Vulnerable Pts Research Articles

COVID-19 vaccination in patients with cancer: Results from survey based observational study.

e18897 Background: COVID‐19 (C19) disproportionately affects those with comorbid medical conditions, leading to significantly higher mortality rate. Cancer(ca) is a well-studied risk factor for developing severe C19 disease. However, ca patients (pts) were largely excluded from clinical trials evaluating the safety and efficacy of 3 FDA-approved C19 vaccines (vax). We aim to study this highly vulnerable pts’ behavior and outcomes regarding C19 vax. Methods: A prospective and observational single center study. Adult ca pts (18-89 years) seen in clinics from Nov 2021-Sept 2022 were randomly interviewed using telephone surveys after a verbal consent. Type of ca and therapy data were collected from pts’ medical records. The survey included C19 disease status, vax status positive (vax+) or negative (vax-), reason for vax status, s.e, impact on ca Rx or ca progression. Our primary objectives were to assess the rate of vaccination in the adult ca pts and identify barriers to vaccination. Secondary objectives were determining factors associated with vax acceptance vs. hesitancy, identifying s.e of C19 vax, and effect of C19 vax on clinical outcomes in ca pts. Results: N = 170 [Males 82 (48.2%) and females 88 (51.8%)]. The median age was 65 years. Among 170 pts, 58.2% had solid malignancy, 40% had hematologic malignancy, and 1.8% had both solid and hematologic malignancy. Refer to Table 1 for outcomes data. Overall, 146 (85.9%) pts received C19 vax. C19 infection positive (C19+) in 49 (28.8%) pts. Of them 9 (18.4%) pts required hospitalization. The vax rate of prior C19+ pts was 73.5% compared to 90.9% in C19 infection negative (C19-) pts (p = 0.0013). Demographic factors were not significantly associated with vaccine uptake. A total of 50% pts developed s.e from vax. However only one patient (0.68%) reported a delay in ca treatment due to C19 vax and believed that vax affected the ca outcome. Conclusions: Our results demonstrate that majority of the ca pts were vaccinated against C19 and tolerated it well, with minimal side effects. Prior C19 infection significantly decreased vax uptake. Vaccination did not have notable adverse effect on ca outcomes. Oncologists should discuss the importance of C19 vax in the context of ca to avoid misconceptions and hesitancy. Clinical trial information: NCT04953065 . [Table: see text]

Characterizing the digital divide in a diverse cohort of African American (AA) patients (pts) with prostate cancer (PCa).

e18571 Background: We assessed pts’ self-reported access and ability to use a computer (C) and/or smart phone as part of a larger study exploring treatment decisions in a diverse group of AA PCa pts. Methods: Face-to-face interviews were conducted in a prospective cohort of 152 newly diagnosed early-stage AA PCa pts at Grady Memorial Hospital and the Atlanta Veterans Administration Hospital. Pts were asked whether they had access to a C, whether they had a C in their home, and whether they knew how to use a C. The questions were also asked about smart phones with Internet access. Demographics were collected including income, education (ed), and health literacy (lit) measured with the Rapid Estimate of Adult Literacy in Medicine (categorized as ≤ Grade (Gr) 3; Gr 4-6; Gr 7-8; and high school (HS)). Fisher’s exact test and logistic regression were employed to identify variables associated with the ability to use a C or smart phone. Due to the hypothesis generating, exploratory nature of the current analysis, no adjustments were made for multiple comparisons. Results: Age ranged 44-81. Annual income categories ranged from <$10,000 to >$76,000. Ed ranged from 4 years to 20. Most pts, 62%, had low health lit (< Gr 7-8) but 38% had adequate health lit (HS). In the lowest categories of each variable, more pts had access to a smart phone or C than had a smart phone or C at home, which in turn was greater than the number of pts who knew how to use a smart phone or C. In the lowest categories of each variable, more men knew how to use a smart phone than a C. Of 72 men with some college ed or higher, 90% or more had a smart phone or C and knew how to use them compared with 67% (39/58) with HS ed and 50% (11/22) with < HS ed who knew how to use a smart phone (p < 0.001), and 55% (32/58) with HS ed and 27% (6/22) with < HS ed who knew how to use a C (p < 0.001). Although ~ 90% of pts with income <$25,000 annually had access to smart phones or Cs, 72% (46/64) knew how to use a smart phone (p = 0.016) and just 56% (36/64) knew how to use a C (p = 0.004). Among pts reading at < Gr 4-6, 62% (23/37) knew how to use a smart phone (p = 0.006) and only 43% (16/37) knew how to use a C (p < 0.001). In multivariate logistic models predicting knowledge of how to use Cs or smart phones including the covariates education, income, health lit, and age, education remained a significant predictor of knowledge. Compared to men with < HS ed, men with some college ed or higher were more likely to know how to use a C (OR 77.1, 95% CI 13.8-689, p < 0.001) and were also more likely to know how to use a smart phone (OR 23.0, 95% CI 4.7-176, p < 0.001). Conclusions: Between 28-50% of pts with < HS ed, annual income < $25,000, and < Gr 4-6 health lit do not know how to use a smart phone. Between 44-73% of pts with < HS ed, annual income < $25,000, and < Gr 4-6 health lit do not know how to use a C. Presuming that pts can use the Internet through a C or smart phone to participate in cancer care and research may exacerbate health disparities for the most vulnerable pts. Clinical trial information: NCT03322891 .

