Median Number Of Systemic Therapies Research Articles

A meta-analysis of local-regional therapy (LRT) in liver metastases from genitourinary cancers.

e16606 Background: Liver metastases (Mets) from genitourinary cancers are difficult to treat and many of them are resistant to systemic therapy. Local-Regional Therapies (LRT) are becoming popular in treating Liver Mets. In this Meta-analysis, we analyze the outcomes of LRT for Liver Mets from Genitourinary Cancers. Methods: We searched PubMed, Google scholar for case reports, case studies, retrospective studies with patients who underwent LRT like Radiofrequency Ablation (RF), Chemoembolization (CE), Microwave Ablation (MA), Cryoablation for liver metastases for from Genitourinary Cancers including Prostate Cancer (PC), Testicular Cancer (TC) and Renal Cell Cancer (RCC). We also included 3 patients from Dignity Health Cancer Center, Phoenix, AZ. Results: Total number of patients in the study is 54, 3 of them from our Center. 39 are men and 15 are women. Mean and median age of the patients was 62.3, 65 years respectively. Number of patients with RCC, PC, TC are 43, 6, 5 respectively. 28 patients had CE, 23 had RFA and 3 had MA with the total number of procedures being 144, 41 and 5 respectively. Mean survival for all the patients is 62.7 months, mean survival for RCC, TC and PC are 68.9, 45.8 and 24.4 months respectively. Median number of systemic therapies received by the patients prior to getting LRT was 2 (range 1-4). We used RECIST criteria to quantify the benefit from LRT, 23 patients had Complete Response (CR), 6 had Partial Response (PR), 14 had Stable Disease (SD) and 8 had Progressive Disease (PD), there was no data for 2 patients. 43 patients had Clinical Benefit. We present a case of castration resistant metastatic PC from our facility. A 78-year man diagnosed metastatic PC in 2007 who had Prostatectomy, salvage radiation, intermittent androgen deprivation and Combined deprivation therapy. But his PSA continued to rise, flutamide was added. In 2017, he had liver metastasis, had RFA twice for 2 liver lesions and had CR. He continues to be on relugolix with good quality of life. Patients in the study are people with advanced metastatic cancer who underwent various systemic therapies like chemotherapy, radiation, immunotherapy and hormonal therapy prior to getting the LRT. LRT was done as the patients failed or did not tolerate systemic therapies. The mean survival for RCC patients in the study group is greater than the average survival of stage IV RCC, the lower mean survival for PC and TC can be explained by the limited number of this patient population in the study. Conclusions: Combination of LRT with systemic therapy for previously heavily treated Liver Mets from genitourinary cancers is a promising strategy for patients with otherwise poor prognosis. [Table: see text]

Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma.

The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.

Characterizing Outcomes in Visceral Cutaneous T-Cell Lymphoma: A Real-World Retrospective Study

