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PURPOSE CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1–specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti–programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma. PATIENTS AND METHODS Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed. RESULTS A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1–specific T cells ( P = .01) and NY-ESO-1–specific antibody responses ( P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02). CONCLUSION Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti–programmed death ligand-1 therapies merits further evaluation in other clinical contexts.

Purpose:LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1–expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors.Patients and Methods:Adults with previously treated, advanced, NY-ESO-1–positive solid tumors and limited tumor burden were eligible. LV305 was administered every 3 weeks by intradermal injection in four dose cohorts (Cohort 1: 108 vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 108 vg, 109 vg, 1010 vg x 4 doses).Results:Thirty-nine patients were enrolled: 3 patients each in Cohorts 1, 1A, and 2, and 30 patients in Cohort 3. No dose-limiting toxicities were observed. Tumor types included sarcoma (n = 24), ovarian (n = 8), melanoma (n = 6), and lung cancer (n = 1). All treatment-related adverse events were grade 1 or 2. Common treatment-related adverse events were fatigue (49%), injection site reactions (46%), and myalgia (21%). The disease control rate was 56.4% in all patients and 62.5% in sarcoma patients. One patient with synovial sarcoma achieved a partial response lasting >36 months. Anti–NY-ESO-1-specific CD4+ and/or CD8+ T cells were induced in 57% of evaluable sarcoma patients. Induction of an anti–NY-ESO-1 immune response was associated with improved 1-year survival in an exploratory analysis.Conclusions:This first-in-class, first-in-human study of LV305 demonstrated a favorable safety profile, induction of antigen-specific responses, and potential clinical activity in patients with advanced cancer.

Figure S1 shows Kaplan-Meier curves for progression-free and overall survival in patients with sarcoma.

Table S1 shows maximum eligible tumor burden by tumor type.

Background Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials. Methods In this multi‐center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first‐line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression‐free survival (PFS) were evaluated using the Kaplan‐Meier method and Cox regression. Results At start of first‐line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first‐line therapy for SS was 24.7 months (95% CI, 20.9‐29.4) and 7.5 months, respectively (95% CI, 6.4‐8.4). Median OS and median PFS from start of first‐line therapy for MRCL was 29.9 months (95% CI, 27‐44.6) and 8.9 months (95% CI 4.5‐12.0). Conclusions To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real‐world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature., This comprehensive analysis of real‐world outcomes in patients with advanced synovial sarcoma and myxoid round cell liposarcoma provides greater insight into clinical outcomes than previously published research. These data have the potential to inform prognosis and treatment decisions, as well as provide guidance in the development of future clinical trials.

Introduction: Prostate cancer is the second most common cancer among men worldwide. In 2021, it is estimated that 248,530 men in the United States will be diagnosed with prostate cancer, and 34,130 will die from the disease. Although current treatments have success initially, development of resistance commonly leads to recurrence of an incurable castrate-resistant form of the disease. Thus, significant need for novel therapies to improve the outcome of castrate-resistant prostate cancer remains. B7-H3 (CD276), a member of the B7 family of immunomodulatory molecules, is overexpressed in primary and metastatic prostate cancer, and correlates with disease severity and poor clinical outcome. MGC018, a duocarmycin-based B7-H3 antibody-drug conjugate, is currently being evaluated in clinical studies. Here, MGC018 was explored preclinically to assess the potential for targeting B7-H3 in prostate cancer. Methods: Immunohistochemistry studies were performed to define the expression of B7-H3 in prostate cancer tissue microarrays (TMA). In vivo efficacy studies were conducted with human prostate cancer cell line-derived xenograft (CDX) models to explore the antitumor activity of MGC018 as a single agent and in combination with Poly (ADP-ribose) polymerase (PARP) and androgen receptor (AR) inhibitors. Based on the results in the CDX studies, in vivo efficacy studies were extended to a panel of metastatic prostate cancer patient-derived xenograft (PDX) models, which exhibit heterogenous expression of B7-H3 and more closely mimic the biological characteristics of patient tumors. Results: Staining of prostate tumor TMAs revealed high expression of B7-H3 in primary and metastatic prostate cancer. Of the prostate samples evaluated, 95% (38/40) of the tumor samples were positive for B7-H3 (H-score ≥ 20): 65% had H-scores greater than 200, while 20% and 10% had H-scores between 101-200 and 1-100, respectively. MGC018 demonstrated in vitro cytotoxicity toward B7-H3-positive human prostate cancer cell lines. The in vitro cytotoxicity translated to potent antitumor activity in vivo toward prostate cancer CDX models, and the antitumor activity of MGC018 was enhanced when combined with inhibitors of PARP or AR. In PDX models of metastatic prostate cancer, MGC018 was active as a single agent toward heterogeneous B7-H3-expressing tumors, and combining MGC018 with inhibitors of PARP or AR led to a greater response in some models. Conclusion: B7-H3 is frequently overexpressed in prostate cancer. MGC018 demonstrated potent antitumor activity in vivo toward CDX and PDX models of prostate cancer, and enhanced antitumor activity when combined with inhibitors of PARP or AR. These results support prostate cancer as an indication that may be responsive to ADC-based treatments directed toward B7-H3. MGC018 is being investigated in metastatic prostate cancer in a Phase 1/2 clinical study. Citation Format: Juniper A. Scribner, Francine Z. Chen, Anushka De Costa, Ying Li, Michael Chiechi, Thomas Son, Jeff Hooley, Jonathan Li, Scott Koenig, Chet Bohac, Ezio Bonvini, Paul A. Moore, Deryk Loo. Targeting B7-H3 in prostate cancer: Preclinical proof of concept with MGC018, an investigational anti-B7-H3 antibody-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 330.

Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.

Purpose The decision to prescribe packed red blood cell (PRBC) transfusions in patients with chemotherapy-induced anemia (CIA) includes assessment of clinical features such as the patient’s cancer type and treatment regimen, severity of anemia symptoms, and presence of comorbidities. We examined contemporary transfusion practices in patients with nonmyeloid cancer and CIA. Methods Key inclusion criteria were age ≥ 18 years with nonmyeloid cancer, receiving first/second-line myelosuppressive chemotherapy, baseline hemoglobin (Hb) ≤ 10.0 g/dL, and planned to receive ≥ 1 PRBC transfusions. Exclusion criteria were receipt of erythropoiesis-stimulating agents within 8 weeks of screening and/or chronic renal insufficiency. Data were collected from patients’ medical records, laboratory values, and physician/provider questionnaires. Proportion of patients for each clinical consideration leading to a decision to prescribe a PRBC transfusion and 95% exact binomial confidence intervals were determined. Results The study enrolled 154 patients at 18 sites in USA; 147 (95.5%) received a PRBC transfusion. Fatigue was the most common symptom affecting the decision to prescribe a PRBC transfusion (101 [69.2%] patients). Of the three reasons selected as primary considerations for prescribing a PRBC transfusion, anemia symptoms (106 [72.1%] patients) was the most frequently reported, followed by Hb value (37 [25.2%] patients) and medical history (4 [2.7%] patients). Conclusions In this study, the primary consideration for prescribing a PRBC transfusion was anemia symptoms in 72.1% of patients, with only 25.2% of patients prescribed a transfusion based exclusively on Hb value. Results indicate that clinical judgment and patient symptoms, not just Hb value, were used in decisions to prescribe PRBC transfusions. Electronic supplementary material The online version of this article (10.1007/s00520-017-4035-7) contains supplementary material, which is available to authorized users.

Preclinical data suggest that a “prime-boost” vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broad anti-NY-ESO-1 immune response. It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein. This multicenter phase 1b, first-in-human trial evaluated CMB305 in patients with NY-ESO-1 expressing solid tumors. Safety was examined in a 3 + 3 dose-escalation design, followed by an expansion with CMB305 alone or in a combination with either oral metronomic cyclophosphamide or intratumoral injections of a toll-like receptor agonist (glucopyranosyl lipid A). Of the 79 patients who enrolled, 81.0% had sarcomas, 86.1% had metastatic disease, and 57.0% had progressive disease at study entry. The most common adverse events were fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%). In patients with soft tissue sarcomas, a disease control rate of 61.9% and an overall survival of 26.2 months (95% CI, 22.1–NA) were observed. CMB305 induced anti-NY-ESO-1 antibody and T-cell responses in 62.9% and 47.4% of patients, respectively. This is the first trial to test a prime-boost vaccine regimen in patients with advanced cancer. This approach is feasible, can be delivered safely, and with evidence of immune response as well as suggestion of clinical benefit.

INTRODUCTION: Anemia is a common adverse effect of myelosuppressive chemotherapy, and the development of chemotherapy-induced anemia (CIA) is more common in patients with hematologic malignant tumors. OBJECTIVE: To assess the incidence and treatment pattern of CIA in patients diagnosed with non-Hodgkin lymphoma (NHL) from a large managed care organization in California. METHODS: Patients diagnosed with NHL between 2010 and 2012 were studied to provide an updated picture of CIA in current hematology-oncology practice. Trends in anemia treatment patterns were examined from 2000 to 2013. All data were collected from Kaiser Permanente Southern California electronic health records. RESULTS: Of 699 chemotherapy-treated patients with NHL diagnosed between 2010 and 2012, 36.9% and 11.6% developed moderate (hemoglobin < 10 g/dL) and severe (hemoglobin < 8 g/dL) CIA during chemotherapy, respectively. Proportions of moderate CIA events treated with erythropoiesis-stimulating agents (ESAs) decreased from 2000 to 2013: 34% in phase 1 (January 1, 2000, to December 31, 2006), 22% in phase 2 (January 1, 2007, to March 24, 2010), and 6% in phase 3 (March 25, 2010, to June 30, 2013). An increasing trend of red blood cell transfusion was observed: 12% in phase 1, 22% in phase 2, and 27% in phase 3. Similar calendar trends were observed for management of severe CIA events. DISCUSSION: In contrast to previous European reports, we note a higher incidence of CIA in patients with NHL in this US community practice setting. CONCLUSION: Moderate to severe CIA is common in patients with NHL receiving chemotherapy. Multiple ESA-related policy changes occurred from 2000 to 2013. A large proportion of CIA episodes were currently not treated with ESA, and transfusions have become more common. Further studies are needed to determine associations between CIA symptom burden and CIA treatment as they relate to patient outcomes and quality of life.