COVID-19 vaccination behavior and outcomes in patients with genitourinary cancer in comparison with other cancer types.

134 Background: Cancer(ca) and old age are risk factors for developing severe COVID-19 (C19+) disease, related morbidity and mortality. These patients (pts) were excluded from clinical trials evaluating the safety and efficacy of 3 FDA approved C19 vaccines (vax). Genitourinary (GU) ca-prostate, bladder and kidney ca contribute to the majority of non-skin ca and median age of these pts range from 65-75 yrs. We aimed to study these highly vulnerable pts behavior and outcomes regarding C19 vax in comparison to non-GU ca pts (18-89 years). Methods: A prospective and observational single center study. Adult ca pts seen in clinics from Nov 2021-Sept 2022 were randomly interviewed using telephone surveys after a verbal consent. Type of ca and therapy data were collected from pts’ medical records. The survey included C19 disease status, vax status positive (+) or negative (-), reason for vax status, side effects (s.e), impact on ca Rx or ca progression. Data was entered on REDCap. The primary end point was rate of vaccination in adult ca pts. Secondary end points were to quantify C19 vax acceptance vs. hesitance, identify s.e of C19 vax and effect of C19 vax on outcomes in GU and non-GU Ca pts. Results: N=172; GU ca 21 (12.2%) and non-GU ca 151 (87.8%). Among GU ca pts- 9 had prostate ca, 7 had bladder ca and 5 had renal ca. C19+ in 4 (19%) GU and 45 (30.2%) non-GU pts. GU pts: 90.5% received C19 vax (Pfizer 47.6%; Moderna 42.9%, J & J 0%); 9.5% were not vaxed. Non-GU pts: 85.2% received C19 vax (Pfizer 39.1%; Moderna 43%, J & J 2.6%); 14.8% were not vaxed. The top 3 risk factors for serious C19+ were age >65yr (76.2%), heart disease (61.9%) and BMI>30 (42.9%) in GU ca pts and age >65yr (46.4%), BMI>30 (35.1%) and smoking (19.9%) in non-GU ca pts. The top 3 reasons for C19 vax (+) in GU ca pts: protection against C19+ for self (81%), for others (47.6%) and provider recommendation (38.1%). The main reasons for vax hesitancy in C19 vax (-) GU ca pts: concern for allergy to the vax (4.8%) and prior C19 infection (4.8%). The common s.e of C19 vax reported in GU ca pts were injection site inflammation (19%), headache (4.8%), muscle/body aches (4.8%) but no lymphadenopathy. None of GU ca pts reported delay in Rx or progression of the disease due to C-19 vax. Conclusions: C19 vax were overall well tolerated and did not impact ca outcomes in pts with GU malignancies. Oncologists should discuss the importance of C19 vax in the context of ca. Clinical trial information: NCT04953065 . [Table: see text]

Vulnerable patients with metastatic colorectal cancer in a real-world setting: A multicenter retrospective study.