Introduction: Visceral Cutaneous T-Cell Lymphoma (vCTCL) is a rare and understudied complication of CTCL. Visceral involvement is associated with a poor prognosis, with a median survival of less than 1.5 years. We aimed to assess clinical characteristics, treatment, and outcomes associated with vCTCL. Methods: We conducted a retrospective review of patients with vCTCL from a CTCL database of 656 patients seen at the Winship Cancer Institute at Emory University from 1990-2022. vCTCL was defined as stage 4B or M1 disease that was pathologically confirmed or clinically suspected. Clinical data collected from the electronic medical record included baseline demographics, disease characteristics, pathologic characteristics, laboratory values, and treatment patterns. Descriptive analysis was performed for covariates. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and univariable Cox regression analysis. Statistical analysis was performed using SAS with significance at the 0.05 level. Results: Twenty-six patients had vCTCL of which 42.3% were black and 57.7% were white. There was an even distribution among male (53.8%) and female patients (46.2%) [Table 1]. Median age at diagnosis of vCTCL was 58.5 years (47-66). Eight patients (30.8%) had ECOG PS ≥2. The most common diagnosis was mycosis fungoides (73.1%) and Sézary syndrome (11.5%), others being primary cutaneous anaplastic large cell (n=1), cytotoxic T cell (n=1), and gamma-delta T cell lymphoma variants (n=1). At the time of initial diagnosis, TNMB stage was 1B in 7 patients (33.3%), 2A/2B in 6 (28.6%), 3A in 2 (9.5%), 4A1/A2 in 4 (19%), and 4B in 7 (33.3%). Four patients (15.4%) had N2 involvement and 8 patients (30.8%) had N3 involvement. Eight patients had stage B2 disease (30.8%). Approximately half of the cohort had large cell transformation (LCT) with 61.5% having concurrent biopsy-proven LCT with visceral metastasis. Eleven patients (60%) had matched skin and blood TCR positivity. Twenty-three patients had biopsy-proven vCTCL with the most common sites being lung (42.3%), liver (19.2%), bone marrow (11.5%), and CNS (11.5%). Nine patients (34.6%) had at least 2 sites of metastases. Liver metastases were associated with a higher rate of subsequent disease progression (HR 3.29, p=0.031). Other metastases (23%) involving the thyroid, kidney, pleural or peritoneal compartments were associated with decreased survival (HR 8.91, p<0.001) and progression (HR 4.28, p=0.009). Median follow-up was 28.4 months (mo). The median time to visceral involvement from diagnosis was approximately 1 year. Nearly all patients (96.2%) received treatments after vCTCL diagnosis. Median time to first treatment of vCTCL was 2.3mo. Median number of systemic therapies after vCTCL diagnosis was 2. Two patients had complete response (7.7%) and one had partial response (3.8%) with the rest having progressive disease (88.5%). There was no difference in OS or PFS by race, and black patients had a trend toward improved outcomes. Median OS in black and white patients was 18.2mo and 11.4mo respectively (HR 0.5, p = 0.097, Figure 1). Median PFS in black and white patients was 8.7mo and 4.3mo respectively. Black patients had higher median lactate dehydrogenase levels at vCTCL diagnosis (p=0.018) and trended towards an earlier age at diagnosis (54 years vs 62 years) and a shorter time to metastasis (7.9mo vs. 13.3mo) but these factors were not associated with survival outcomes. Most patients received multi-agent chemotherapy (n=13), total electron beam therapy (n=11), and brentuximab vedotin (n=6). Black and white patients had similar time to first treatment and total number of treatments. White patients were more likely to receive combination chemotherapy (66.7% vs 27.3%, p=0.047). Two patients in our cohort had durable complete response to therapy. The first patient developed CNS metastases and achieved durable response with HD-MTX. The second patient had concurrent pulmonary vCTCL and LCT and developed durable response with allogeneic transplantation. Treatments, other demographic information, ECOG, histopathology, LCT were not associated with survival outcomes. Conclusions: Our analysis of a large CTCL cohort from a 30-year period confirms the rarity and poor outcomes in patients with visceral CTCL disease. More prospective studies and clinical trials are needed to guide treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Systemic treatment of advanced clear cell sarcoma: results from a retrospective international series from the World Sarcoma Network

