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  • 1
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 12 ( 2022-12-01), p. 2991-2998
    Abstract: Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium–glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes. RESULTS Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79–0.96) without SGLT2i and 0.67 (95% CI 0.42–1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69–0.92) without SGLT2i and 0.42 (95% CI 0.16–1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment. CONCLUSIONS Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1490520-6
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  • 2
  • 3
    In: The Oncologist, Oxford University Press (OUP), Vol. 25, No. 8 ( 2020-08-01), p. e1233-e1241
    Abstract: Eflapegrastim, a novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Preclinical and phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for neutrophil counts for eflapegrastim versus pegfilgrastim. This open-label phase III trial compared the efficacy and safety of eflapegrastim with pegfilgrastim for reducing the risk of chemotherapy-induced neutropenia. Materials and Methods Patients with early-stage breast cancer were randomized 1:1 to fixed-dose eflapegrastim 13.2 mg (3.6 mg G-CSF) or standard pegfilgrastim (6 mg G-CSF) following standard docetaxel plus cyclophosphamide chemotherapy for 4 cycles. The primary objective was to demonstrate the noninferiority of eflapegrastim compared with pegfilgrastim in mean duration of severe neutropenia (DSN; grade 4) in cycle 1. Results Eligible patients were randomized 1:1 to study arms (eflapegrastim, n = 196; pegfilgrastim, n = 210). The incidence of cycle 1 severe neutropenia was 16% (n = 31) for eflapegrastim versus 24% (n = 51) for pegfilgrastim, reducing the relative risk by 35% (p = .034). The difference in mean cycle 1 DSN (−0.148 day) met the primary endpoint of noninferiority (p & lt; .0001) and also showed statistical superiority for eflapegrastim (p = .013). Noninferiority was maintained for the duration of treatment (all cycles, p & lt; .0001), and secondary efficacy endpoints and safety results were also comparable for study arms. Conclusion These results demonstrate noninferiority and comparable safety for eflapegrastim at a lower G-CSF dose versus pegfilgrastim. The potential for increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study in patients at higher risk for CIN. Implications for Practice Chemotherapy-induced neutropenia (CIN) remains a significant clinical dilemma for oncology patients who are striving to complete their prescribed chemotherapy regimen. In a randomized, phase III trial comparing eflapegrastim to pegfilgrastim in the prevention of CIN, the efficacy of eflapegrastim was noninferior to pegfilgrastim and had comparable safety. Nevertheless, the risk of CIN remains a great concern for patients undergoing chemotherapy, as the condition frequently results in chemotherapy delays, dose reductions, and treatment discontinuations.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2023829-0
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  • 4
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. Suppl 2 ( 2021-11), p. A470-A470
    Abstract: Eftilagimod alpha (efti) is a soluble LAG-3 protein targeting a subset of MHC class II molecules, effectively mediating antigen presenting cell (APC) and CD8 T-cell activation. Interim data from a phase II trial of efti plus pembrolizumab (TACTI-002) showed encouraging antitumor activity and manageable safety in patients treated for second line metastatic head and neck squamous cell carcinoma (HNSCC). TACTI-003 ( NCT04811027 ) is the multicenter, open label, randomized phase II trial to investigate efti plus pembrolizumab in the first line setting for HNSCC patients. Methods A planned total of 154 patients (pts), unselected for PD-L1 expression, will be recruited into two cohorts (figure 1). In cohort A, CPS≥1 pts will be randomly assigned 1:1 to receive either efti (30 mg subcutaneously Q2W for initial 6 months, thereafter Q3W for up to 2 years) plus pembrolizumab (400 mg intravenously Q6W for up to two years) or pembrolizumab alone. CPS will be stratified (1–19 vs. ≥ 20 and ECOG 0 vs. 1). Cohort B will include pts with CPS 〈 1 who will receive efti plus pembrolizumab without randomization. Imaging will be performed every 9 weeks. The primary end point (EP) is objective response rate (ORR) by RECIST1.1. Secondary EPs include overall survival, ORR according to iRECIST, time to and duration of response, disease control rate, progression free survival, occurrence of anti-efti -specific antibodies, safety, and quality of life. Exploratory endpoints comprise biomarkers. The study has been approved by relevant competent authorities, ethic committees and IRBs. Abstarct 440 Figure 1 Trial design Trial Registration NCT04811027 Ethics Approval The study was approved by relevant ethic committees and institutional review boards.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2719863-7
