12 fellows and 18 faculty members who regularly took part in fellowship didactics. Results: All 12 fellows responded to the survey. On a Likert scale of 1-5, they scored improvement in knowledge at 4.58 (0.64) and rated both the content and presenter at 4.25 (0.43). A third felt that this way of delivering didactics was a lot better and the rest felt it was a little better. On the negative side, they felt that they were spending more time preparing content (40% spent 7-9 hours a month) but were optimistic about lesser commitment next year as we bank the PowerPoint presentations. Nine of the 18 (50%) invited faculty responded to the survey, and on a scale of 1-5, they rated their improvement of knowledge as 4.44 (0.68). They scored the content and presenter at 4.44 (0.5) and 4.56 (0.68) respectively. 88.9% felt that the didactics were either a little or a lot better, and 11.1% felt them to be the same. On average, they spent less time on the content than they did if they were presenting. Conclusions: Overall, both faculty and fellows felt that this method of delivering didactics in a hematology oncology fellowship program was more effective. The fellows felt that they needed to put in extra hours for preparation, but this will probably go down as they build on earlier presentations.
e20572 Background: Dermatologic adverse events (DAEs) affect a significant number of patients with non-small cell lung cancer (NSCLC) who are treated with epidermal growth factor receptor tyrosine ...kinase inhibitors (EGFR-TKIs). While many DAEs have been identified during clinical trials and included in FDA drug labels, patients have raised concerns about experiencing unexpected DAEs. This study reviews the FDA Adverse Events Reporting System (FAERS) to identify DAEs in EGFR TKIs approved in NSCLC that are not included in drug labels. Methods: FAERS was queried for DAEs between 2003 – 2023 for osimertinib, afatinib, ertlotinib, gefitinib and mobocertinib. The reporting odds ratio (ROR) was calculated to compare DAEs between these EGFR-TKIs and all other drugs in the database. DAEs were considered statistically significant if the lower limit of the ROR 95% confidence interval (CI) was > 1 and if there were ≥ 3 reported adverse reactions. Results: 67,480 adverse events were reported for the 5 EGFR-TKIs studied. DAEs constituted 30.3% (20,426) of all adverse event reports. We identified skin (skin fissures, eczema, lip swelling, and skin infection), nail (onychalgia and onychomadesis), and hair (abnormal hair growth and hair disorder) DAEs not previously included in EGFR-TKI drug labels. RORs with 95% CIs are summarized in the table. Conclusions: Real-world FAERS data complements clinical trial data in identifying specific DAEs affecting NSCLC patients treated with EGFR TKIs. Our findings highlight DAEs that were previously not described, aiding clinicians in educating patients about side effects and giving patients a more nuanced understanding of what to expect before undergoing treatment. Table: see text
e17018
Background: Advanced prostate cancer disproportionally affects older men (age ≥ 75 years). Despite representing only 26% of diagnoses, older men represent half of those diagnosed with ...metastatic disease and half of all prostate cancer deaths. Treatment options for CRPC include enzalutamide (enza), a competitive inhibitor of the androgen receptor, which shows improved overall survival and other cancer-specific responses in older men. However, enza is also reportedly associated with increased fall frequency of unclear pathophysiology. This pilot study examines strength, balance, and cognition in men before and 12 weeks after starting enza therapy for CRPC. Methods: This prospective single-arm study included men about to begin enza for CRPC, ≥ 65 years, able to ambulate independently. The following tests were administered at baseline and 12 weeks after initiation of enza: Sit-to-stand test (STS), Timed-Up-and-Go test, proprioception assessment, computerized dynamic posturography including sensory organization test (SOT), motor control test (MCT), and limits of stability; Functional Assessment of Cancer Therapy-Prostate, BPI-SF, Activities-specific Balance Confidence (ABC), Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire (IPAQ), and the Godin leisure-time exercise questionnaire (GLTEQ). Falls were assessed with self-report fall diaries and calls from study team to participants over the course of 12 months. Results: Twenty-five participants enrolled. Median age was 75 years. There were 23 (92%) with both baseline and 12-week assessments, and 21 (84%) participants had complete falls data. From baseline to the 12-week follow up, ABC scale scores decreased (median 90.4 to 85.2), GLTEQ scale scores decreased (median 31.4 to 28.0), and time sitting per day from IPAQ increased (4 hours to 5 hours). Of those evaluable for falls, 15 (71%) did not fall during the 12 months and 6 (29%) fell at least once. The fallers and non-fallers did not differ with respect to age or MoCA scores at baseline and on re-assessment. Those who fell performed more poorly on the STS test, the ABC and the dynamic posturography evaluations. Those who fell also had a higher level of activity by GLTEQ. Conclusions: This pilot study does not clearly elucidate the pathophysiology of falls in older men with CRPC taking enza but does provide useful and important guidance for the design of future studies in this area. Baseline and 12-week testing should be repeated at the 24-week time-point to allow for sufficient exposure to enza. To avoid confounding by practice effects, physical tests, particularly dynamic posturography, should be performed at least once prior to baseline assessment. Further research is needed to understand the mechanisms underlying the increased risk of falls previously observed in older men with CPRC taking enza.