114 Background: Several guidelines recommended less intensive chemotherapy for vulnerable patients (pts) with metastatic colorectal cancer (mCRC). However, data in a real-world setting are insufficient particularly for second- or later-line therapies. Methods: This is a multicenter retrospective study of vulnerable pts who were defined to be intolerant to intensive therapy. Vulnerable pts with unresectable mCRC who received vulnerable regimens fluoropyrimidines (FP) with or without biologics, reduced-dose doublet regimens with or without biologics, and anti-epidermal growth factor receptor (anti-EGFR), as first-line therapy between June 2015 and December 2018 were included. Results: A total of 210 pts from 15 Japanese hospitals were enrolled. Their median age, 78 years (range 28-90); male, 57%; ECOG PS 0/1/2, 28/51/21%; right-sided primary tumors, 35%; primary tumor resection, 76%; RAS mutant, 51%. Intolerance to intensive therapy was attributable to older age in 69% of pts, poor PS in 17%, liver and/or renal failure in 24%, and concomitant disease in 30%. First-line regimens such as FP with or without biologics were given to 68%, reduced-dose doublet regimens with or without biologics to 24%, and anti-EGFR monotherapy to 8%. For all pts, the median time to treatment failure (TTF) and overall survival (OS) were 7.6 and 21.4 months, respectively. The response rate (RR) was 31% and the disease control rate was 73%. Despite having a higher RR in doublet regimens with or without biologics, there were no survival differences between FP and doublet regimens (RR 26% vs. 45%, p = 0.03; median TTF 8.2 vs. 7.1 months, p = 0.22; and median OS 23.0 vs. 21.7 months, p = 0.37). Multivariate analysis revealed that ECOG PS2, older age (≥ 80), the presence of ascites, and the number of metastatic sites ≥ 2 were significantly associated with worse OS. Following first-line therapy failure in 195 pts, 74 (38%), 24 (12%), and 13 (7%) pts received vulnerable regimens, full-dose doublet regimens with or without biologics (fit regimens), and other regimens, respectively, as second-line therapy. The median TTF and OS were 4.4 and 13.7 months in vulnerable regimens and 2.6 and 11.7 months in fit regimens, respectively. In 84 pts (43%) who received best supportive care (BSC), the median OS was 3.5 months. Following second-line therapy failure in 84 pts who underwent vulnerable regimens as second-line therapy, third-line chemotherapy was administered to in 42 pts with a median OS of 13.7 months. Conclusions: The efficacy of first-line therapy for vulnerable pts in a real-world setting was comparable to previous studies. Second-line therapy demonstrated clinically significant antitumor activity. Nonetheless, the number of patients who received second- or later-lines chemotherapy was low, and survival in pts who received BSC was dismal.

Demographic and laboratory determinants of humoral immune responses and impact of different anti-SARS-CoV-2 vaccine platforms in patients with cancer: A systematic review and meta-analysis.

1543 Background: Patients (pts) with cancer have increased mortality from COVID-19 and their vaccination is crucial to prevent severe infection. We aimed to identify demographic and laboratory determinants of humoral immune responses to COVID-19 vaccination in pts with cancer and investigate differences in responses based on the vaccine platform. Methods: We searched for records in PubMed, Embase, and CENTRAL up to 28/09/21, as well as conference proceedings from ASCO and ESMO 2021. We included studies of pts ≥16 yr with a cancer diagnosis, who were vaccinated against SARS-CoV-2. Studies were excluded if ≥10% of the participants had other causes of immunosuppression or baseline anti-SARS-CoV-2 spike protein antibodies (Ab)/previous COVID-19 (PROSPERO ID: CRD42021282338). For this subgroup analysis of studies that reported a proportion of pts with cancer and positive Ab titers at any timepoint following complete vaccination, a random-effects model was used to estimate the humoral response rate (HRR) with 95% confidence intervals (CI). Results: We included 64 records, reporting data from 10,511 cancer pts. The HRR in the overall population and by subgroup are shown in Table. Elder patients with hematologic cancers (59%, CI 47-70%, N = 667) and patients with lymphopenia (50%, CI 25-75%, N = 111) or hypogammaglobulinemia (36%, CI 19-57%, N=226) were the subgroups with lower HRR. Male (77%, CI 69-84%, N = 2,659) and Asian (84%, CI 54-96%, N = 37) pts showed a trend to lower HRR when compared with females and other races, respectively. Pts vaccinated with mRNA vaccine platforms (79%, CI 74-83%, N = 9,404) had numerically higher HRR than those receiving the adenovirus vaccines (28%, CI 19-40%, N = 74). Conclusions: This study highlights demographic and laboratory determinants of weaker immune responses to SARS-CoV-2 vaccination, permitting better identification of more vulnerable pts. Despite the small number of pts included receiving adenovirus vaccines, these data also suggest prioritizing mRNA platform vaccination in pts with cancer. [Table: see text]

863P - Cabazitaxel for octogenarian patients with metastatic castration-resistant prostate cancer (MCRPC)

