Ineligible Cohort Research Articles

EPS6.05 Clinical outcomes in concurrent elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treated vs. ineligible cohorts in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) during COVID-19

EPS6.05 Clinical outcomes in concurrent elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treated vs. ineligible cohorts in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) during COVID-19

Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004.

4516 Background: Immunotherapy in the perioperative setting of MIUC appears promising. The AURA trial (NCT03674424) investigated the addition of avelumab to neoadjuvant dose-dense MVAC (ddMVAC) or cisplatin-gemcitabine (CG) respectively, followed by surgery in the cisplatin-eligible cohort. The primary endpoint was previously reported with high pathological complete response (pCR) rates with each cisplatin-based regimen. In the cisplatin-ineligible cohort, pts were randomized to neoadjuvant A alone or in combination with paclitaxel-gemcitabine (PG) followed by surgery. Avelumab monotherapy showed encouraging pCR but the addition of PG did not provide any benefit. Here, we report the survival data from cisplatin-eligible and ineligible cohorts of the AURA trial. Methods: In the cisplatin-eligible cohort, 79 pts were randomly assigned to the ddMVAC-A (n=39) or CG-A (n=40) groups. In the cisplatin-ineligible cohort, 58 pts were randomly assigned to the PG-A (n=29) or A (n=29) groups. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method at 12 months and 36 months for the overall cohort and by subgroups. Results: Median follow-up was 33 months and 45 deaths were reported. In the cisplatin-eligible cohort, 12-month DFS was 92% (95% CI, 83-96%) and 36-month DFS was 72% (95% CI, 57-83%). For ddMVAC-A group: 97% and 77%, respectively. For CG-A group: 86% and 68%. Overall, 12-month OS was 89% (95% CI, 80-95%) and 36-month OS was 73% (95% CI, 61-83%). For ddMVAC-A: 95% and 87%. For CG-A: 84% and 61%. Among the ypT0N0 pts, no events were registered within 12 months of follow-up showing a DFS rate of 100% for both arms. At 36 months no events were reported for pts treated with ddMVAC-A and two for CG-A showing DFS rates of 100% and 78% respectively. In the cisplatin-ineligible cohort, 12-month DFS was 60% (95% CI, 46-72%) and 12-month OS was 71% (95% CI, 57-81%). For PG-A: 52% and 67%. For A: 68% and 75%. Among the ypT0N0 pts, no DFS events occurred within 12 months. Data for 36-month are not yet mature. Overall, the main cause of death was disease progression (73%). Conclusions: The addition of neoadjuvant avelumab to cisplatin-based chemotherapy results in a high DFS and OS at 12 and 36 months respectively, especially in pts with complete response to neoadjuvant treatment. Combination with ddMVAC regimen offers robust activity. Cisplatin-ineligible pts had lower survival outcomes with no benefit of PG addition. Clinical trial information: NCT03674424 . [Table: see text]

P025 The haves and the have nots: characterising the CFTR protein modulator ineligible cohort in a large paediatric cystic fibrosis (CF) centre

P025 The haves and the have nots: characterising the CFTR protein modulator ineligible cohort in a large paediatric cystic fibrosis (CF) centre

Racial Disparities in Endometrial Cancer Clinical Trial Representation: Exploring the Role of Eligibility Criteria.

This study aimed to determine whether Black patients with recurrent endometrial cancer were more likely than White patients to be ineligible for a recently published clinical trial due to specific eligibility criteria. Patients with recurrent or progressive endometrial cancer diagnosed from January 2010 to December 2021 who received care at a single institution were identified. Demographic and clinicopathologic information was abstracted and determination of clinical trial eligibility was made based on 14 criteria from the KEYNOTE-775 trial. Characteristics of the eligible and ineligible cohorts were compared, and each ineligibility criterion was evaluated by race. One hundred seventy-five patients were identified, 89 who would have met all inclusion and no exclusion criteria for KEYNOTE-775, and 86 who would have been ineligible by one or more exclusion criteria. Patients in the ineligible cohort were more likely to have lower BMI (median 26.5 vs. 29.2, P <0.001), but were otherwise similar with regard to insurance status, histology, and stage at diagnosis. Black patients had 33% lower odds of being eligible (95% CI: 0.33-1.34) and were more likely to meet the exclusion criterion of having a previous intestinal anastomosis, but the result was not statistically significant. If this criterion were removed, the racial distribution of those ineligible for the trial would be more similar (46.4% Black vs. 42.2% White). Clinical trial eligibility criteria may contribute to the underrepresentation of racial groups in clinical trials, but other factors should be explored. Studies to quantify and lessen the impact of implicit bias are also needed.

Identification of patients with metastatic urothelial cancer not able to receive maintenance avelumab.