447
Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but ...efforts to advance this paradigm have been complicated by a lack of (a) prospective studies, (b) rigorous approaches to assess and define clinical complete response (cCR), and (c) integration of novel therapies. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance. Patients not achieving cCR were recommended to undergo cystectomy. Coprimary endpoints included (1) cCR rate and (2) association between cCR and 2-year outcomes. The key secondary endpoint was the impact of pre-specified baseline genomic alterations on outcomes. Additional biomarkers to refine patient selection were also explored. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%). Median follow-up is 27 months. 72/76 patients underwent clinical restaging and a cCR was achieved in 33/76 (43%; 95% CI: 32%, 55%). One cCR patient opted for immediate cystectomy (ypTaN0M0). Outcomes are summarized in the Table. Baseline ERCC2, ATM, FANCC, or RB1 alterations were not, but tumor mutational burden ≥ 10 mutations/mb was, significantly associated with the composite endpoint of ypT0 (immediate cystectomy) or 2-year bladder-intact metastasis-free survival (BIMFS). On landmark analysis, VI-RADS (Vesical Imaging–Reporting and Data System) score (3-5 versus 1-2) on restaging MRI (central blinded review) was associated with inferior BIMFS (HR 4.5; p = <0.01) and MFS (HR 19.3; p <0.01). Circulating tumor DNA data will be presented at the meeting. Conclusions: TURBT followed by gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a substantial subset of patients with MIBC. ≥2-year bladder-intact survival is achieved in the majority of patients with a cCR. Clinical trial information: NCT03558087 . Table: see text
Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, ...cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes (ATM, RB1, FANCC and ERCC2) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. ClinicalTrials.gov identifier: NCT03451331 .
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4503
Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients ...with MIBC but efforts to advance this paradigm have been complicated by (a) lack of prospective studies exclusively testing cisplatin-based neoadjuvant chemotherapy, (b) lack of rigorous methods to define clinical complete response (cCR) and its association with long term outcomes and (c) limited understanding of the role of “salvage” cystectomy. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder/prostatic urethral biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance; otherwise, patients underwent cystectomy. Coprimary endpoints included (1) cCR rate and (2) ability of cCR to predict 2-year metastasis-free survival (MFS). The key secondary endpoint was the impact of genomic alterations in baseline TURBT (TMB, ERCC2, FANCC, RB1, ATM) on performance of cCR for predicting MFS. The cCR rate coprimary endpoint, and interim analysis of 1-year outcomes, are reported. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%) and 64 (84%) have completed post-cycle 4 restaging; 31/64 achieved a cCR (48%; 95% CI 36%, 61%). The median follow-up of cCR patients is 13.7 months (range, 2.5-24 months). One cCR patient opted for immediate cystectomy (pTaN0M0). Outcomes for the entire cohort are summarized in the table below. Local recurrence has occurred in 8/31 cCR patients and 6 underwent cystectomy (pT0N0 = 1, pTaN0 = 1, pTisN0 =1, pT2N0 = 2, pT4N1 = 1). TMB ≥ 10 mut/Mb (p=0.02) or mutant ERCC2 (p=0.02) were associated with cCR or pT0. Conclusions: TURBT + gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a large subset of patients with MIBC. 1-year bladder intact survival is possible though the durability of responses, and role of genomic biomarkers in management algorithms, requires longer follow-up. Clinical trial information: NCT03558087. Table: see text
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4518