BackgroundCabazitaxel (CAB) was marketed in 2012 in Italy, based on overall survival (OS) benefit demonstrated on the TROPIC study in mCRPC post-docetaxel. The efficacy and tolerability of CAB is overlapping in all age groups, though for very elderly patients (pts) it has never really been verified. MethodsWe conducted a retrospective, observational real-life study in 57 octogenarian pts, treated with CAB in eleven Italian cancer centers from 2012 to 2018. Feasibility of treatment has been investigated by duration of treatment and its tolerability. Duration of treatment and toxicity profile were also evaluated according to </≥ 85 years, ECOG performance status (PS) </≥ 2 and comprehensive geriatric assessment (CGA) questionnaire. ResultsThis retrospective cohort included 57 mCRPC pts (median age 83.5 years; 21% aged over 85 years), 24% with exclusive bone metastatic disease, 50% with high-volume bone disease, 15% with high volume bone disease and visceral disease. Thirty-nine (68%) received the CGA questionnaire assessment, 34 resulted fit and 5 vulnerable. Ten (14%) had an ECOG PS≥2, 9% received CAB as second-line, 23 (40%) as third-line, 29 (51%) as forth or more line. CAB was administered at 25mg/sqm in 30 (52%) pts, and 20mg/sqm or adapted schedules in 27 (48%). These latter schedules were adopted mainly in the subgroups with age > 85 years (75%), PS≥2 (87.5%) and vulnerable according CGA questionnaires (100%). The median duration of treatment with CAB in all pts was 4.8 months, range 1-19 months (mo); 4.5mo in those aged > 85 years, 4.4mo in the vulnerable pts and 3.5mo in pts with PS≥2. The most represented grade 3-4 toxicity in the whole cohort were neutropenia (14%) and diarrhea (10.5%). Six patients (10.5%) drop out the treatment for significant toxicities: 3 febrile neutropenia G4, 2 diarrhea G4 and 1 severe cardiotoxicity, 5 (83%) of these pts received the 25mg/sqm schedule, and 4 pts (67%) aged between 80-84 yeras with ECOG PS=0 did not performed the CGA assessment before treatment. One death due to intestinal perforation non-clearly treatment-related was reported. ConclusionsOctogenarian patients may be treated with CAB with the 20mg/sqm regimen associated with less treatment interruptions. The CGA could contribute to better select pts. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

997PD - Validation of the geriatric vulnerability score (GVS) in older ovarian cancer (oOC) patients: An analysis from the GCIG-ENGOT-GINECO EWOC-1 study

BackgroundThe GINECO previously developed the GVS to identify geriatric vulnerability in oOC pts (Falandry, 2013). The derivation cohort was EWOT-3 database of 111 oOC pts treated with first line carboplatin. The GVS combines albumin (≥ or<35g/l), lymphocyte (< or≥1x109/L) levels, and activities of daily living (ADL; ≥ or<6), Instrumental ADL (≥ or<25), HADS (< or≥14) scores. With a cut-off ≥3, GVS delineated a population with significantly decreased OS (HR(95%CI)=2.94 (1.79–4.84), P <.0001). EWOC-1 international study included an external validation of the GVS as a secondary endpoint. MethodsPts ≥70 yrs diagnosed with FIGO stage III/IV epithelial OC and no organ failure were screened for GVS. Those with GVS≥3 were proposed EWOC-1 randomized trial, evaluating 3 treatment regimens in the vulnerable pts. Other pts’ data were collected in the “EWOC-1 registry”. External validation of GVS was performed in the whole population (V1), in the EWOC-1 registry subgroup (V2), and in the subgroup of pts treated with carboplatin paclitaxel regimens (V3). Cross-validation analyses (calibration, discrimination, and performance analysis) were performed according current recommendations (Steyerber, 2014). ResultsFrom 12/2013 to 11/2018, 447 elderly patients were included, 120 (27%) in EWOC-1 trial and 327 in EWOC-1 registry (V1: n=447, V2: n=327, V3: n=324). Patients’ cancer characteristics were similar in the validation cohorts compared to the derivation one. Median follow up was 22mo; missing values were limited (<2%). According the maximum likelihood analysis, the risk ratio of death according GVS score in V1 was (ref=0): 1: 1.8 (p=.029); 2: 2.4 (p<.001); 3: 4.1 (p<.001); 4: 5.5 (p<.001); 5: 9.1 (p<.001). Whatever the validation cohort, GVS≥3 significantly segregated two groups with different OS (median, in mo): V1 (13.2 vs 40.8; HR=2.8 (2.2,3.7), p<.001), V2 (11.9 vs 40.8, HR=3.5 (2.5,4.9), p<.001); V3 (18.1 vs 43, HR=2.6 (1.9,3.7), p<.001). ConclusionsGVS provides a reproducible and robust prediction model of vulnerability in oOC pts, independent of geographic and historic effect (V1), as well as treatment patterns (V3), validated on an international population. Clinical trial identificationPROTOCOL EWOC-1 - ENGOT OV-23 - 2013-000266-11. Legal entity responsible for the studyCentre Hospitalier Lyon Sud. FundingHospital Clinical Research Program (PHRC). DisclosureD. Lorusso: Honoraria (self), Honoraria (institution), Advisory / Consultancy: MERCK; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Tesaro; Officer / Board of Directors, Spouse / Financial dependant, Non-remunerated activity/ies: GCIG. A. Floquet: Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: Roche. O. Tredan: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): BMS; Honoraria (self): MSD. E. Pujade-Lauraine: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder /: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time e: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Genmab; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Incyte; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Pfizer. C. Falandry: Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self): MSD oncology; Honoraria (self): Teva; Honoraria (self): AstraZeneca; Honoraria (self): Baxter; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (institution): Chugai Pharma; Honoraria (institution): Pierre Fabre; Honoraria (institution): Astellas Pharma. All other authors have declared no conflicts of interest.