702 Background: Maintenance avelumab following frontline platinum-based chemotherapy for metastatic urothelial cancer (mUC) is associated with survival benefit. Eligibility to receive avelumab maintenance requires receiving 4-6 cycles chemotherapy without disease progression. Not all patients complete 6 cycles of chemotherapy or meet eligibility to receive avelumab and these patients may need to have alternative therapies. Here we present real world data to assess whether baseline characteristics can be used to identify patients unable to complete 6 cycles of chemotherapy and whom may not be eligible for maintenance avelumab. Methods: This retrospective audit was performed at Barts Cancer Centre for consecutive patients from January 2010 until August 2023. Patients who received frontline gemcitabine and cisplatin/carboplatin chemotherapy for advanced mUC were included. Eligibility for avelumab is defined as completing 4-6 cycles of chemotherapy without disease progression (PD). Characteristics of patients completing 6 cycles of chemotherapy, versus those who do not were described. Chi-squared tests were conducted to compare characteristic between the two groups, using SPSS v28. Results: 265 patients receiving frontline systemic therapy were identified over a 13-year period. 242 (91%) received Gem/Cis or Gem/Carbo chemotherapy. 151 (63%) patients were eligible to receive maintenance avelumab. 91 (38%) patients were not eligible due to receiving less than 4 cycles chemotherapy (68%) or due to PD (75%), or both. 91 (38%) patients completed 6 cycles of chemotherapy. Having a low baseline Hb &lt;100g/dl was the only baseline characteristic associated with receiving less than 6 cycles chemotherapy (p=0.002). 33% of patients who completed less than 6 cycles chemotherapy had a Hb &lt;100g/dl, compared to 10% of the patients who completed chemotherapy (p=0.002). Any dose delays was associated with a lower likelihood of being eligible to receive avelumab (32% and 18% dose delays in avelumab eligible vs ineligible cohorts, respectively (p&lt;0.001). Patients with any dose delays had more frequently received carboplatin (65% vs 39%, p=0.012) and had visceral metastases including liver metastases (63% vs 39%, p=0.014), compared to those without dose delays. Conclusions: Specific baseline factors predispose to an inability to deliver 6 cycles of chemotherapy without complications or progression. These patients are less likely to receive maintenance avelumab. These data help the optimise number of cycles offered to patients in mUC.

Acute oncology care at home for post-chemotherapy monitoring in patients with multiple myeloma.

58 Background: Hospitalization at Home (HaH) has demonstrated clinical efficacy and improved patient experience in general medicine inpatients. Mount Sinai Health System (MSHS) HaH enrolls oncology patients with active disease admitted for acute general medical conditions and for active chemotherapy. We performed a case-control study of our institution’s experience with HaH in multiple myeloma (MM) patients admitted for elective chemotherapy. Methods: We conducted a retrospective chart review of MM patients who received inpatient chemotherapy with dexamethasone, cyclophosphamide, etoposide, and cisplatin with or without bortezomib ((V)-DCEP) and then enrolled in HaH from September 2020 to May 2023. HaH eligibility required meeting established institutional HaH admission criteria, including geographical limitations. The control group were randomly selected MM patients admitted for (V)-DCEP who lived in a zip-code excluded from HaH’s catchment zone. Demographics, social situation, indication for inpatient stay, and HaH admission were extracted from the electronic health record. Primary endpoint was 30-day readmission from final place of discharge. A key secondary endpoint was rate of successful HaH admission, defined as discharge from HaH for complete recovery from the acute condition. Results: Twenty-two patients with MM, with 24 episodes of care, enrolled on HaH for post-chemotherapy monitoring. Our control cohort had 32 patients with 32 episodes of care. In the HaH population, the median age was 57, 73% (n = 16) male, 23% (n = 5) White, 41% (n = 9) Black, 14% (n = 3) Asian, 18% (n = 4) Hispanic, and 55% (n = 12) had either Medicaid or were dual Medicare/Medicaid eligible. In the HaH ineligible group, the median age was 67.5, 63% (n = 20) male, 56% (n = 18) White, 13% (n = 4) Black, 6% (n = 2) Asian, 19% (n = 6) Hispanic, and 32% had either Medicaid or were dual Medicare/Medicaid eligible. In the HaH population, the median inpatient length of stay was 6.5 days compared to 17.5 days in the HaH ineligible cohort (p &lt; 0.001). Mean length of HaH stay was 8.83 days, which saved our health system 212 inpatient-bed days. In the HaH cohort, there were 33% (n= 8) 30-day readmissions, 38% (n = 3) of which were unplanned; similarly, in the HaH ineligible population, there were 38% (n = 12) 30-day readmissions, with 33% of these readmissions unplanned (p = 0.97). Successful HaH admissions occurred for 92% of care episodes. No significant adverse outcomes or issues related to the care delivery or social support. Conclusions: The MSHS HaH program demonstrated safety and feasibility in caring for oncology patients admitted for elective chemotherapy. Hospital readmission frequency was the same across both cohorts. We were able to successfully care for the majority of patients with MM and had significant inpatient bed day savings. HaH should be expanded to other groups of specialized patients, leveraging disease-specific clinical pathways.