BackgroundClear cell sarcoma (CCS) is a translocated aggressive malignancy with a high incidence of metastases and poor prognosis. There are few studies describing the activity of systemic therapy in CCS. We report a multi-institutional retrospective study of the outcomes of patients with advanced CCS treated with systemic therapy within the World Sarcoma Network (WSN).Materials and methodsPatients with molecularly confirmed locally advanced or metastatic CCS treated with systemic therapy from June 1985 to May 2021 were included. Baseline demographic and treatment information, including response by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, was retrospectively collected by local investigators. Descriptive statistics were carried out.ResultsFifty-five patients from 10 institutions were included. At diagnosis, the median age was 30 (15-73) years and 24% (n = 13/55) had metastatic disease. The median age at diagnosis was 30 (15-73) years. Most primary tumours were at aponeurosis (n = 9/55, 16%) or non-aponeurosis limb sites (n = 17/55, 31%). The most common fusion was EWSR1–ATF1 (n = 24/55, 44%). The median number of systemic therapies was 1 (range 1-7). The best response rate was seen for patients treated with sunitinib (30%, n = 3/10), with a median progression-free survival of 4 [95% confidence interval (CI) 1-7] months. The median overall survival for patients with advanced/metastatic disease was 15 months (95% CI 3-27 months).ConclusionsSoft tissue sarcoma-type systemic therapies have limited benefit in advanced CCS and response rate was poor. International, multicentre prospective translational studies are required to identify new treatments for this ultra-rare subtype, and access to early clinical trial enrolment remains key for patients with CCS.

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

Clinical Efficacy of Polatuzumab Vedotin in Patients with Relapsed/Refractory Large B-Cell Lymphoma after Standard of Care Axicabtagene Ciloleucel

Introduction. The outcome of patients with large B-cell lymphoma (LBCL) relapsing or progressing after anti-CD19 CAR T-cell therapy is dismal, and novel therapeutic strategies are needed. Polatuzumab vedotin (PV) is a CD79b-directed antibody-drug conjugate, approved by the FDA in combination with bendamustine and rituximab for the treatment of patients with LBCL who relapse or progress after at least 2 lines of systemic therapy. CD79b targeting is an appealing strategy after failure of anti-CD19 CAR T-cell therapy, but the activity of PV in this setting has not been investigated. Methods. This is a retrospective analysis of patients with relapsed/refractory LBCL after standard of care axicabtagene ciloleucel (axi-cel), and treated with standard of care PV at MD Anderson Cancer Center between 07/2019 and 03/2020. PV was given at the standard dose of 1.8 mg/kg IV every 3 weeks in all patients. PV was administered with rituximab, with or without bendamustine. Response to treatment and progression were defined according to 2014 Lugano criteria. Results. Eight patients were included in the analysis: median age was 54 (range, 41-70 years), 7 (87.5%) were male, and all had an IPI score &amp;gt; 3. Median number of systemic therapies before axi-cel was 3 (range, 2-7), and median number of systemic therapies between axi-cel and PV use was 1 (range, 0-3); 1 patient previously had autologous stem cell transplant (SCT), and 2 had allogeneic SCT. Three (37.5%) patients were primary refractory to axi-cel therapy, and median time from axi-cel to PV was 6 months (range, 1-12 months). All patients were biopsied at time of relapse after axi-cel, and in all cases lymphoma was CD19+ CD79b+ by immunohistochemistry/flow cytometry. At time of PV initiation, median absolute neutrophil count was 2.6 (range, 0.4-4.7 X109/L), median platelet count was 141 X109/L (range, 7-245 X109/L), median serum creatinine was 0.9 mg/dL (range, 0.5-1.5 mg/dL), and all patients had LDH above upper limit of normal. Median number of PV cycles was 2 (range, 1-3): PV was combined with rituximab in all patients but administered with bendamustine in only 3 (37.5%). No significant toxicity, prompting dose reduction or treatment discontinuation, was observed. A response was achieved in 4 (50%) patients, represented by partial remission (PR) in all cases, whereas 4 (50%) patients were refractory. All patients stopped PV, 6 (75%) because of progression, 1 (12.5%) to proceed to allogeneic SCT while in PR, and 1 (12.5%) to proceed to an immunotherapy clinical trial (despite absence of progression). After a median follow up of 29 weeks (95% CI, 16-31 weeks), all patients progressed/died, and median PFS was 5 weeks (95% CI, 2-8 weeks) (Figure). At most recent follow-up, 5 (62.5%) died, and median OS was 15 weeks (95% CI, 9-21 weeks)(Figure); causes of death included progression in 4 patients, and transplant-related complications in 1. Discussion. PV in combination with rituximab is safe but has limited and short-lasting activity in relapsed/refractory LBCL after anti-CD19 CAR T-cell therapy. These findings need to be confirmed in larger and prospective studies. The activity of PV, alone or in combination with novel drugs, for the treatment of patients with CD19-negative relapses after CAR T-cell therapy remains to be investigated. Figure Disclosures Westin: 47 Inc:Consultancy;Curis:Consultancy;Janssen:Consultancy;Novartis:Consultancy;Genentech:Consultancy;Juno:Consultancy;Kite:Consultancy;MorphoSys:Consultancy;Unum:Consultancy.Neelapu:Acerta:Research Funding;Takeda Pharmaceuticals:Patents &amp; Royalties;Pfizer:Other: personal fees;Unum Therapeutics:Other, Research Funding;N/A:Other;Novartis:Other: personal fees;Adicet Bio:Other;Legend Biotech:Other;Bristol-Myers Squibb:Other: personal fees, Research Funding;Merck:Other: personal fees, Research Funding;Kite, a Gilead Company:Other: personal fees, Research Funding;Incyte:Other: personal fees;Calibr:Other;Precision Biosciences:Other: personal fees, Research Funding;Allogene Therapeutics:Other: personal fees, Research Funding;Cell Medica/Kuur:Other: personal fees;Poseida:Research Funding;Celgene:Other: personal fees, Research Funding;Cellectis:Research Funding;Karus Therapeutics:Research Funding.