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 9046-9046
    Abstract: 9046 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 1st line non-small cell lung carcinoma (NSCLC) part of the phase II trial (NCT03625323). Methods: Patients (pts) with untreated, immunotherapy naïve, advanced NSCLC unselected for PD-L1 expression were recruited into part A. The study used a Simon's 2-stage design (17 pts planned for stage 1 and 19 pts for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, PD and immunogenicity. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks locally and with blinded independent central review (BICR) retrospectively. The study was approved by ethic committees and institutional review boards. Results: In total 36 pts were enrolled. At data cut-off (Jan 2021; median FU of 14 months), the median age was 69 yrs (range 53-84) and 69 % were male. The ECOG PS 0 and 1 was 42% and 58% respectively. Patients had squamous (42%) and non-squamous (58%) NSCLC and 95% presented with metastatic disease. All PD-L1 subgroups (TPS 〈 1 %, ≥ 1 % to ≤49 %; ≥50 %) were represented with 36% pts having ≥50% TPS. Pts received a median of 7.0 (range 1 – 31) pembrolizumab and 11.5 (range 1-22) efti administrations. Responses as per BICR and local read are shown in the table. ORR (local, iRECIST) by different PD-L1 subgroups was 27% for pts with TPS 〈 1%, 39 % for TPS ≥1 %and 54% for ≥50 % TPS. Median PFS (n=36) was 8.2 months while median OS was not yet reached. The most common ( 〉 20 %) treatment emergent adverse events (AEs) were asthenia (47 %), cough (36 %), decreased appetite (36 %), dyspnea (32 %), pruritus (31 %), fatigue (28 %), diarrhea (25 %), anemia (25 %), constipation (25 %) and back pain (22%). Two patients discontinued treatment due to adverse reactions (Grade 4 immune-mediated hepatitis, Grade 3 AST+ALT increase). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in 1st line advanced NSCLC patients across all PD-L1 (TPS) levels. Clinical trial information: NCT03625323. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS6099-TPS6099
    Abstract: TPS6099 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein targeting a subset of MHC class II molecules that mediate antigen presenting cell (APC) and CD8 T-cell activation. Data from a non-randomized, phase II trial of efti plus pembrolizumab (TACTI-002) showed encouraging antitumor activity and manageable safety when given as second-line treatment of patients with recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC). TACTI-003 (NCT04811027) is a multicenter, open label, randomized phase IIb trial to investigate efti plus pembrolizumab in the first-line setting for RM-HNSCC. Methods: A total of 154 patients (pts) are currently being recruited into two cohorts (A+B). In cohort A, pts with tumors that are CPS≥1 will be randomly assigned 1:1 to receive either efti (30 mg subcutaneously Q2W for initial 6 months, thereafter Q3W) plus pembrolizumab (400 mg intravenously Q6W) for up to two years or pembrolizumab alone. Randomization will be stratified by CPS (1-19 vs. ≥ 20) and ECOG PS (0 vs. 1). Pts with tumors that are CPS 〈 1 will receive efti plus pembrolizumab (cohort B). Imaging will be performed every 9 weeks. The primary endpoint (EP) is objective response rate (ORR) by RECIST1.1. Secondary EPs include overall survival, ORR according to iRECIST, time to and duration of response, disease control rate, progression-free survival, occurrence of anti-efti -specific antibodies, safety, and quality of life. Exploratory endpoints comprise biomarkers. The study has been approved by relevant competent authorities, ethic committees and IRBs. Clinical trial information: NCT04811027.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 3100-3100
    Abstract: 3100 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and then CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses than observed with pembrolizumab alone. We hereby report initial results of a phase II trial (NCT03625323). Methods: A predefined number of patients (pts) are recruited into this 3-cohort trial irrespective of PD-L1 expression; part A: 1 st line, PD-X naïve NSCLC; part B: 2 nd line, PD-X refractory NSCLC and part C: 2 nd line PD-X naive HNSCC. The study has a Simon's 2-stage design, with objective response rate (ORR) as primary endpoint. Secondary endpoints include disease control rate, progression free and overall survival, PK, PD and immunogenicity. Additional pts (N2) will be recruited for each part if pre-specified thresholds for ORR are met. Up to 109 pts will be enrolled. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). The study was approved by ethic committees and institutional review boards. Results: Between 04 Mar 19 and 31 Jan 2020, 48 pts were enrolled and evaluated for safety and exposure. The median age was 66 yrs (range 48-84) and 73 % were male. The ECOG was 0 in 50 % and 1 in 50 % of pts, respectively. Pts received a median of 5 (7) and in total 311 (413) pembrolizumab (efti) administrations, respectively. Three pts (6.3 %) discontinued study treatment due to AEs. The most common ( 〉 10%) adverse events (AEs) being cough (31 %), asthenia (23 %), decreased appetite (19 %), fatigue (19 %), dyspnea (17 %), diarrhea (15 %) and constipation 13 %). From part A all pts (n = 17) were evaluated. Eight pts (47 %) had a partial response (iPR) and six (35 %) had stable disease according to iRECIST representing an ORR (DCR) of 47 % (82 %). irPRs were observed in all different PD-L1 groups ( 〈 1%; ≥ 1 % ≤49 %; ≥ 50 %). Ten (10; 59 %) pts are still on therapy (8+ months). In part C stage 1 15/18 pts are evaluable and six (40 %) had an iPR to date. Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in all comer PD-L1 1 st line NSCLC and 2 nd line HNSCC. Stage 2 has opened for both parts. Clinical trial information: NCT03625323 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e18539-e18539
    Abstract: e18539 Background: Clinical trials are essential for enhancing cancer care. Participation is concerning in racial and ethnic minority groups historically under-represented in research. So, it is crucial to note that, despite Hispanics and African-Americans being 18.9% and 13.6% of the US population, each only represents 4% of the patients enrolled in clinical trials. We address effective doctor-patient communication as a fundamental clinical function in establishing an effective doctor-patient relationship, and is vital in delivering high-quality care. In this study, we question whether physician-patient language concordance affects clinical trial enrollment. Methods: The study evaluated 982 patients diagnosed with cancer who consented to experimental clinical trials in a private practice in Houston, Texas, from 2008-2022. All trials had approved language translations for English and Spanish. We used logistic regression to model the probability of treatment, while adjusting for the effects of cancer type, gender, race, ethnicity, and language (same or different as provider). Results: 982 patients with multiple cancer types (hematological, breast, thoracic/respiratory, genitourinary, gastrointestinal, head and neck and CNS) were included in the study. The most represented tumor types were GI (32%), Breast (24%) and Thoracic (23%). 66% of patients were successfully enrolled in an experimental clinical trial and started treatment, and 95% spoke the same language as their providers. 14% of patients spoke a different language than English, Spanish being the most commonly spoken language other than English spoken by the patient and provider. The study has adequate minority representation (Caucasian 45%, Hispanic 30%, African-American 18% and Asian 5%), and equal gender distribution (52% were female). After evaluating the results, it was found that there was no statistically significant association between physician-patient language and enrollment rates (p = 0.3). It was also found that there was no impact when the assessment was divided by tumor type, gender (p = 0.8) or ethnicity. It also evaluated the rate of consent withdrawal, with only 4% of patients withdrawing consent, showing no statistically significant association with language concordance. Conclusions: In conclusion, our study confirms no significant difference in cancer patients’ enrollment rate in clinical trials if there is language concordance between physician and patient. The efforts of the medical workforce to use translators and translated versions of informed consents, surveys or outcome assessments, when available, seem enough for our patients to collect all the information required to agree to continue enrollment. It is required to further evaluate more variables that impact enrollment in minorities to stop this disparity in cancer care.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2552-2552
    Abstract: 2552 Background: MT-6402, an engineered toxin body (ETB) , has been designed to be effective in patients (pts) previously treated with checkpoint inhibitors (CPIs) by utilizing 3 unique mechanisms of action (MOA): (i) remodeling of the tumor microenvironment by elimination of PD-L1 + immunosuppressive cells like myeloid-derived suppressor cells (MDSCs), (ii) direct cell kill of PD-L1 + expressing tumor cells, (iii) delivery of HLA-A*02 restricted cytomegalovirus (CMV) peptide pp65 to PD-L1 expressing cells to direct a CMV specific CD8 T-cell response against the tumor. Methods: Dose escalation continues with MT-6402 (QW in 4-week cycles) in pts with relapsed/refractory PD-L1 + solid tumors. After clearing doses of 16, 24, 32, 42 and 63 µg/kg, 83 µg/kg is being evaluated. Safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamic data are reported. Results: MT-6402 at 63 µg/kg in 1 pt with metastatic nasopharyngeal carcinoma (NPC) who progressed after radiation, chemotherapy, and CPI (PD-L1 CPS=2%, not HLA-A*02) resulted in a PR (63% reduction in target lesion) after 2 cycles. This pt had an increase in CD8/CD4 