Introduction: Squamous cell carcinoma of the head and neck (SCCHN) is the seventh most common cancer worldwide, accounting for ~ 4% of all cancers in the United States. Although PD-1-directed therapy has efficacy in SCCHN, 85-95% of patients progress following initial response. B7-H3 is a member of the B7 family of immunomodulatory molecules, is overexpressed in SCCHN, and correlates with disease severity and poor clinical outcome. Furthermore, consistent with its putative coinhibitory function, B7-H3 expression in SCCHN is inversely correlated with the number of tumor infiltrating CD8+ T-cells. We are developing therapeutics targeting B7-H3, including enoblituzumab, an Fc-engineered anti-B7-H3 monoclonal antibody, and MGC018, a duocarmycin-based B7-H3 ADC, both of which are currently being evaluated in clinical studies. Here the potential of MGC018 was explored in preclinical models as a proof of concept for targeting B7-H3 in SCCHN. Methods: Immunohistochemistry studies were performed to define the expression of B7-H3 in SCCHN tissue microarrays (TMA). Single and repeat-dose in vivo efficacy studies were conducted in CD-1 nude mice with cell line-derived SCCHN human tumor xenografts to explore the relationship between Cmax, exposure and antitumor activity, and to define the minimal efficacious dose in these models. Based on results in these cell-derived xenograft (CDX) studies, in vivo efficacy studies were extended to a panel of SCCHN patient-derived xenograft (PDX) models, which more closely mimic the biological characteristics of the patient tumor and exhibit heterogenous expression of B7-H3. Results: Analysis of B7-H3 expression on a SCCHN TMA confirmed and extended previously reported expression of B7-H3 in SCCHN. Of the SCCHN samples evaluated, 90% (36/40) of the tumor samples were positive for B7-H3: 35% (14/40) had H-scores greater than 200, with the remaining 22 samples equally distributed between the H-score range of 101-200 and 1-100 (~ 28% each). MGC018 demonstrated specific, dose-dependent in vitro cytotoxicity toward SCCHN human tumor cell lines. The in vitro cytotoxicity translated to potent antitumor activity in vivo against SCCHN CDX models, with a single administration of 3 mg/kg resulting in complete responses in 7/7 mice in the FaDu model. In the PDX setting (H-scores 120-283), repeat dose administration every week or two weeks with MGC018 at 3 mg/kg/dose, led to regressions and/or stable disease in 10/18 models, and a delay in tumor growth in 5 additional models. Conclusion: B7-H3 is frequently overexpressed in SCCHN. At clinically relevant dose levels, MGC018 demonstrated potent antitumor activity in vivo toward SCCHN CDX mouse models and the majority of SCCHN PDX mouse models examined. These results support SCCHN as a potential indication that may be responsive to ADC-based treatments directed toward B7-H3. Citation Format: Juniper A. Scribner, Francine Z. Chen, Ying Li, Michael Chiechi, Thomas Son, Jeff Hooley, Scott Koenig, Paul A. Moore, Ezio Bonvini, Chet Bohac, Deryk Loo. Targeting B7-H3 in squamous cell carcinoma of the head and neck: Preclinical proof-of-concept with the investigational anti-B7-H3 antibody-drug conjugate, MGC018 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 950.

To evaluate moderate (grade 2, hemoglobin10 g/dl) and severe (grade 3+, hemoglobin8 g/dl) anemia as potential risk factors for DDR in the first line course of chemotherapy. While chemotherapy-induced neutropenia has been shown to be associated with dose delay/reduction (DDR) in several studies, the effect of anemia is less well studied.We identified 3955 Kaiser Permanente patients diagnosed with incident non-Hodgkin's lymphoma (n = 574), breast (n = 2043), lung (n = 463), gastric (n = 113), ovarian (n = 204), or colorectal cancers (n = 558) between 2010 and 2012. Generalized linear mixed effects models were used to study the effect of anemia in subsequent cycles, adjusting for demographics, comorbidities, chemotherapy cycle, neutropenia, thrombocytopenia, and liver and renal function.We found that moderate (grade 2) to severe (grade 3-4) anemia increased the risk of DDR in subsequent chemotherapy cycles [odds ratio (OR) = 1.46, 95 % CI (1.32, 1.62) and OR = 2.02 (1.41, 2.89)], respectively, compared to grade 1 or no anemia. Both stage I-III and IV patients with grade 2 or greater anemia were at higher risk for DDR than patients with grade 1 or no anemia [ORstage IV, grade 2 = 1.94 (1.58, 2.38); ORstage IV, grade 3/4 = 2.83 (1.42, 5.62) and ORstage I-III, grade 2 = 1.33 (1.18, 1.49); ORstage I-III, grade 3-4 = 1.81 (1.18, 2.76)].These results provide insight into novel risk factors for chemotherapy dose modification that may inform clinicians on management strategies to optimize treatment outcomes.