Treatment Patterns and Clinical Outcomes of Patients with Sézary Syndrome at Emory University

Introduction Sézary syndrome (SS) is an aggressive, leukemic subtype of cutaneous T-cell lymphoma (CTCL) with a median survival of 3-5 years. Approved therapies include skin-directed therapy, radiation, and systemic therapies such as chemotherapy, histone deacetylase (HDAC) inhibitors, interferon, extracorporeal photopheresis (ECP), and oral retinoids. There is no consensus first-line therapy for SS and there is limited data regarding prognostic biomarkers. We assessed treatment patterns, outcomes, and racial differences at our institution. Methods We performed a retrospective review of 62 patients at Winship Cancer Institute of Emory University from 1990-2020 with a confirmed diagnosis of SS. Clinical data collected from the electronic medical record included demographics, baseline laboratory values, disease characteristics, and therapy. Clinical outcomes were measured by overall survival (OS) and time to next treatment (TTNT). OS was measured from time of diagnosis to date of death or last follow-up. TTNT was defined as the number of months from the start of the first line of therapy until the initiation of the subsequent therapeutic regimen. Descriptive analysis was performed for each variable and a comparison between African American (AA) and white patients was performed using ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS and TTNT were generated for the whole cohort. A Kaplan-Meier curve was also generated to compare time from diagnosis to initiation of first systemic therapy stratified by race along with the log-rank p-value. The univariate association of baseline variables with OS and TTNT was assessed by Cox proportional hazards models and the multivariable analyses (MVA) were performed on variables that had p-value less than 0.05 on univariate analyses. Results Males made up (58.1%) of our patients and the median age at diagnosis was 65.9 years. Nearly one-half (45.2%) of patients were AA. The median Sézary count at diagnosis was 1320 cells/uL. The median time from diagnosis to first systemic therapy was 2.4 months and the median number of systemic therapies was 3.0. Information regarding systemic treatments received after diagnosis is presented inTable 1. The most common first-line systemic therapies were oral retinoids (43.5%), ECP (32.3%), and interferon (30.6%). HDAC inhibitors and total skin electron beam (TSEB) radiation were common treatments beyond first line (46.8% received HDAC inhibitors, 38.7% received TSEB), but were rarely used in the first-line setting. The median OS and TTNT were 3.1 years and 6.3 months, respectively(Figure 1). In MVA, elevated WBC and LDH were significantly associated with shorter OS (WBC HR: 1.05, 95% CI: 1.01-1.08, p=0.01; LDH HR: 1.003, 95% CI: 1.001-1.005, p=0.011) and shorter TTNT (WBC HR: 1.04, 95% CI: 1.002-1.08, p=0.041; LDH HR: 1.002, 95% CI: 1.001-1.004, p=0.048). In analysis by race, AA patients had a higher proportion of females compared to non-hispanic white patients (53.6% vs 28.1%, p=0.045). AA patients also had lower median hemoglobin at diagnosis (12.6 vs 14.3, p=0.036), higher median LDH at diagnosis (360 vs 232, p=0.002), and longer median time from diagnosis to first systemic therapy compared to non-hispanic white patients (3.17 months vs 2.14 months, p=0.039,Figure 2). Conclusions SS is an aggressive subtype of CTCL with no consensus first-line therapy and limited data on prognostic biomarkers. In our cohort, oral retinoids, ECP, and interferon were the most commonly utilized treatments in the first-line setting. Elevated WBC and LDH were significantly associated with both OS and TTNT which suggests that these may have value as prognostic biomarkers in SS. AA patients may have delayed time from diagnosis to starting systemic therapy and higher LDH at diagnosis. This data is hypothesis-generating and should be validated in larger, prospective studies. Disclosures Allen: Bayer:Consultancy, Other;Imbrium:Consultancy, Other;Research to Practice:Speakers Bureau;Clinical Care Options:Speakers Bureau;Curio Sciences:Honoraria.