Benchmarking maintenance therapy survival in first-line advanced urothelial carcinoma using disease modeling.

4575 Background: First-line (1L) maintenance avelumab (maintA) in patients with advanced urothelial carcinoma (aUC) prolonged overall survival (OS) in the JAVELIN Bladder 100 trial. JAVELIN measured OS from the initiation of maintA among a subgroup of the overall aUC 1L treated population, including only patients who did not progress with 1L platinum-based therapy (PBT) and remained progression free during a 4-10 week treatment-free interval following completion of 1L PBT. As such, patients who progressed on or immediately following PBT were not included in the trial. To address this, we used disease modeling to estimate maintA OS measured from initiation of 1L PBT to align maintA OS with the common initiation point to benchmark with other 1L clinical trials. Methods: We developed a simulated cohort to estimate OS from initiation of 1L PBT in all aUC patients including those who received maintA. Eligibility for maintA (PBT progressed vs not progressed) was assessed at 5.6 months post-initiation of 1L PBT, accounting for 6 PBT cycles and a nominal 6-week treatment-free interval. Median OS of 14.3 months from the 1L PBT arm of a recent 1L trial, KEYNOTE-361, was used to represent the OS of the simulated cohort of 1L aUC patients. The simulated cohort was stratified by eligibility for maintA. Among the 1L treated population, 57% were projected to be progression-free and eligible for maintA based on progression-free survival (PFS) from KEYNOTE-361. Among those eligible, 85% were assumed to receive maintA based on expert clinical input. OS of maintA eligible patients was 21.4 months from JAVELIN. Our disease model estimated OS among a maintA ineligible simulated cohort, which was combined with the maintA eligible cohort to yield an estimated OS in the overall aUC population measured from initiation of 1L PBT. Results: Approximately 50% of the 1L modeled population receive maintA (i.e., 57% eligible x 85% treated). Our approach estimated a median OS of 9.9 months for the maintA ineligible cohort and 27.0 months for the maintA eligible cohort. Combined, the estimated median OS with maintA, measured from initiation of 1L PBT, in all 1L-treated aUC patients was 15.8 months (vs 14.3 months with PBT only in 1L). Conclusions: MaintA improves OS for eligible patients, however our simulation model suggests a significant proportion of patients will not receive MaintA. The estimated OS of 15.8 months for the population-level impact of maintA, accounting for patients ineligible for 1L maintA, demonstrates remaining unmet need in the overall 1L aUC population.

Avelumab as the basis of neoadjuvant regimen in platinum-eligible and -ineligible patients with nonmetastatic muscle-invasive bladder cancer: AURA (Oncodistinct-004) trial.

4517 Background: Nearly half of the patients (pts) diagnosed with non-metastatic muscle invasive bladder cancer are unfit for cisplatin therapy and no alternative options of neoadjuvant treatment exist. Avelumab (A), a monoclonal antibody directed against PD-L1, showed efficacy in advanced urothelial cancer. We report preliminary data assessing preoperative avelumab associated with paclitaxel and gemcitabine or avelumab alone in the cisplatin ineligible cohort. The results of the cisplatin eligible cohort were reported at ESMO 2021. Methods: AURA is a prospective, multicenter, randomized, phase II trial for pts with cT2-4aN0-2M0 bladder carcinoma. Pts were enrolled in two separated cohorts based on eligibility for cisplatin chemotherapy. Cisplatin ineligible pts received 4 cycles of paclitaxel-gemcitabine (PG) plus A every 2 weeks or 4 cycles of A every 2 weeks (1:1). Primary endpoint was pCR rate (ypT0/isN0) with the objective, in each arm, to show pCR rate &gt; 5% (90% power reached in case of pCR rate &gt; 25%). Two-step design was used with planned interim analysis after 12 evaluable pts per arm. Secondary endpoints were pathologic downstaging rate ( &lt; ypT2N0) and safety. Results: A total of 56 cisplatin-ineligible pts were evaluable. For PG + A arm (n = 28): median age was 72 years (41-80), 93% male. For A alone arm (n = 28): median age was 75 years (49-89), 93% male. One patient did not undergo surgery due to progression in the A arm but was included in intention to treat analysis. Five pts did not receive the 4 cycles of treatment; reasons included toxicity (n = 3) for PG + A arm and patient/physician decision (n = 2) for A arm. pCR was achieved in 5 pts (18%; 95%CI 6%-37%) treated with PG + A and 10 pts (36%; 95%CI 19%-56%) treated with A. Downstaging to &lt; ypT2N0 was achieved in 6 pts (21%; 95%CI 8%-41%) and 11 pts (39%; 95%CI 22%-59%), respectively. Median time from treatment initiation to surgery was 82 days (55-144) for PG + A arm and 67 days (38-89) for A arm. Most common irAEs of any grade were asthenia (15%), skin toxicity and myalgia/arthralgia (each 5%). There were 2 pts in the PG + A arm with grade 3 irAEs (hepatitis and pneumonitis) that caused A discontinuation for 1 patient. No treatment-related deaths were reported. Conclusions: Neoadjuvant single agent avelumab resulted in high pCR and was safely administered without compromising surgical resection. Our results suggest that the addition of taxane-gemcitabine regimen to avelumab may reduce avelumab efficacy with low pCR rate. Survival analysis and correlative studies are underway. Clinical trial information: NCT03674424.