and immune activation cytokines (IL-2, TNFα, IFNγ) consistent with elimination of MDSCs. A pt with NSCLC (osseous disease only) that had progressed after CPI showed resolution of 3/4 osseous metastases and decreased radiotracer uptake by the remaining bone metastasis. This patient had high PD-L1 tumor expression and HLA-A*02/CMV + . Complete CMV-specific T-cell extravasation was noted by C1D8 consistent with haplotype-specific CMV antigen delivery for presentation on the tumor surface by MHC class I. All cohorts had reductions in peripheral PD-L1 + MDSCs, monocytes and dendritic cells after MT-6402 without effect on PD-L1 - cells with the most depletion at the highest doses. Most pts displayed CD8 + T-cell expansion and elevations of serum IL-2 and TNFα, consistent with PD-L1-mediated immunotolerance. MT-6402 was well tolerated with 2 dose limiting toxicities reported: Grade (G)2 maculopapular rash at 24 µg/kg, G3 IRR at 63µg/kg. No G ≥ 4 AEs occurred. Infusion-Related Reactions in 3 pts (G1, G2, and G3) and Cytokine Release Syndrome (G1 [2 pts] at both 32 and 42µg/kg and G2 [1 pt] at 16µg/kg) occurred. Conclusions: MT-6402 utilizes three PD-L1-targeted and unique MOAs: direct cell-kill, reduced immunosuppression, and increased immunorecognition. As of Feb 2023, 5 dose cohorts have completed. MT-6402 was well tolerated without CLS or payload-derived toxicity as is observed with traditional immunotoxins and ADCs, respectively. A PR in 1 pt with CPI-refractory NPC (CPS 2%, CMV - ) and regression of osseous metastases in a pt with NSCLC (TPS 80%, HLA-A*02/CMV + ) following disease progression on CPI occurred. These results show MT-6402 monotherapy activity though unique MOAs and provide rationale for MT-6402 dose expansion. Clinical trial information: NCT04795713 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 5522-5522
    Abstract: Introduction: Clinical trial accrual and enrollment are essential to break disparities seen in minority populations affected by cancer. Despite Hispanics (HI) being 18.9% of the US population and the fastest-growing minority in the US, they only represent 4% of the patients enrolled in clinical trials. These disparities are often explained by different social determinants of health, but could also be due to decreased perceived interest by oncologists in their participation simply due to lack of English proficiency. Effective doctor-patient communication is vital in establishing a healthy doctor-patient relationship, and is vital in delivering high-quality health care. In this study, we explore whether physician-patient language concordance affects clinical trial enrollment. Methods: We evaluated 233 patients diagnosed with breast cancer who consented to experimental clinical trials in a private Oncology practice in Houston, Texas, from 2008-2022. All trials had approved consent in English and Spanish. We used logistic regression to model the probability of treatment, while adjusting for the effects of cancer type, gender, race, ethnicity, and language concordance. Results: Of the 233 patients with breast cancer, 191(82%) were enrolled in a clinical trial, and 96% of these patients spoke the same language as their providers. 42 patients were not enrolled, with 95% of patients speaking the same language as their provider. There were 209 (90%) patients who spoke English, 22 (9%) were Spanish speakers and 2 (1%) were Arabic speakers. Of the Spanish speakers, 18 were enrolled, with 13 (72%) having language concordance with their provider. The ethnicity was evaluated, resulting in 72 (31%) patients being Hispanics, 55 (24%) African American, 94 (40%) Caucasian, 7 (3%) Asian, 4 (2%) Middle Eastern and 1 (0.4%) American Indian. It also evaluated the rate of consent withdrawal, showing only 6 (3%) patients. After evaluating the results, it was noted that there was no statistically significant association of physician-patient language concordance with enrollment rate (p=0.776). There was also no significant difference in consent withdrawal (p=0.626), and no change associated with gender (p=0.344) or ethnicity when evaluated (p=0.13). Conclusion: In conclusion, our analysis confirms no significant difference in breast cancer patients’ enrollment in clinical trials if there is language concordance between physician and patient. The efforts of the medical workforce to use translators and translated versions of informed consents, surveys or outcome assessments, when available, seem enough for our patients to agree to continue enrollment. Citation Format: Daniela Urueta Portillo, Ana M. Mendoza Sanchez, Nitzia E. Quilantan, Lisa Maria Mendoza Sanchez, Marcela Mazo Canola, Jonathan Gelfond, Julio A. Peguero. Does physician-patient language concordance increase clinical trial enrollment in breast cancer patients?: A real-life study in a majority-minority population. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5522.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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