Patients’ understanding and adherence to oral anti-cancer medication (OAM): Results of an institutional pilot study.

e18280 Background: Advancements in biopharmaceuticals have led to increasing availability and use of OAM. While oral medications allow patients (pts) to receive treatment at home, OAM use introduces new challenges related to prescription filling, monitoring for and reporting of side effects, safe medication handling, and adherence. We assessed understanding of and adherence to OAM in pts vulnerable to these home-based challenges. Methods: This 2018 pilot study defined vulnerable pts based on spoken language (Chinese), older age (≥65 yrs), and public insurance ( &lt; 65 yrs). All pts had a cancer diagnosis, had been taking an OAM, and received prescriptions through the hospital’s specialty pharmacy. Prior to a clinic visit, pts completed patient-reported measures about OAM taking and handling. Clinical characteristics were extracted from medical records; medication information was extracted from pharmacy records. The study team’s specialty pharmacist (DH) classified patient-reported responses about OAM taking (days per week, times per day, special instructions) and handing (handling, storage, disposal) as adequate or inadequate. OAM regimens were classified by complexity based on number of drugs and schedule. Results: Of 61 eligible pts, 55 participated (90%). Mean age was 68 yrs (SD 12) and 53% were female. Pt subgroups were: 27% Chinese, 64% ≥65 yrs, and 9% &lt; 65 yrs with public insurance. 33% had solid tumor and 67% had hematologic malignancy; tyrosine kinase inhibitor was the most OAM type (42%). 49% of pts were on front-line therapy and overall median time on OAM was 1 year (Q1 0.4, Q3 1.7). Adequacy of OAM taking (30%) and handling (15%) were low; only 15% had adequacy in both. Pt subgroup and regimen complexity did not vary by adequacy of OAM taking or handling. Patient-reported adherence was high 5.4 (SD 1) (possible range 1-6) and did not vary by adequacy of OAM taking or handling. Conclusions: Understanding of how OAM should be taken and handled in a group of vulnerable pts was strikingly low and did not align with pts’ self-reports of adherence. Future interventions are needed to ensure that pts understand how to safely take and handle OAM, thereby optimizing their therapeutic potential.

Survival Differences Among Patients (pts) with Acute Myeloid Leukemia (AML) Treated with Allogeneic Hematopoietic Cell Transplantation (HCT) Versus Non-HCT Therapies: A Large Real-Time Multi-Center Prospective Longitudinal Observational Study