Representativeness of the GALACTIC-HF Clinical Trial in Patients Having Heart Failure With Reduced Ejection Fraction.

BackgroundRandomized clinical trials in populations with heart failure with reduced ejection fraction may not be reflective of the general population with heart failure with reduced ejection fraction. Our study assessed the representativeness of the GALACTIC‐HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patient population in Kaiser Permanente Southern California.Methods and ResultsWe identified 9770 patients with a diagnosis of heart failure with reduced ejection fraction from 2014 to 2018 using electronic health records. Four mutually exclusive cohorts were created, including GALACTIC‐HF–ineligible cohorts: (1) not taking guideline‐directed medical therapy (GDMT) and (2) taking GDMT; and GALACTIC‐HF–eligible cohorts with: (3) ejection fraction (EF) ≤28% and (4) EF 29% to 35%. Patients were followed for 30‐day and 1‐year mortality and 30‐day, 180‐day, and 1‐year hospitalization. Overall, 3626 (37.1%) met GALACTIC‐HF inclusion criteria with EF ≤35%, and 2367 (65.3%) of those individuals had EF ≤28%. The risk of 1‐year mortality was lower among all cohorts versus the GALACTIC‐HF–ineligible cohort not taking GDMT (hazard ratio, 0.80 [95% CI, 0.70–0.91], 0.84 [95% CI, 0.72–0.98], and 0.62 [95% CI, 0.51–0.75] for the GALACTIC‐HF–ineligible cohort taking GDMT and GALACTIC‐HF‐eligible cohorts with EF ≤28% and 29%–35%, respectively). Compared with the GALACTIC‐HF–ineligible cohort not taking GDMT, the short‐term hospitalization risk at 30 and 180 days were similar for both GALACTIC‐HF–eligible cohorts and the hospitalization risk at 1 year was similar for the GALACTIC‐HF–eligible cohort with EF ≤28%.ConclusionsA large portion of patients with heart failure with reduced ejection fraction with low EF met inclusion criteria for the GALACTIC‐HF trial and, despite being on GDMT, had hospitalization rates similar to those not taking GDMT, suggesting potential benefits from other innovative treatments.

Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial)

IntroductionCisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies.Methods and analysisOncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety.Ethics and disseminationThe study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov (NCT03674424).

The epidemiology of rubella, 2007–18: an ecological analysis of surveillance data

As of 2018, the rubella vaccine had been incorporated into the national immunisation schedule of 168 countries, representing 87% of the world's population. Countries have used different strategies to reduce the burden of congenital rubella syndrome (CRS), such as vaccinating only females. Given the different strategies, and that 26 countries still had not introduced the vaccine, we analysed global rubella surveillance data to understand rubella epidemiology and the effect of vaccination. In this ecological analysis, we evaluated surveillance data on rubella cases that had been reported to WHO from 2007 to 2018, by age, vaccination history, and onset year. Cases were classified as either being vaccine eligible or ineligible on the basis of the country's vaccination strategy and the birth year of the person. We required all cases be confirmed by laboratory testing or that they were epidemiologically linked, and we excluded cases defined only by clinical symptoms. Incidence per million people was calculated by use of World Population Prospects data. Between Jan 1, 2007, and Dec 31, 2018, from data reported to WHO as of Jan 3, 2020, there were 139 486 reported rubella cases, of which 15 613 (11%) were vaccine eligible. Annual incidence ranged from 13·9 cases per million in 2007 to 1·7 cases per million in 2018. In all years, absolute and proportional global incidence were higher among vaccine ineligible cohorts than eligible cohorts. In vaccine ineligible cohorts, 87 666 (74%) of 118 308 cases were in children younger than 15 years, compared with 8423 (54%) of 15 613 cases in vaccine eligible cohorts. Vaccine ineligible women of reproductive age (WRA) had a higher incidence than vaccine eligible WRA, except in 2011-12. Vaccination has been successful in decreasing the burden of rubella, regardless of the strategy used. WRA remain at risk, but the risk is higher in those countries that have yet to introduce the vaccine. These countries should introduce the rubella-containing vaccine as soon as possible, to eliminate rubella, and to prevent the morbidity and mortality associated with CRS. None.

