bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrotinib as neoadjuvant therapy for HER2+ breast cancer: A multicenter, randomized, controlled, phase II trial.
Authors: Ding Xiaowen , Mo Wenju , Xie Xiaohong , Wang Ouchen , Ding Yuqin , Zhao Shuai , He Xiangming , Feng Weiliang , Zou Dehong , Yang Hongjian
Published: June 2021

574

Background: Pyrotinib is a new irreversible tyrosine kinase inhibitor (TKI) which significantly improved the progression-free survival (PFS) of patients with HER2+ metastatic breast cancer (MBC). In this study we aim to investigate the efficacy and safety of pyrotinib in neoadjuvant therapy. Methods: This is an open-label, multicenter, randomized controlled trial. Eligible patients (pts) aged 18–70 years with invasive carcinoma, cT2-3N0-3M0 stage, HER2-positive breast cancer were included. We randomized 34 pts into the treatment group and 33 into the controlled group from 2019-2021. Pts in the treatment group received 6 cycles of pyrotinib 400mg + trastuzumab 6mg/kg (LD 8mg/kg) + docetaxel 75mg/m2 + carboplatin (AUC = 6mg/ml·min) (TCbH+Py) treatment while the controlled group received 6 cycles of trastuzumab 6mg/kg (LD 8mg/kg) + docetaxel 75mg/m2 + carboplatin (AUC = 6mg/ml·min) (TCbH). Total pathologic complete response (tpCR) was defined as no invasive or in situ disease in the breast or axilla (ypT0/Tis, ypN0) and was assigned to be the primary outcome (NCT03756064). Results: 51 cases had completed 6 cycles of neoadjuvant therapy and successfully underwent operation (21 in the treatment group and 30 in the controlled group). In the treatment group, 6 cases have not complete neoadjuvant therapy, 6 cases quitted because of poor compliance and 1 patient has not receive operation yet. For controlled group, 3 patients have not complete neoadjuvant therapy. The tpCR rate in the treatment group is 71.4% (15/21) versus 36.7% (11/30) in the controlled group. A significant difference was determined between the two groups (p < 0.05). All pts achieved an objective response in the treatment group while in the controlled group for about 83.3% (25/30). 4 cases showed stable disease (SD) and 1 case was evaluated as progressive disease (PD) in the controlled group. The most common AE in the treatment group is diarrhoea with grade 3 occurred in 6 cases (28.6%), most of this event limited in the first treatment cycle. In the controlled group 3 pts (10%) occurred grade 3 diarrhoea. Conclusions: In this study TCbH+Py neoadjuvant therapy significantly improved the tpCR rate of HER2+ breast cancer pts for about twice higher than TCbH with a manageable safety. Clinical trial information: NCT03756064.
Effect of neoadjuvant systemic therapy given during window trials on quality metrics in resectable head and neck squamous cell carcinoma.
Authors: Mascarella Marco Antonio , Vendra Varun , Kubik Mark , Sridharan Shaum , Kim Seungwon , Ferris Robert L. , Fenton Moon Jung , Ohr James , Zandberg Dan Paul , Duvvuri Umamaheswar
Published: June 2021