Introduction: Survival rates continue to improve after allogeneic HCT (Gooley et al, NEJM, 2013). Population-based studies also indicate overall improvement in survival of older (60-80 years old) AML patients (pts) (Bower, Blood Cancer Journal, 2016). Yet, only a small minority (6%-8%) of them receive HCT (Medeiros, Ann Hematol. 2015). Given these potentially incongruent findings and the changing face of survival in AML, we designed the first prospective multi-center longitudinal study dating from first presentation of adults with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We compared survival according to whether or not pts received HCT at later time points. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including activities of daily living (ADL); frailty; geriatric assessment including cognition; QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale, ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. We used time-dependent Cox regression analyses to identify baseline and time-dependent risk factors associated with mortality in the overall population. The factors identified as significantly associated with mortality (p Results: Median follow-up was 16.8 months (range 0.1-52.4). In the initial multivariate analyses, the following were identified as significantly associated with an increased risk of mortality (Table 2): HCT-CI scores ≥5 (p Survival after HCT was 58% at 2-years. Initial unadjusted analyses showed significantly lower risks of mortality in association with receiving allogeneic HCT (p=0.0003). These findings were similar in pts with intermediate (p=0.0005) or unfavorable (p However, in the adjusted models, the advantage of HCT in reducing mortality rates was lost both in the overall population (p=0.21, see figure) as well as in the other groups (p>0.54, 0.40, and 0.51, respectively, Table 3). Formal tests of interactions (Table 3) showed no statistically compelling evidence that the association of HCT and mortality varies with respect to the timing of mortality or to the underlying ELN risk. Conclusions: In a prospective observational study, adjusting for key AML-specific and pt-specific variables negated the observed benefit of HCT over non-HCT therapies in reducing mortality rates among AML pts. Our results might reflect 1) improvement in supportive care and non-HCT therapies, 2) a relatively high non-relapse mortality early after HCT and the need for longer follow-up to demonstrate an adjusted benefit of HCT, and 3) the high selectivity of the transplant eligibility process, as we accounted here for variables that are often ignored in "genetic assignment" randomized studies (i.e. comorbidities and function). New randomized trials are needed; however, these trials have to be more inclusive of vulnerable pts and measure pt-specific variables. Trials focusing on reducing burden of comorbidities, frailty and poor function are needed alongside trials to treat AML with or without HCT. Disclosures Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Shami:JSK Therapeutics: Employment, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; Baston Biologics Company: Membership on an entity9s Board of Directors or advisory committees; Lone Star Biotherapies: Equity Ownership; Pfizer: Consultancy. Rizzieri:Teva: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Arog: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Novartis: Consultancy; Gilead: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Wang:Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Alexion: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Otsuka: Consultancy. Sekeres:Opsona: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Opsona: Membership on an entity9s Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

A phase III trial to confirm the superiority of S-1 adjuvant chemotherapy for vulnerable elderly patients with pathological stage II/III gastric cancer after curative resection: JCOG1507 (BIRDIE).

TPS196 Background: Base on the ACTS-GC trial, adjuvant chemotherapy with S-1 at a dose of 80 mg/m2/day (4 weeks on and 2 weeks off, repeated for one year) is the standard care for stage II/III gastric cancer (GC) patients (pts) after D2 gastrectomy. As Japan has the most aged population in the world, the actual number of elderly GC pts is still increasing. While elderly pts population is heterogeneous and is conceptually composed of “fit”, “vulnerable” and “frail” pts, full-dose adjuvant chemotherapy tends to be given to fit elderly pts in clinical practice. However, it has not been determined yet whether S-1 should be administered to vulnerable pts over 80. Actually, according to the questionnaire survey conducted on 58 institutions of Stomach Cancer Study Group of Japan Clinical Oncology Group, S-1 was administered on only 15% to stage II/III pts &gt; = 80 years old suggesting that surgery alone is generally considered as community standard for vulnerable pts. It is an urgent need to establish the standard adjuvant treatment of the vulnerable elderly GC pts. Methods: The study is designed to confirm the superiority of S-1 treatment group over surgery alone group focusing on vulnerable &gt; = 80 years old pts in stage II / III GC after curative resection. The “vulnerable” is defined in this study based on the three factors [creatinine clearance (Ccr), weight loss, type of surgery] considered to have the most influence on compliance of S-1, that is Ccr &gt; = 30ml/min, weight loss &lt; 15% and total gastrectomy, or 80 &gt; Ccr &gt; = 30ml/min, weight loss &lt; 15% and other than total gastrectomy. Initial dose was reduced by 1 rank from the standard dose. The primary endpoint is overall survival (OS) and the secondary endpoints are relapse free survival, time to treatment failure, treatment continuity, relative dose intensity and adverse events. We assume expected 3-year OS in surgery alone arm will be 55% and S-1 treatment will improve the survival by more than 10%. 370 pts are required to provide 75% of power and 5% one-sided alpha error, with 4 years accrual and 3 years of follow up period. The trial has started from January 2017. Clinical trial information: UMIN000025742. Clinical trial information: 000025742.

Development of a geriatric vulnerability score (GVS) in elderly advanced ovarian cancer (AOC) patients (pts) treated in first line: A prospective GINECO trial.