Purpose In 1997, Vogelzang et al. reported that 61 % of patients with cancer indicated fatigue impacted daily life more than pain, and only 37 % of oncologists shared this perception. We provide an update to this study, which can help prioritize symptom assessment and management in the clinic. Study aims were to determine and compare perceptions of patients with cancer and health care providers (HCPs) of the impact of fatigue and pain. Methods A random sample of patients with cancer was recruited in the USA by Harris Poll Online and Schlesinger Associates. Oncology HCPs were recruited by Food and Drug Research, Inc. and Toluna, Inc. Results From June to November 2012, 550 of 1122 eligible patients (49 %), 400 of 533 eligible oncologists (75 %), and 400 of 617 eligible oncology nurses (65 %) completed a survey. Of patients, 58 % reported that fatigue affected their daily lives more than pain while undergoing treatment with chemotherapy versus 29 % of oncologists and 25 % of oncology nurses that had this perception. Ninety-eight percent of patients reported experiencing fatigue, whereas 72 % of oncologists and 84 % of oncology nurses thought this was the case. Eighty-six percent of patients reported pain while undergoing treatment with chemotherapy, whereas 36 % of oncologists and 51 % of oncology nurses believed this occurred. Nausea and vomiting felt by HCPs were the most concerning symptoms for patients (88 %). Conclusions This study shows the importance of assessing symptoms by direct patient report during chemotherapy treatment. HCPs continue to underestimate the prevalence and importance of fatigue and pain for patients with cancer, a finding that may alter the management of treatment-related symptoms and may influence the development of patient symptom management plans. Electronic supplementary material The online version of this article (doi:10.1007/s00520-016-3275-2) contains supplementary material, which is available to authorized users.

Introduction: B7-H3, a member of the B7 family of immunomodulatory molecules, is overexpressed in a wide range of solid tumors. B7-H3 tumor overexpression has been correlated with disease severity and poor outcome. MGC018 is a duocarmycin-based antibody-drug conjugate (ADC) targeting B7-H3. MGC018 exhibits a favorable preclinical profile, with strong reactivity toward tumor cells and tumor-associated vasculature, limited normal tissue reactivity, and potent antitumor activity toward B7-H3-expressing tumor xenografts. With the emergence of immune-checkpoint blockade as a promising treatment for cancer, interest has grown in understanding the potential of cytotoxic agents to promote immune surveillance or stimulate immune responses to dying cancer cells, leading to immunological memory. ADCs bearing tubulin and DNA modifying cytotoxic payloads have been reported to induce immunological cell death (ICD), mediate antitumor immunity in immunocompetent mouse models, and synergistically combine with checkpoint inhibitors to deliver enhanced antitumor responses. Based on those results, we investigated the immunomodulatory potential of MGC018 and the prospect to combine with checkpoint blockade to enhance antitumor responses. Methods: Syngeneic mouse models expressing human B7-H3 were employed to investigate the antitumor activity of MGC018 in an immune competent setting. Studies were conducted to assess the role of the immune system in the MGC018-mediated antitumor responses, whether MGC018 could impart antitumor memory responses in vivo, and the potential to enhance antitumor responses by combining MGC018 with PD-1 blockade. Results: MGC018 demonstrated specific, dose-dependent in vivo antitumor activity toward human B7-H3-bearing tumors in immunocompetent syngeneic mouse models. Depletion of CD8+ T cells led to reduced antitumor responses, indicating that CD8+ T cells contributed to MGC018-mediated antitumor activity. Antitumor activity in these models was enhanced when MGC018 was combined with anti-PD-1. Treatment with MGC018 alone, or in combination with anti-PD-1, led to complete antitumor responses, and the majority of mice rejected subsequent tumor rechallenge. Conclusion: MGC018, a clinical-stage therapeutic comprised of a humanized antibody targeting B7-H3, conjugated to a duocarmycin-based DNA alkylating payload, exhibits a favorable preclinical profile. Results from these syngeneic model studies support the hypothesis that the antitumor activity of the duocarmycin-based MGC018 ADC (1) mediates immunomodulatory activity, (2) is enhanced by combination with checkpoint blockade, and (3) induces immunological memory. Our findings support a clinical strategy that combines MGC018 with checkpoint blockade for the treatment of B7-H3-expressing solid cancers. Citation Format: Juniper A. Scribner, Michael Chiechi, Pam Li, Thomas Son, Jeff Hooley, Ying Li, Anushka De Costa, Peter Lung, Nicholas Yee-Toy, Francine Chen, Bhaswati Barat, Christina Wolff, Valentina Ciccarone, James Tamura, Scott Koenig, Chet Bohac, Jon Wigginton, Paul A. Moore, Ezio Bonvini, Deryk Loo. MGC018, a duocarmycin-based antibody-drug conjugate targeting B7-H3, exhibits immunomodulatory activity and enhanced antitumor activity in combination with checkpoint inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5203.

Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.

Background: Fatigue associated with chemotherapy-induced anemia (CIA) is common in patients with breast cancer, and can have adverse effects on quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) reduce the need for transfusions and may improve QoL in patients with symptomatic CIA. Information on hemoglobin (Hb) levels and effects of fatigue on QoL in patients with breast cancer and CIA in real-world clinical practice is limited. Methods: The Electronic Assessment of Quality of Life in Patients With Symptomatic CIA (eAQUA) study evaluated improvements in QoL for patients with CIA receiving ESAs who had an increase in Hb of ≥1 g/dL by week 9. This phase 4, international, longitudinal, prospective, observational study enrolled patients with solid tumors who received chemotherapy and had symptomatic anemia. Patients received ESA therapy for up to 13 weeks based on European indication. The primary outcome was the proportion of patients with increase in Hb ≥1 g/dL and improvement in fatigue-related QoL based on the Functional Assessment of Cancer Therapy-Fatigue (FACT-F; scale = 0 to 52 with lower scores indicating worse fatigue) subscale scores and fatigue Visual Analog Scale (VAS; scale = 0 to 100 with higher scores indicating worse fatigue) from baseline to week 9. FACT-F change scores were anchored to VAS change scores to determine the minimally important difference (MID) for improvements in QoL. Patients with a FACT-F change score that was ≥ the MID were considered to have an improvement in QoL. For Hb and QoL outcomes, week 9 data were those assessed closest to on-treatment day 57 (after initiation of ESA) and within on-treatment days 43 to 70 inclusive, to account for different ESA dosing schedules and the observational nature of the study. Secondary outcomes included rates of red blood cell (RBC) transfusions or iron supplementation during the study. Results: Of 1262 patients enrolled in eAQUA, 289 had breast cancer and were included in the full analysis set (FAS; had at least one ESA dose); of these, 152 patients were eligible to be included in the primary analysis set (PAS; had QoL and Hb data available at baseline and week 9). At baseline, mean (standard deviation [SD]) Hb was 9.4 (0.6) g/dL; mean (SD) FACT-F and VAS scores were 27.1 (10.5) and 52.7 (22.8), respectively, in the FAS. Mean (SD) change from baseline at week 9 was 1.3 (1.3) g/dL for Hb; 4.1 (10.8) score change for FACT-F; and 4.7 (25.9) score change for VAS in the FAS. A total of 54 (18.7%) patients in the FAS required an RBC transfusion and 79 (27.3%) received iron supplementation. At week 9, 77 of 152 patients in the PAS had achieved improvement in fatigue-related QoL (50.7%; 95% confidence interval [CI] = 42.7%, 58.6%); 93 patients had increased Hb ≥1 g/dL (61.2%; 95% CI = 53.4%, 68.9%); and 59 patients (38.8%; 95% CI = 31.1%, 46.6%) had achieved both improvement in fatigue-related QoL and increased Hb ≥1 g/dL. Conclusions: In this exploratory subgroup analysis, patients with breast cancer and symptomatic CIA treated with ESAs achieved clinically meaningful improvements in fatigue-related QoL and Hb levels. Citation Format: Mario Airoldi, Dominique Spaeth, Joan Van den Bosch, Charalambos Christofyllakis, Laura Belton, Chet Bohac, Jan-Henrik Terwey, Giuseppe Tonini. Hemoglobin levels and quality of life in patients with breast cancer and symptomatic chemotherapy-induced anemia enrolled in the eAQUA study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-18.

A meta-analysis of trials of ESA use in patients with breast cancer receiving chemotherapy was conducted. Nine studies were analyzed (ESAn = 2346; controln = 2367). The overall stratified random-effects odds ratio (95% CI) was 1.17 (0.99–1.39) for death and 1.01 (0.87–1.16) for disease progression-related end points. Odds ratios remain consistent with prior data after including recent results. Background New data on erythropoiesis-stimulating agents (ESAs) regarding overall survival and disease progression-related outcomes in patients with breast cancer receiving chemotherapy are presented in a meta-analysis of controlled trials of ESA use (epoetin a, epoetin b, darbepoetin a, biosimilars). Patients and methods A literature search identified reports from January 1997 through March 2014. We used company databases for Amgen, Inc., or Janssen studies and published data for other studies. Random-effects odds ratios (ORs) were calculated to compare results for patients randomized to ESA with those randomized to control. Results Deaths were reported for 571 of 2346 patients (24%) in the ESA groups and 523 of 2367 patients (22%) in the control groups [OR, 1.20; 95% confidence interval (CI) 1.03–1.40]. Sensitivity analyses were conducted to explore the effects of individual studies and exclusion of one study (BEST) resulted in an OR for death of 1.12 (95% CI 0.94–1.34). In seven studies reporting progression-related end points (N = 4197; ESAn = 2088; controln = 2109), the OR was 1.01 (95% CI 0.87–1.16) for ESA compared with control. Conclusions After incorporating recent results of ESA use in patients with breast cancer, risks of survival and progression-free survival remain consistent with previously published data.