Radiation Therapy for Refractory High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) is an aggressive disease with inferior outcomes. We sought to evaluate the efficacy of radiation therapy (RT) for patients with HGBL-DH/TH treated for gross disease. We identified 80 patients treated with RT between 2013-2019 for refractory diffuse large B-cell lymphoma. Patients with CNS disease were excluded. Eligible patients had fluorescence in situ hybridization (FISH) confirmed HGBL-DH/TH with gross disease at the time of RT (defined as positron emission tomography-computed tomography [PET-CT] five-point scale [5PS] of 4-5 or progression on CT). RT intent was palliative (disease excluded from the field), salvage (all known disease encompassed), or bridging (RT prior to chimeric antigen receptor [CAR] T-cell therapy). Progression free survival (PFS), overall survival (OS) and local control (LC) were defined from the last day of RT. LC was defined as the absence of in-field recurrence and censored at the time of last follow up, out of field progression, or death. The in-field overall response rate (ORR) was defined as combined partial response (PR) and complete response (CR) within the RT field. We identified 27 HGBL-DH/TH patients. The median age was 63.5; 78% had primary refractory disease after frontline chemotherapy. The median number of systemic therapies (ST) prior to RT was 2 (range [R] 1-4). Intent of RT was palliative in 33% (n = 9), salvage in 59% (n = 14) and bridging in 15% (n = 4). The median RT dose was 42.5 Gy (R 8-60); 59% received a dose of ≥ 40 Gy (n = 16). Concurrent ST was given to 37% (n = 10). ST after RT was administered to 48% (n = 13); 37% (n = 10) received CAR T-cell therapy after RT. The median follow-up was 12.1 months. There were 20 recurrences (74%) and 18 deaths (67%, all due to lymphoma). The 1-year PFS and OS rates were 22.2% and 32.2% respectively. LC evaluation was possible for 25 patients. While the initial in-field ORR was 88% (CR, n = 12, PR, n = 10), the 1-year LC rate was only 43.8% with 11 in-field recurrences in total, either in the absence (n = 2) or presence of out of field progression (n = 9). LC was not impacted by RT doses of ≥40 Gy (p = 0.62); the median RT dose for patients with local failure was 46.7 Gy (R 24-60). There was no difference in PFS according to RT intent (p = 0.56), RT dose ≥ 40 Gy (p = 0.57), receipt of concurrent ST (p = 0.14), or receipt of ST after RT (p = 0.34). Similarly, OS was not impacted by these factors. However, patients that received CAR T-cell therapy after RT had a trend towards improved PFS (p = 0.07) and superior OS (p = 0.04). Patients with refractory HGBL-DH/TH have a poor prognosis. While initial in-field ORRs are high, even with RT doses ≥40 Gy, in and out-of-field progression is common. CAR T-cell therapy can be effective in this population. RT with a short, hypofractionated course may be a useful tool to permit disease temporization while CAR T-cell therapy is pursued.