9079 Background: Two previous prospective GINECO studies in elderly patients have underlined the prognostic value of geriatric covariates (Co) on overall survival (OS) (Freyer G., et al. Ann Oncol. 2005 and Tredan O, et al Ann Oncol 2007). Methods: This open prospective trial was designed to confirm the impact of geriatric Co including psycho-geriatric Co on OS of elderly pts (≥70) with stage III-IV AOC treated in first line with 6 courses of carboplatin AUC5/3weeks. Geriatric Co were tested for their impact on OS in uni- and multivariate analyses. The best fitting proportional hazard model (GVS) was developed with the inclusion of major (MaC) and minor Co (miC). Results: From 08/2007 to 01/2010, 111 pts were included in 21 centres. A majority of pts displayed characteristics of vulnerability: age (median:78, range: 70-93, ≥80:41%), PS≥2: 43%, ≥3 major comorbidities: 27%, ≥4 comedications: 69%, ADL score&lt;6: 55%, IADL score&lt;25: 75%, HADS≥15:37%. A total of 74% of pts, however, completed planned chemotherapy. Gr3-4 haematological toxicity was observed in 50% of pts (thrombocytopenia [27%], anaemia [19%], and neutropenia [30%]) and gr3-4 non-haematological toxicity was fatigue (16%), anorexia (13%) and infection (10%). Median OS was 16.2 months (95%CI[14-21]). MaC were: albuminemia&lt;35g/L; ADL score &lt;6; IADL score &lt;25 and miC: lymphopenia&lt;1G/L; HADS£14. The survival score=exp(0.320*Number [MaC] +0.354*Number[miC]) was validated upon a bootstrap analysis. Using a cutoff of 3, the simplified GVS score = Number[MaC] + Number[miC] discriminated two groups with significantly different OS :11.5 vs 21.7 months; HR=2.94; p&lt;10-4, but also treatment completion rates: 65.4% vs 82.1%; OR=0.41; p=0.04; severe adverse events (SAE): 52.7% vs 28.6%; OR=2.8; p=0.009 and unplanned hospital admissions: 52.8% vs 30.3% OR=2.6; p=0.02. Conclusions: The GVS identified a group of pts at high risk of severe toxicity, early treatment stopping, unplanned hospitalization and poor outcome. GVS provides a useful tool to identify vulnerable pts in future elderly AOC trials.

Biweekly liposomal pegylated doxorubicin in elderly women with advanced breast cancer: A prospective multicenter trial focusing on tolerability and cardiotoxicity.

1138 Background: To assess tolerability and activity of liposomal pegylated doxorubicin (PLD) in women older than 70 years with locally advanced or metastatic breast cancer within a multicenter prospective trial. Methods: All pts underwent Multidimensional Geriatric Assessment (MGA) and frail pts (dependence in Activities of Daily Living; three or more severe comorbidities, geriatric syndromes) were excluded. Normal cardiac function was required at baseline. Bi-weekly schedule of 20 mg/m2 was adopted. More than 12 doses were prescribed only to responsive pts. Results: From Feb 2006 to Sep 2009, 28 pts were enrolled, median age 77 yrs (range 70-93), 10.7% had locally advanced disease, 10.7% only bone metastases, 78.6% visceral involvement; 28.6% of pts had been pre-treated with one or more lines of chemotherapy for advanced disease. After MGA, 35.7% were deemed fit and 64.3% vulnerable. A mean of 7.2 doses were delivered (range 1 to 20), with an actual dose intensity of 8.9 mg/m2/week (range 5.2-10). Worst toxicity experienced by pts is outlined in table. No cardiac events were registered. Only 1 pt received both G-CSF and erythropoietin. Causes of treatment interruption were progression 46.4%, refusal/loss at follow-up 21.4%, toxicities 10.7%, other or ongoing 10.7%. RECIST response was obtained in 34.8% of 23 evaluable pts, 30.4% remained stable; with a median TTP of 4.4 mo (11 censored), and a median OS of 15.4 mo. Receiving full dose intensity vs <9 mg/m2/week did not impact on response (p=0.26) and progression (p=0.6), as well as MGA status (vulnerable vs FIT, p=0.65 for response, p=0.9 for progression). Conclusions: Biweekly PLD monochemotherapy is well tolerated in terms of hematological and cardiac safety both by fit and vulnerable pts, with an apparently fairly good response rate. Close follow-up of pts is recommended in order to monitor skin toxicity and avoid early refusal/loss at follow-up. Accrual is still ongoing. Toxicity according to CTCAE v3 Grade 1-2 Grade 3-4 Neutropenia 23% 0 Thrombocytopenia 5% 0 Anemia 18% 9% Palmar-plantar erythrodysesthesia 41% 9% Nausea/vomiting 32% 0 Mucositis 18% 9% Infection 0 5% No significant financial relationships to disclose.