Data on efficacy and safety of darbepoetin alfa (DA) administered at hemoglobin (Hb) ≤10 g/dL are limited. In this analysis, we examined DA's efficacy and safety in patients with Stage IV cancers and chemotherapy‐induced anemia (CIA) initiated on DA at Hb ≤10 g/dL. Data for patients with Stage IV cancers and CIA and who initiated DA at Hb ≤10 g/dL were extracted from three phase 3 trials identified in a central database of Amgen‐sponsored DA studies in CIA. Efficacy outcomes were assessed by achievement of Hb increases of ≥1 g/dL and ≥2 g/dL and red blood cell (RBC) or whole blood transfusion requirements. Data were analyzed for all patients with baseline Hb ≤10 g/dL, and by the subgroups of patients with baseline Hb ≥9 to ≤10 g/dL versus

Erythropoiesis-stimulating agents (ESAs) are approved to treat anemia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. ESAs reduce transfusion rates, but some clinical studies suggest that ESAs may reduce survival or increase disease progression. This study-level meta-analysis examined the effects of darbepoetin alfa, epoetin alfa or epoetin beta on mortality, disease progression and transfusion incidence in patients with lymphoproliferative malignancies, using randomized, controlled trials of patients receiving chemotherapy and ESAs or standard of care. The odds ratio (OR) for mortality was 1.04 (95% confidence interval [CI], 0.81–1.34, random-effects model, 10 studies); the risk difference was − 0.01 (95% CI, − 0.03–0.02). The OR for disease progression was 1.02 (95% CI 0.81–1.30, random-effects model, five studies). A lower proportion of ESA-treated patients than controls received transfusions (seven studies). In this meta-analysis, ESAs reduced transfusions with no clear effect on mortality or disease progression in patients with lymphoproliferative malignancies receiving chemotherapy.

Jean-Loup Mouysset,1 Beata Freier,2 Joan van den Bosch,3 Charles Briac Levaché,4 Alain Bols,5 Hans Werner Tessen,6 Laura Belton,7 G Chet Bohac,8 Jan-Henrik Terwey,9 Giuseppe Tonini101Department of Medical Oncology, Clinique Rambot Provencale, Aix en Provence, France; 2Clinical Oncology, Wojewodzki Szpital Specjalistyczny, Wroclaw, Poland; 3Department of Internal Medicine/Oncology, Albert Schweitzer Ziekenhuis locatie Dordwijk, Dordrecht, the Netherlands; 4Radiotherapy Service, Medical Oncology, Polyclinique Francheville, Périgueux, France; 5Central Pharmacy, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium; 6Private Oncology Practice. Goslar, Germany; 7LB Biostatistics, London, UK; 8Clinical Research, Amgen Inc., Thousand Oaks, CA, USA; 9Medical Development – Oncology, Amgen (Europe) GmbH, Zug, Switzerland; 10Department of Medical Oncology, Università Campus Bio-Medico, Roma, ItalyPurpose: To assess hemoglobin (Hb) outcomes and fatigue-related quality-of-life (QoL) (electronic assessment) in patients with solid tumors and symptomatic chemotherapy-induced anemia receiving cytotoxic chemotherapy and darbepoetin alfa (DA) or another erythropoiesis-stimulating agent according to European indication.Methods: eAQUA was a Phase IV prospective observational study. The primary outcome (assessed in the primary analysis set [PAS]: patients receiving one or more DA dose who had baseline and week 9 assessments for Hb and QoL) was the proportion of patients receiving DA having both Hb increases ≥1 g/dL and improved QoL between baseline and week 9. Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale scores were anchored to fatigue visual analog scale scores to determine the minimally important difference for improved QoL. Overall data/data over time are reported for the full analysis set (patients receiving one or more erythropoiesis-stimulating agent dose, n=1,158); week 9 data (ie, data relating to the primary and secondary outcomes) are reported for the PAS (n=510). Baseline and safety data are included for both the full analysis set and PAS.Results: In the PAS, 69% of patients had stage IV disease and 96% were fatigued. The minimally important difference in FACT-F change score for QoL improvement was 3.5. From baseline to week 9, 32% (95% confidence interval: 28%–36%) of patients had both improved QoL and an Hb increase ≥1 g/dL; proportions were similar across the most common tumor types. At week 9, 49% and 58% of patients had improved QoL or Hb increases ≥1 g/dL, respectively; 70% and 76% had QoL or Hb improvements between baseline and study end, respectively. In the PAS, 16% of patients required transfusions and 32% required iron supplementation. Few patients (