Phase II neoadjuvant (N-) gemcitabine (G) and pembrolizumab (P) for locally advanced urothelial cancer (laUC): Interim results from the cisplatin (C)-ineligible cohort of GU14-188.

5019 Background: Patients (pts) with laUC who are C-ineligible have inferior survival compared to counterparts who receive C based N-therapy and have a pathologic response at radical cystectomy (RC). Cohort 2 (C2) of the GU14-188 trial is designed to assess the tolerability and efficacy of N- G and P in laUC pts who are C-ineligible. Methods: Eligible pts for C2 were surgical candidates and C-ineligible with cT2-4aN0M0 bladder UC or mixed histology. Enrollment followed a Simon 2-stage design for H0 of interval futility which was rejected at stage 1, and fully enrolled. Pts were treated with N- G (1000mg/m2) on days 1, 8, and 15 of a 28 day cycle (cy) for a total of 3 cy, and overlapped with P 200mg every 3wks starting on cy 1 day 8 x 5 doses. Minimum criteria for evaluation of safety: 1 dose of P, and for efficacy: 2 doses P and RC. The primary endpoint of pathologic muscle invasive response rate (PaIR, ≤pT1N0) was assessed at RC and designed for 86% power, 4% significance to detect PaIR difference from 18 to 40%. Molecular subtyping is planned. Results: 37 pts were enrolled to C2 with a median (mdn) age of 72, 70% male, 55% &gt; cT2. C-ineligibility was due to renal function (49%), hearing (30%), neuropathy (12%). Mdn per-pt doses given (intended) for P:5(5) and G:9(9). The PaIR was 51.6% (95%CI 0.35, 0.68), P0 (ypT0N0) rate of 45.2%, and neither correlated with baseline PD-L1 score. Downstage to PaIR occurred in 57% of pts with cT2, and 47% of &gt; cT2. Mdn time to RC from last dose was 5.6wks. Six were not included in the primary analysis: 3 (8.1%) did not have RC due to progression (RFS censored), 2 did not receive required protocol therapy, and 1 withdrew consent. At mdn follow up of 10.8mo (4-24), the estimated 12mo RFS, OS, and DSS is 74.9%, 93.8%, and 100%, respectively. Treatment related AE included grade (gr) 3/4 neutropenia (24%), anemia (13%), and platelets (5%). There were no gr 4 non-heme AE, and of 14 (36%) pts with gr 3, 12 did not preclude RC. Of these, there were 4 gr 3 investigator assessed immune related adverse events (IAirAE) of pneumonitis (5%), colitis (3%), and AST elevation (3%). Though IAirAE improved, protocol therapy was discontinued in 3 pts: 2 did not have RC due to progression. Conclusion: N- G with P in C-ineligible pts with laUC is feasible with manageable toxicity, and has a pathologic downstage rate comparable to standard of care in the C-eligible population. G and P warrants further study with component contribution as a C- free N- option in laUC. Clinical trial information: NCT02365766 .