A multicenter phase II randomized study of gemcitabine (G) weekly followed by erlotinib (E) after progression versus E followed by G after progression in advanced non-small cell lung cancer (NSCLC) in vulnerable elderly patients selected with a comprehensive geriatric assessment (CGA) (GFPC*0505).

e18002 Background: Elderly patients (pts) are a heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly G followed by E after progression versus E following by G after progression in vulnerable elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score (CS). Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received G 1,250mg/m2 days 1, 8, for a maximum of 18 weeks or until progression, followed by E until second progression (arm A) versus E in first line followed by G until second progression (arm B).Only vulnerable pts (without dependence for ADL and geriatric syndrome) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment, depression scale, nutritional risk, quality of life(QOL), ADL, IADL (Lawton), incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 95 pts (67 available today) were enrolled from Aug 2006 to Dec 2009. Patients: Male/Female 54/13, median age 78.1; PS 0/1/2:22/33/10, median co-morbidity (CS) 1.85 (1-3), median IADL score 3.48 (1-4), median global geriatric index: 17.7/20. Respectively for arm A and B, partial response was 18% and 7%, stable disease 18% and 27%, progressive disease 64% and 67%,TTP1 81 and 63 days, median survival 4.3 and 3.9 months. The main WHO grade 3/4 toxicity was anemia 12.5% and fatigue 12.5% in arm A and fatigue 28.6% and anemia 5.7% in B. Conclusions: Preliminary analysis suggests that either the G followed by E or E followed by G appears to have acceptable toxicity but moderate activity, comparable in terms of efficacy to prior data in this vulnerable elderly NSCLC pts population with significant co-morbidities. Our trial confirms the necessity to identify the better tools in CGA to distinguish frail pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Roche

A phase II study of an adapted CT with oxaliplatin (Oxa) and bolus 5FU in I-line treatment of metastatic CRC in elderly patients not eligible to FOLFOX

15124 Background: FOLFOX and FOLFIRI have been established to be an effective I-line CT for mCRC. Not all over 70-yrs old pts can receive infusional 5-FU because of cardiac comorbidity, refuse of infusional CT or vulnerability state at the comprehensive geriatric assessment (CGA). Till now no alternative schedules containing Oxa have been assessed in elderly pts. The aim of the present study was to evaluate the feasibility and activity of biweekly Oxa plus bolus 5FU and low dose LV as I-line CT. Methods: pts ≥70 yrs with measurable, chemonaive mCRC, ECOG PS ≤2, not eligible to infusional 5FU, fit or vulnerable at CGA (Balducci et al) received Oxa 85 mg/m2 on d 1 and 15, LV 20 mg/m2 plus bolus 5FU 500 mg/m2 on d 1, 8 and 15 every 28d. Study design was 1 stage, estimated sample size 34. Toxicity was the primary endpoint. Response was evaluated by CT-scan every 2 cy. Results: 35 pts, median age 74 (range 70–84) entered the study. Ten pts (28.6%) had cardiological comorbidities. Median number of comorbidities was 1.3 among 20 vulnerable pts, 0 among 15 fit pts. Toxicity according to CTC v 3.0 (see table), was not related to age or CGA. 46.7% of fit pts and 70% of vulnerable pts received < 6 cycles of CT because of toxicity (7 pts), PD (6 pts) or refuse (8 pts). Out of 28 valuable pts 10 PR were observed for an RR of 35.7% (95% CI 17.9–53.4%). Eleven pts had SD (39.3%) while 7 progressed during treatment (25%). After a median follow up of 29.3 mo 32 pts progressed or died, with a median PFS of 9.4 mo. Totally 24 out of 35 pts died, for a median OS of 16.3 mo. A clinical difference in terms of OS among 15 pts receiving II line CT and the other 20 receiving only best supportive care (13.9 vs 11.4, p=0.19 n.s.) was reported. Conclusions: Biweekly Oxa with bolus 5-FU is a safe and effective alternative in elderly pts not susceptible to FOLFOX because of refuse by pts or vulnerability at CGA. Toxicity Toxicities Grade 2 Grade 3 Grade 4 Number % Number % Number % Anemia 4 11.4 1 2.8 0 0 Neutropenia 3 8.6 3 8.6 1 2.8 Trombocytopenia 3 8.6 0 0 0 0 Diarrhea 2 5.7 5 14.3 1 2.8 Mucositis 2 5.7 0 0 1 2.8 Vomiting 2 5.7 1 2.8 0 0 Neurotoxicity 6 17.1 3 8.6 1 2.8 Fatigue 3 8.6 1 2.8 0 0 No significant financial relationships to disclose.