of study participants was 75.61 years. Mesothelioma (20%), breast (12%), colorectal (12%), lung (10%), prostate (9%) and melanoma (6%) were the main tumours. Twenty -eight percent of patients were frail using the VES-13 while 34% were frail on the MGA. An impaired VES-13 predicted impairment in the SAS, ECOG, ADL’s, IADL’s, GUGT, GDS, MNASF, MNA, and geriatric syndromes. On ROC curve analysis, the VES-13 predicted impairment on the MGA with an AUC of 0.747. This improved to 0.848 when the MNA short form was added to the model. The VES-13 cut off ≤3 in this group gave a sensitivity to 55.6% and specificity of 87.9% for predicting impairment on the MGA while a cut-off to ≥ 2 increased the sensitivity to 67.7% while dropping the specificity to 82.7%. Increasing the cut-off to 4 increased the specificity to 94.8 at the expense of sensitivity. Conclusion: This study demonstrates that a two stage geriatric screening programme is feasible. It also suggests that in this population using the locally available MGA/CGA items, a lower cut off of 2 maybe better at identifying the patients most likely to be frail for targeted interventions.

Background: Anemia is a common complication of chemotherapy that can cause clinically important symptoms and reduced quality of life. It is unclear how management of chemotherapy induced anemia (CIA) has evolved over time given the changes in the US prescribing information, reimbursement, and implementation of a risk evaluation and mitigation strategy (REMS) for the use of erythropoiesis-stimulating agents (ESAs). Objective: To describe treatment trends and current treatment patterns for anemia during chemotherapy in 2000 to 2013. Methods: Patients diagnosed with incident breast, lung, colorectal, ovarian or gastric cancer who developed moderate to severe anemia (i.e., grade II-IV based on the CTCAE grading system, or hemoglobin Results: A total of 7,266 patients were included in this study (3,374 breast, 1,751 lung, 1,406 colorectal, 503 ovarian and 232 gastric cancer). Overall, 16% of the patients were diagnosed at stage I, 31% at stage II, 30% at stage III and 23% at stage IV. The mean age at diagnosis was 60 years. The observed grade II-IV anemia episodes were 1741 (7,159 pts) in P1, 880 (3,285 pts) in P2, and 1011 (3699 pts) in P3. Figures 1 and 2 show the proportion of various CIA treatment modalities by CIA severity. Proportion of anemia episodes with ESA use decreased from 2006 to 2013 (P1: 28%; P2: 21%; and P3: 3%). An increased trend of transfusion use was observed (P1: 8%; P2: 14%; and P3: 16%), with the greatest increase observed in grade III CIA (P1: 21%; P2: 41%; and P3: 54%). There was also an increase in the proportion of untreated CIA (P1: 66%; P2: 68%; and P3: 80%). When we examined the level of hemoglobin concentration prior to CIA intervention, there was a slight decrease in the hemoglobin concentrations prior to ESA use across calendar periods [mean (SD): 9.7 (1.1) g/dl in P1; 9.6 (1.1) in P2; 9.1 (1.2) in P3, p Similar trends for CIA treatment modalities across the three calendar periods were observed when we restricted the analyses to stage 4 cancer (Figure 3). Conclusion: The study indicates that along with the decreased utilization of ESA, utilization of RBC transfusion has increased significantly over the calendar periods in patients diagnosed with five solid tumors. Approximately 80% of patients with moderate to severe anemia (Hg < 10g/dL) in patients of these common solid tumors remained untreated in most recent calendar period (March 25, 2010–June 30, 2013). Disclosures Chao: Amgen Inc.: Research Funding. Xu:Amgen Inc.: Research Funding. Sattayapiwat:Amgen Inc.: Research Funding. Page:Amgen Inc.: Employment, stockholder Other. Cannavale:Amgen Inc.: Research Funding. Rodriguez:Amgen Inc.: Research Funding. Bohac:Amgen Inc.: Employment, stockholder Other. Xu:Amgen Inc.: Employment, stockholder Other.