Background: Neoadjuvant cisplatin-based chemotherapy (CT) prior to radical cystectomy (RC) improves overall survival (OS) in MIBC, but about half of pts are cisplatin-unfit or ...refuse it. Neoadjuvant immune checkpoint inhibitors can induce high pathologic complete response rate (ypT0N0). The combination of anti-PD-1 (N) and anti-KIR (L) is hypothesized to be safe and have significant activity based on the complementary and possibly synergistic roles in regulating adaptive and innate immune response in MIBC. Methods: This is a phase Ib multi-institutional trial in pts with localized MIBC treated with 2 neoadjuvant doses (4 weeks apart) of N alone (480 mg) in cohort 1 or N (480 mg) + L (240 mg) in cohort 2 prior to RC without adjuvant therapy (NCT03532451). Cohorts were enrolled sequentially and were not randomized. Key eligibility criteria included stage cT2-4aN0-1M0, ≥20% tumor content at TURBT and cisplatin-ineligibility (Galsky criteria) or refusal. Primary endpoint was safety manifested as rate of ≥G3 treatment related adverse events (TRAE) assessed in each cohort with CTCAE v5.0. Key secondary endpoints included the % of pts who had RC > 6 weeks after last neoadjuvant dose due to TRAE, CD8+ T cell density at RC, ypT0N0 and < ypT2N0 rates, CD8+ T cell density change between TURBT and RC, recurrence-free survival (RFS) and biomarkers in tumor tissue, blood and urine. Results: Among 43 pts enrolled (13 cohort 1, 30 cohort 2), median age was 75 (51-89), 67% were men, all had PS ECOG 0-1. Pts were cisplatin-ineligible due to impaired renal function (47%) and hearing loss (37%), while 14 % refused cisplatin. At baseline, 37 pts had cT2 stage, 2 had cN1 and 3 cNx. In cohort 1 and 2, 13 and 29 pts, respectively, completed intended neoadjuvant treatment, and 41/43 underwent RC (12/13 cohort 1, 29/30 cohort 2). One pt progressed to metastatic disease prior to RC (cohort 1) and 1 withdrew consent prior to being treated (cohort 2). Additionally, 1 patient was found to have cervical cancer at RC. Median time from last neoadjuvant dose to RC was 27 (95%CI: 24-29) days. There was no RC delayed > 6 weeks from treatment completion due to TRAE. G3 TRAEs occurred in 0% with N and 6.7% (90%CI 1.2-19.5%) in N+L (1: arthralgia, 1: gout, 2: hip pain) that all resolved. No G4/5 TRAEs occurred. Of 40 pts with MIBC and RC, ypT0N0 rates for N and N+L were 8% and 18%, while < ypT2N0 rates were 17% and 29%, respectively. Data on RFS and OS, and biomarker data were not yet mature. Conclusions: Neoadjuvant N alone and N+L combination prior to RC were safe, feasible and well tolerated in cisplatin-ineligible pts with MIBC, but ypT0N0 rates were unexpectedly low, especially with N alone. Two phase 3 trials (NCT03661320; NCT04209114) are evaluating the peri-operative role of N + chemotherapy +/- Linrodostat in cisplatin-fit and N +/- Bempeg in cisplatin unfit patients and are also assessing biomarkers. Clinical trial information: NCT03532451.
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6512
Background: A trend in cancer treatment is the growing number of high-priced therapies which offer marginal clinical benefits. This has led ASCO to issue guidelines stressing the ...importance of discussing treatment costs with patients. There are many identified barriers which limit communication of cost including oncologists’ fears that patients may view this discussion as inappropriate. We attempted to assess cancer patients’ views on discussion of treatment costs with their oncologists, as well as, their views on high-cost drugs (HCDs), including the belief that there is a cohort of patients who would forgo high-priced treatment even if there was no out-of-pocket expense. Methods: We surveyed patients with advanced prostate cancer. The survey consisted of demographic information and an 11-item questionnaire. We also gave them a hypothetical scenario in which they were asked how much they would be willing-to-pay (WTP) for a $100K drug that would improve survival on average by four months with minimal side-effects (modeled after Provenge). The survey was administered to patients in clinic prior to their visit. Results: Of the patients approached, 169 responded (88% response rate). Seventeen percent stated they would not want treatment with HCDs even if they had no out-of-pocket expenses (more likely to be older (>70) and have an annual household income of >$60K). Another 21% stated they would accept treatment only if they had no out-of-pocket expenses. The median WTP for the hypothetical drug was $20K. Most patients (79%) agree that a discussion of costs with their physician is appropriate and 69% would want to have this discussion. Most patients (82%) agree that prognosis is important when making treatment decisions however 66% of patients did not know their cancer stage. Only 37% agree that the oncologist or the patient should consider the country’s healthcare costs when making treatment decisions. Conclusions: Prostate cancer patients clearly want to have discussions regarding costs-of-care with their oncologists. There is a group who would forgo treatment with high-cost drugs that yield only modest survival benefits. Their motivation is unknown, but is hypothesized to reflect a value-based judgment.