Evaluation of Maintenance Therapy in Myeloma in an Asian Population

Background: Maintenance therapy has garnered much interest in multiple myeloma (MM) owing to the incurable nature of the disease. Maintenance therapy has so far been shown to improve progression-free survival (PFS), but not always overall survival (OS). However, the benefit in the Asian population in the real world remains unknown. In real world practice, implementation of maintenance therapy is heterogeneous and often based on physician choice in Asia.Method: We included newly-diagnosed MM patients who were treated with novel agent-based induction therapy, with complete maintenance, transplantation and ISS data from year 2002 in our institution. We divided them into transplant eligible and ineligible cohorts. For each cohort, we evaluated the difference in OS, progression-free survival to first relapse (PFS1), and progression-free survival to second relapse (PFS2) between patients with and without maintenance therapy. We further evaluated if certain subgroup of patients would benefit more from maintenance therapy. Lastly, we evaluated if there was any difference in OS, PFS1, and PFS2 for patients according to the types of immunomodulatory drugs (IMiDs) used for maintenance therapy.Results: Among the 247 evaluable patients, 56 (22.6%) patients received maintenance therapy and 191 patients did not. The maintenance therapies received included thalidomide (n=31), lenalidomide (n=18), and bortezomib (n=7). We included patients from all ISS groups: ISS stage I (n=40), ISS stage II (n=98), and ISS stage III (n=109); and both transplant eligible (n=123) and ineligible (n=124) patients. All patients received novel agents for induction therapy, including proteasome inhibitor (n=72), immunomodulatory agent (n=92), and both proteasome inhibitor and immunomodulatory agent (n=83).For the transplant eligible patients, maintenance therapy was given for 33.3% of the ISS stage I patients, 34.0% of the ISS stage II patients, and 16.3% of the ISS stage III patients. On the other hand, for the transplant ineligible patients, maintenance therapy was given for 12.5% of the ISS stage I patients, 14.5% of the ISS stage II patients, and 23.3% of the ISS stage III patients.Our study showed that for the transplant eligible patients, maintenance therapy did not result in any significant difference in OS, PFS1, or PFS2 (P=0.069, 0.685, 0.350 respectively). However, for the transplant ineligible patients, there was a significant improvement in OS (median OS 119 mo vs 42 mo; P=0.024) and PFS1 (median PFS1 42 mo vs 19 mo; P=0.048), but not PFS2 (P=0.373), with maintenance therapy. Subgroup analysis showed that the OS benefit was mainly seen in the ISS stage III group (median OS 119 mo vs 38 mo; P=0.017) and there was a trend towards PFS1 benefit (median PFS1 41 mo vs 16 mo; P=0.060) with maintenance therapy. We combined the ISS stage I and II patients as the lower risk group for evaluation and our evaluation did not show any OS, PFS1 or PFS2 benefit of maintenance therapy in this cohort (P=0.373, 0.292, 0.251 respectively). We did not see any difference in OS, PFS1, and PFS2 (P=0.444, 0.170, and 0.512 respectively) whether patients had thalidomide, or lenalidomide, or no maintenance.Conclusion: Our study in this Asian population shows that maintenance therapy is not routinely given in clinical practice. For the transplant eligible patients, there is a trend towards more maintenance therapy given for the lower risk group patients, while in the transplant ineligible patients, maintenance therapy tends to be given for the higher risk group patients. However, the percentage remains small (less than 40%) in all groups. Maintenance therapy has OS and PFS1 benefit for the transplant ineligible patients, especially for the higher risk group patients. There is, however, no OS, PFS1, or PFS2 benefit observed for the transplant eligible patients. We plan to expand our study by collaborating with other Asian institutions to evaluate more patients. [Display omitted] DisclosuresChng:Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Aslan: Research Funding; Merck: Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.

TCT-238 Comparing 3 year outcomes between medical therapy and percutaneous revascularisation for the surgically ineligible cohort.

TCT-238 Comparing 3 year outcomes between medical therapy and percutaneous revascularisation for the surgically ineligible cohort.

Abstract P1-11-02: A comparison of models (physician, the Van Nuys prognostic index, the Memorial-Sloan-Kettering Cancer Center DCIS nomogram)to predict ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) of the breast after breast-conserving surgery failed to replicate results of the oncotype DCIS recurrence score

Abstract Purpose: To compare ipsilateral breast event (IBE) risks in patients with DCIS of the breast post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index (VNPI) studies, the Memorial Sloan Kettering Cancer Center (MSK) DCIS nomogram, and the 12-gene DCIS Recurrence Score assay. Materials/Methods: 12-gene DCIS Recurrence Score of 91 DCIS lumpectomy cases were identified from our practice. Clinicopathologic factors (excluding DCIS score) were summarized for blinded review. 3 radiation oncologists independently estimated the 10-year IBE risk and rated the impact of age/menopausal status, tumor morphology, tumor span, and margin width. Corresponding VNPI and MSK nomogram estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated with univariate and multivariate analysis. Results: Median age was 60, 25% margins &amp;lt; 3 mm, 48% DCIS span &amp;gt; 10 mm, 48% would have been ineligible for E5194. All comparisons were initially examined for similarity (non-significant differences) and susequently tested for a significant correlation. In three possible physician comparisons only 1 (AA-CL) had similar IBE estimates and strong correlation (r=0.792). Comparison of physicians to either VNPI nomogram or MSK DCIS calculator had similar estimates with strong correlation in only 2 of 6 possible comparisons in the all cases and the E5194 eligible patient cohorts respectively; and in 1 of 6 comparisons in the E5194 ineligible cohort. The DCIS Recurrence Score showed no strong correlation in regard to similar IBE estimates for any comparisons including either physicians, VNPI nomogram or MSK DCIS calculator. Tumor size was highly correlated with all physician IBE estimates (r = 0.547 to 0.799), while margin size showed moderate to high inverse correlations (r = -0.324 to -0.619). All 3 physicians rated margin width as having the most impact on their IBE risk estimates, then tumor morphology and tumor span. Source of EstimateAll Cases (n = 91)E5194 Eligible (n = 47)E5194 Ineligible (n = 44)DCIS Score15.1%, 5.3 (14.0-16.2)14.2%, 4.8 (12.8-15.6)16.1%, 5.7 (14.3-17.8)MSK DCIS Nomogram (Rudloff et al., 2010)18.8%, 7.7 (17.2-20.4)23.4%, 18.6 (19.6-27.3)16.1%, 4.1 (14.9-17.3)21.7%, 9.4 (18.8-24.6)VNPI studies23.4%, 18.6 (19.6-27.3)15.6%, 15.5 (11.0-20.1)31.9%, 18.1 (26.4-37.4)AA18.9%, 14.1 (16.0-21.9)11.7%, 8.8 (9.1-14.3)26.6%, 14.7 (22.2-31.1)CL19.9%, 11.8 (17.5-22.4)14.5%, 6.6 (12.5-16.4)25.8%, 13.3 (21.7-29.8)DC26.8%, 13.9 (23.9-29.7)19.8%, 5.9 (18.1-21.6)34.2%, 16.1 (29.3-39.1) Conclusion: IBE risk estimates for this cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual physician estimates. Surgical margins and tumor size continue to factor prominently in physician decision algorithms. In our observations, neither the VNPI nomogram, MSK DCIS calculator nor physician IBE risk estimates have similar values with strong enough correlation to reliably replicate the DCIS Recurrence Score. Citation Format: Leonard C, Lei R, Antell A, Nowels M, Fryman S, Howell K, Dennis C. A comparison of models (physician, the Van Nuys prognostic index, the Memorial-Sloan-Kettering Cancer Center DCIS nomogram)to predict ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) of the breast after breast-conserving surgery failed to replicate results of the oncotype DCIS recurrence score [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-02.