Outcome of Autologous Stem Cell Transplantation Following PD-(L)1 Based Salvage Therapy for Multiply Relapsed Patients with Classic Hodgkin Lymphoma

Outcome of Autologous Stem Cell Transplantation Following PD-(L)1 Based Salvage Therapy for Multiply Relapsed Patients with Classic Hodgkin Lymphoma

Abstract P1-12-07: Phase Ib/II single-arm trial evaluating the combination of everolimus, lapatinib and capecitabine for the treatment of patients with HER2-positive metastatic breast cancer with progression in the CNS after trastuzumab (TRIO-US B-09)

Abstract Background: Improving outcomes for patients with HER2+ CNS metastases remains an unmet clinical need. Lapatinib (L) plus capecitabine (C) yields a 20% objective response rate (ORR) in the CNS in patients with previously treated HER2+ breast cancer brain metastases (Lin N, Clin Cancer Res 2009). Everolimus (E), an oral inhibitor of the mammalian target of rapamycin (mTOR), penetrates into the CNS in murine xenograft models (Meikle L, J Neurosci 2008). TRIO-US B09 is an investigator-initiated trial evaluating the safety and clinical activity of the novel combination of L+C+E for the treatment of patients with HER2+ breast cancer brain metastases. Methods: Patients with trastuzumab-pretreated, HER2+ metastatic breast cancer (MBC) with progression of disease (PD) in the brain and a measurable brain lesion participated. Patients were excluded if they had a prior mTOR inhibitor or an ECOG PS&amp;gt;2. Prior L and/or C, and prior surgery and/or radiation to the brain were allowed. The primary endpoint was CNS ORR at 12 weeks (cycle 3) by RECIST 1.1. Secondary endpoints included safety, progression-free survival, overall survival and extra-CNS ORR. To test the safety of the combination of L+C+E, a 3+3 dose escalation phase was conducted (starting doses: L 1000 mg QD, E 5 mg QD, C: 750 mg/m2 BID d1-14). Treatment was given Q21 days. Patients were evaluated for dose limiting toxicities during C1. Tumor imaging was conducted every 3 cycles. MRI of the brain was performed every 2 cycles through cycle 6 and then every 3 cycles. Neurological symptom assessment was conducted on day 1 of every cycle. Study participants continued to receive treatment until PD, unacceptable toxicity or withdrawal of consent for 12 mos. Results: Nineteen patients were enrolled at 11 sites in the US and treated with at least one dose of study drug. Of 18 patients with data available, median age was 58.5 (45-68), median number of systemic therapies for MBC was 2 (0-6), and 94.4% had prior radiation and/or surgical resection of brain metastases. 10 patients participated in the dose escalation phase of the study. The maximum tolerated doses were determined to be L 1000 mg QD, E 10 mg QD + C 1000 mg/m2BID days 1-14; however, given tolerability concerns, dose expansion proceeded with Cohort 2 dose for C (750 mg/m2 BID d1-14). Of 17 eligible patients with imaging results available to date, 2 (12%) had a partial response in the CNS at week 12, one of whom continues on study (currently in cycle 13). Stable disease was observed in 7 patients. The most common grade 3/4 adverse events (AE) (CTCAE v4.0) related to E and/or L in 18 treated patients were anorexia (5.5%), dehydration (5.5%), diarrhea (17%), fatigue (5.5%), fever (5.5%) hyperglycemia (5.5%), hypokalemia (11%), and oral mucositis (17%). Conclusions: This is the first report of this regimen for patients with HER2+ MBC to the brain. This regimen is generally well-tolerated and shows promising activity in the CNS of heavily pretreated patients. Final efficacy and toxicity analyses for all 19 patients will be presented. Citation Format: Hurvitz SA, Martinez DA, Singh R, Taguchi J, Chan D, Dichmann R, Castrellon A, Barstis J, Hu E, Berkowitz J, Mani A, DiCarlo B, Smalberg I, Hobbs E, Slamon DJ. Phase Ib/II single-arm trial evaluating the combination of everolimus, lapatinib and capecitabine for the treatment of patients with HER2-positive metastatic breast cancer with progression in the CNS after trastuzumab (TRIO-US B-09) [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 P1-12-07.