Aim: Erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa (DA) can be used to reduce the need for transfusions and improve QoL in patients (pts) with symptomatic chemotherapy-induced anaemia (CIA). eAQUA was a phase 4, prospective, observational study, assessing Hb outcome and fatigue-related QoL (electronic assessment) in pts with solid tumours who had symptomatic CIA and were receiving an ESA according to approved European indication. Primary data and detailed methodology from the eAQUA study are reported in the accompanying abstract (Tonini et al). Methods: Additional analyses for eAQUA included: median time from baseline to an increase in Hb ≥1 g/dL or a QoL improvement (Kaplan-Meier methodology); proportion of pts with both a QoL improvement and a Hb increase ≥1 g/dL at week (wk) 9, by tumour type, and red blood cell (RBC) transfusion/iron use during the course of the study. QoL was measured in terms of Functional Assessment of Cancer Therapy-Fatigue subscale scores and fatigue Visual Analogue Scale scores. Results: 1262 pts were enrolled; the primary analysis set reported here comprised pts who received DA and had baseline and wk 9 Hb and QoL data (n = 510). Overall, 65% of pts were female, 52% were ≥65 years and 56% had competed 1-3 chemotherapy cycles. By tumour type, the proportions of pts having both a Hb increase ≥1 g/dL and QoL improvement at wk 9 were: breast (n = 152) 39% (95% confidence intervals [CI]: 31-47%); ovarian (n = 79) 38% (95% CI: 27-49%); colorectal (n = 71) 31% (95% CI: 20-42%); NSCLC (n = 70) 29% (95% CI: 18-39%) and prostate (n = 39) 28% (95% CI: 14-42%). Median times to Hb increase ≥1 g/dL or QoL improvement were 37 (95% CI: 30-43) days and 40 (95% CI: 34-43) days, respectively. Overall, 82 pts (16%) required ≥1 RBC transfusion; median Hb in the 7 days prior to transfusion was 8.3 (range: 6-12) g/dL. Overall, 163 pts (32%) required iron supplementation. Conclusions: In our study, many pts treated with DA per current European indication for symptomatic CIA had Hb increases ≥1 g/dL and/or QoL improvements within 6 weeks of starting treatment. QoL/Hb improvements were observed across tumour types. Relatively few pts required transfusions or iron supplementation during the study. Disclosure: G. Tonini: received Research funding from Amgen for eAQUA participation; J. Mouysset, M. Rotarski, M. Airoldi, C. Toganel and C. Christofyllakis: has received research funding from Amgen for eAQUA participation; D. Spaeth: has received research funding from Amgen for eAQUA participation and honoraria for symposia participation from Amgen; L. Belton: is a contractor funded by Amgen; C. Bohac: is an Amgen Inc. employee and stockholder; J. Terwey: is an Amgen (Europe) GmbH employee and stockholder.

Aim: Fatigue is common in pts with CIA and can adversely impact QoL. There are limited data related to improvements in Hb levels and fatigue-related QoL in routine clinical practice. Methods: eAQUA was a phase 4, prospective, observational study assessing Hb outcome and fatigue-related QoL (electronic assessment) in pts with solid tumours receiving chemotherapy who had symptomatic CIA and were receiving an erythropoiesis-stimulating agent according to European indications. The primary aim was to determine the proportion of pts receiving darbepoetin alfa (DA) with a Hb increase ≥1 g/dL and improved QoL between baseline and week (wk) 9. Pts receiving DA who had baseline and wk 9 Hb and QoL data represented the primary analysis set (PAS). QoL was measured in terms of Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale scores and fatigue Visual Analogue Scale (VAS) scores (0=least fatigued). FACT-F change scores were anchored to VAS change scores to determine the minimally important difference (MID) for a perceived QoL improvement, based on a predefined algorithm. Pts who had a FACT-F change score ≥ the calculated MID were deemed to have improved QoL. Results: 1262 pts were enrolled; 510 pts were included in the PAS. At baseline, median age was 65 years, 30% had been diagnosed with breast cancer, 69% had stage IV disease and 96% were experiencing fatigue. At baseline, mean (SD) Hb was 9.4 (0.6) g/dL; mean (SD) FACT-F and VAS scores were 29.2 (10.3) and 49.2 (22.6), respectively. Mean (SD) change from baseline in Hb at wk 9 was 1.2 (1.4) g/dL; mean (SD) change in FACT-F and VAS scores were 3.5 (10.5) and 4.3 (24.7). The mean (SD) FACT-F change determined to be the MID for a QoL improvement was 3.5 (5.5). Overall, 32% (95% CI: 28-36%) of pts met the primary endpoint with both a Hb increase ≥1 g/dL and improved QoL at wk 9. The proportions of pts achieving either improvements in QoL or Hb ≥1 g/dL at wk 9 were 49% and 58%; 70% and 76% of pts had improvements in QoL or Hb levels at any time up to end of study. Conclusions: In our study, pts with solid tumours receiving DA per European indication for symptomatic CIA had a clinically meaningful improvement in both Hb levels and QoL. Disclosure: G. Tonini, J. Mouysset, B. Freier, J. van den Bosch, A. Bols and H.W. Tessen: Research funding from Amgen for eAQUA participation; C.B. Levache: is voluntary President of association called “association pour la recherche clinique de francheville”, which received a payment on behalf of AMGEN to realize the e-aqua study; L. Belton: Contractor funded by Amgen; C. Bohac: Amgen Inc. employee and stockholder; J. Terwey: Amgen (Europe) GmbH employee and stockholder.