Determinants of Treatment Eligibility in Veterans With Hepatitis C Viral Infection

PurposesThe objective of this study was to determine the percentage of veterans with active hepatitis C virus (HCV) infection who were deemed to be candidates for treatment and to identify factors associated with treatment ineligibility. MethodsThis was a multisite, retrospective cohort analysis of veterans with HCV infection within the Veteran Integrated Service Network 21. Patients evaluated between August and November 2015 who were viremic and not receiving HCV treatment were included in the analysis. Reasons for treatment exclusion were determined by an experienced clinician and recorded into a regional population management dashboard. Descriptive statistics were used to describe the population. The t test for normally distributed data, the Mann-Whitney rank sum test for data that failed normality testing, or the χ2 test were used to examine differences between the treatment eligible and ineligible cohorts. Generalized linear mixed-effects models were conducted to estimate patient outcomes relevant to various disease states and characteristics while controlling for interfacility variability. FindingsThe cohort included 1,003 veterans within 5 medical centers; 988 (98.5%) were male, and 625 (62%) had a fibrosis 4 score >3.25, indicating the presence of ALD. According to clinician classification, 478 (48%) were considered HCV treatment candidates, whereas 525 (52%) were determined to be treatment ineligible. The most common reasons documented by clinicians for treatment ineligibility included unstable or uncontrolled comorbidities (n = 118 [22.4%]), excessive alcohol use (n = 116 [22.1%]), and treatment refusal by the patient (n = 69 [13%]). On the basis of statistical modeling and reporting odds ratios (ORs) and 95% CIs, diagnoses of active alcohol use disorder (OR = 0.68; 95% CI, 0.47–0.98; P = 0.038), hepatocellular carcinoma (OR = 0.24; 95% CI, 0.13–0.47; P < 0.001), and palliative care status (OR = 0.21; 95% CI, 0.05–0.99; P = 0.049) were statistically associated with treatment ineligibility, whereas posttraumatic stress disorder (OR = 1.48; 95% CI, 1.01–2.18; P = 0.046) was associated with treatment eligibility. There were no statistically significant differences found for other psychiatric diagnoses or an encounter for homelessness. ImplicationsResults of this study indicate that a high percentage of patients may not be considered treatment eligible at initial clinical review. Within this veteran population, the presence of uncontrolled comorbidities and excessive alcohol use were the most commonly reported reasons for treatment ineligibility. On the basis of this analysis, processes could be established to address modifiable barriers to treatment, thus expanding the number of individuals receiving potentially curative therapy for HCV infection.

TCT-336 Percutaneous coronary revascularization versus medical therapy in a surgically ineligible cohort

The decision to revascularize patients referred for coronary artery bypass (CABG) who are unsuitable for surgery is normally made at a Heart Team meeting. The clinical outcomes in this important patient subset are not known and these decisions are not guided by robust data. We analyzed the outcomes

The Role of Medical Expenditure Risk in Portfolio Allocation Decisions.

Economic theory suggests that medical spending risk affects the extent to which households are willing to accept financial risk, and consequently their investment portfolios. In this study, we focus on the elderly for whom medical spending represents a substantial risk. We exploit the exogenous reduction in prescription drug spending risk because of the introduction of Medicare Part D in the U.S. in 2006 to identify the causal effect of medical spending risk on portfolio choice. Consistent with theory, we find that Medicare-eligible persons increased risky investment after the introduction of prescription drug coverage, relative to a younger, ineligible cohort. Copyright © 2016 John Wiley & Sons, Ltd.