Treatments and Outcomes of Patients with Multiple Myeloma (MM) Older Than 75 Years of Age: A Single Institution Experience

AbstractAbstract 4756 Background:Considerable advances in the treatment of myeloma patients have culminated in the approval of novel agents (thalidomide, bortezomib, lenalidomide) with survival benefits noted for each. The outcomes of patients younger than 65 years have been shown to be improved with the availability of novel therapies. However, older adults, who comprise the majority of patients with myeloma, have not experienced the same improvement in outcomes as noted in epidemiologic studies (Brenner et al. Hematologica 2009. 94(2): 270 and Schaapveld et al, Eur J Cancer. 2009. 46(1):160.). We postulated that lack of access to novel agents, difference in disease biology, or competing causes of mortality might explain this finding. Method:We conducted a retrospective review of electronic medical records for patients 75 years of age or older at the time of diagnosis with symptomatic myeloma after 2004 (to allow for the availability of novel agents). Demographic information including comorbid conditions, disease characteristics (including risk features and cytogenetics), treatment information as well as survival data was collected. Risk stratification (standard or high risk) was based on the Mayo criteria (Steward et al. Leukemia 2007; 21: 529). Result:72 patients (median age 78 years, range 75–89, 58% were older than 80 years) with symptomatic myeloma were the subjects of this study. Seventy-two percent were males and 28%, 15%, 60% and 29% had a history of cardiac dysfunction (defined as CAD or CHF), diabetes, hypertension and another malignancy (excluding non melanoma skin cancer) respectively. While 31 patients had missing information to determine the International Staging System; 29%, 32% and 39% had ISS stages 1, 2, and 3, respectively (similar to what is expected in younger cohorts). Moreover, using the Mayo risk model, 31% of patients had high risk disease. The median number of systemic therapies received was 2 (range 0–6). First line therapy did not include a novel agent in 29% of patients (who received alkylating agents 12%, anthracyclines 4%, corticosteroids alone 13%) and at the time of relapse, all but 4 patients had received a novel agent. First line therapy consisted of lenalidomide based regimens (30%), bortezomib based regimens (12%), thalidomide based regimens (28%) and a combination of novel agents (1%). The median overall survival for the entire cohort was 46 months (95% CI: 36.4–56.2 months). Conclusion:Older adults (greater than 75 years of age) with multiple myeloma continue to experience a shortened survival despite the use of novel agents and without a discernable higher incidence of high risk disease suggesting competing causes of mortality and tolerance to therapy may significantly limit the benefit of novel therapies in this age group. To address these limitations, we have initiated a clinical trial evaluating a sequential response adapted lenalidomide based therapy for older adults with newly diagnosed myeloma in order to minimize treatment related toxicities. Disclosures:Alsina:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Ortho Biotech: Research Funding. Baz:celgene: Consultancy, Research Funding; millenium: Research Funding; orthobiotec: Research Funding.