29 Outcomes of PCI versus medical therapy in a surgically ineligible cohort from a single centre

Introduction There are limited data describing outcomes in patients who have been turned down for surgical revascularisation (CABG) on the basis of prohibitive risk. Methods We analysed cardiovascular outcomes (composite major adverse clinical event rate, MACE: all cause mortality; cardiac death, myocardial infarction, MI; repeat revascularisation; and stroke) in a retrospective cohort of patients turned down for elective CABG who were treated with PCI or medical therapy in a single centre over a 4 year period. Results Higher rates of cognitive impairment, chronic total occlusion, peripheral vascular disease (PVD) and atrial fibrillation were seen in the medical treatment group (n = 117). There was no difference between MACE rates in the PCI (n = 131) and medical groups at 30d however a significant difference emerged in MACE at 1 year, 2 year and 3 years due to a reduction in all cause death, cardiac death and MI in the PCI group. There was no difference between MACE rates in the high SYNTAX tertile, unless cases where residual SYNTAX was greater than 22 were excluded from the analysis. Independent predictors of MACE within the PCI group were SYNTAX score and diabetes, whereas peripheral vascular disease, haemodialysis and left main involvement were all associated with negative outcomes in the medical group. Conclusion Our data suggests a benefit from PCI revascularisation in patients ineligible for surgery at 1 year and a MACE-free survival benefit from PCI up to 3 years in patients within low and intermediate SYNTAX tertiles compared to medical therapy.

Abstract P5-08-07: Appropriate use of the 21-gene recurrence score (RS) assay across Michigan

Abstract Background: The 21-gene RS assay is used to assess prognosis and to predict response to adjuvant chemotherapy in patients with early stage hormone receptor positive, Her2 negative invasive breast cancer. The National Comprehensive Cancer Network (NCCN) first recommended consideration of testing of appropriate patients with the RS assay in 2008. We examined trends in the use of testing with the RS assay in hospitals across Michigan from 2006 through 2013 using data from the Michigan Breast Oncology Quality Initiative (MiBOQI), a Blue Cross Blue Shield of Michigan/Blue Care Network-sponsored quality initiative. Methods: Demographic, pathologic, and treatment data for women with breast cancer treated at all 25 hospitals participating in MiBOQI were abstracted from the medical record. Patients were excluded if they had stage 0 or IV disease at diagnosis, received neoadjuvant therapy, had bilateral breast cancer, or had a prior history of breast cancer. The primary outcome was the percentage of patients eligible for testing according to NCCN criteria (version 2010) who underwent testing with the RS assay. Analyses were performed using the statistical software R, Version 3.0.1. Results: Of the 18,046 patients in the MiBOQI Registry from 2006-2013 who met inclusion and exclusion criteria, 7133 (39.5%) met the NCCN criteria for testing (eligible). The rate of testing increased from 2006 to 2013 in both the eligible and ineligible cohorts, and varied by site. 21-Gene Recurrence Score (RS) Testing in MiBOQI, 2006-2013FactorEligible (n=7133)Ineligible (n=10913)Tested with RS assay3920 (55.5%)1424 (13.0%)Testing rate in 200643.8%7.3%Testing rate in 201362.3%19.6%Testing by site, 2006-2013 (range)35.8% - 73.3%6.8% - 26.2% Testing of the eligible cohort was statistically significantly associated with younger age, lower tumor grade, and lack of nodal involvement. Overall, 73.4% of patients whose tumors were tested with the RS assay met the NCCN criteria for testing and were deemed appropriately tested. This rate of appropriate testing ranged from 60.8% to 85.4% across sites. Of all patients who underwent testing, 498 (9.3%) had 1 or more positive lymph nodes (&amp;gt;0.2 cm). Receipt of chemotherapy was lower in eligible patients who were tested compared to those not tested (25.5% vs 29.9%, p&amp;lt;0.001). Of the 2387 eligible patients with RS &amp;lt; 18, 117 (5.5%) received chemotherapy, which ranged from 0% - 13.6% across the 25 sites. Of the 341 patients with RS &amp;gt; 30, 56 (9.8%) did not receive treatment with chemotherapy, which ranged from 0% - 50% across the sites. Of the 1192 patients with RS 18-30, 502 (45.7%) received chemotherapy, ranging from 14.5% for RS 18 to 72.5% for RS 30. Conclusions: In sites across Michigan the majority of patients whose tumors were tested with the RS assay were in accordance with the NCCN guidelines, although there was considerable variability across sites. The rate of testing for patients who do not meet the NCCN criteria is increasing. There is very low inappropriate use of the recurrence score for making chemotherapy treatment decisions. Citation Format: Ali HY, Munir K, Braun T, Griggs JJ, Silver SM, Gorski DH, Breslin TM, Henry NL. Appropriate use of the 21-gene recurrence score (RS) assay across Michigan. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-07.