6033

Background: Quality oncologic care, including negative surgical margin status, adequate lymph node yield and prompt initiation of adjuvant treatment, impacts disease control and overall survival in patients with mucosal head and neck squamous cell carcinoma (HNSCC). The aim of this study was to ascertain the effect of neoadjuvant systemic therapy given during window trials on oncologic quality metrics in patients with delayed definitive surgery for a HNSCC. Methods: Treatment-naïve patients with HNSCC participating in one of two window of opportunity clinical trials at UPMC from 2009-2019 were included. Neoadjuvant regimens consisted of one dose of cetuximab (n = 33) or anti-ErbB3 antibody (n = 9) within 28 days of surgery. Sociodemographic, clinical and tumor staging were recorded. The primary outcome was overall oncologic quality, as defined as a composite measure of negative margin status, adequate lymph node yield, completion of adjuvant therapy (if indicated) and time to initiation of adjuvant therapy within 6 weeks of surgery. Secondary outcomes were difference in clinical and pathologic stages and overall survival (OS). Results: A total of 42 patients with a mean age of 57.1 (±10.2) years and median follow-up of 58 months were analyzed. 29 patients had clinical stage IVA disease with 43% (18/42) oral cavity, 36% (15/42) larynx/hypopharynx and 21% (9/42) oropharynx primaries. All patients underwent surgery following neoadjuvant systemic therapy. In 30 patients (71%), all oncologic quality markers were achieved. Pathological downstaging occurred in 21% (9/42) of patients with 4 patients no longer meeting criteria for adjuvant treatment and were observed. 3 patients showed pathological upstaging. The 3-year OS were 76% (95% CI of 63.6-88.4), respectively. Patients with a pathologic downstage migration (64.9%, 95% CI of 49.9-79.8) had higher 5-year OS compared to those without (57.8%, 95% CI of 40.1-76.4, P = 0.046). Conclusions: Most patients receiving neoadjuvant systemic therapy on window trials prior to surgery met all oncologic quality markers. Importantly, even with brief window trial therapy pathologic downstaging was achieved and associated with significantly better overall survival.
Radiomics-based prediction of response to multikinase inhibitors in radioiodine-refractory differentiated thyroid cancer patients.
Authors: Corino Valentina , Colombo Elena , Bologna Marco , Calareso Giuseppina , Mainardi Luca , Cavalieri Stefano , Filippini Daria Maria , Resteghini Carlo , Bergamini Cristiana , Licitra Lisa F. , Locati Laura Deborah
Published: June 2021

6077

Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) represent the first-line treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Currently, no predictive factors for the activity of these drugs are available. We investigated whether radiomics may have a predictive role in this setting. Methods: We retrospectively identified patients (pts) affected by metastatic RR-DTC, treated with TKIs between July 2008 and January 2020 at our Institution, with availability of computed tomography (CT) scans at baseline and after at least 2 courses of TKI. Response to TKIs was evaluated according to RECIST v1.1. Pts with complete or partial response at the first radiological evaluation were considered responders (R), pts with stable or progressive disease non-responders (NR). A dedicated radiologist segmented the target lesions as regions of interest (ROIs). Radiomic features related to multiple categories (shape and size, first order statistics, textural features) were extracted from each ROI and computed using the PyRadiomics library v. 3.0. A semi-supervised form of principal component analysis estimated principal components that were then used for response classification through a k nearest neighbors (kNN) classifier. The quality of the model was assessed through train-validation-test split (55% of the data used as training set, 25% as validation set, 20% as test set), repeated 100 times. Performance of the predictive models was quantified with the mean Area Under the ROC Curve (AUC) obtained in the test set. Results: A total of 51 pts with metastatic RR-DTC who had received lenvatinib (n=37), sorafenib (n=4), axitinib (n=3), or vandetanib (n=7) were analyzed. Median age was 64.6 years, with a male prevalence (72.5%). Metastatic sites were lung (84.3%), bone (35.3%), brain (9.9%). Median time from TKI treatment start to the first radiological evaluation was 2.77 months, 24 pts (47%) were R (all partial responses) and 27 (52.9%) NR. In the radiomic analysis, 851 features were computed and 4-19 principal components were selected. Models’ performance of prediction of early response to TKIs is presented in Table. For each value of AUC, the corresponding 95% confidence interval is reported in brackets. Conclusions: Radiomics predicted the response to TKIs of RR-DTC pts with an accuracy of 71%. Radiomics technique has the potential to enable clinicians to anticipate the probability of response to TKIs at baseline, directing toward the most suitable patient-tailored therapeutic path. Prospective studies may further validate these preliminary findings.[Table: see text]
Patient-reported outcomes (PROs) from a phase II trial of pembrolizumab for HPV-associated papilloma patients with laryngeal, tracheal and/or pulmonary involvement.
Authors: Pai Sara I. , Franco Ramon , Muniappan Ashok , Friedman Aaron D , Park Jong Chul , Campbell Nicholas Paul , Krantz Seth B. , Song Phillip C , Nocon Cheryl , Carroll Thomas L , Faquin William C , Shin Kee-Young , O'Neill Anne M. , Wirth Lori J.
Published: June 2021

6080

Background: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 & 11. RRP proliferates in the respiratory tract impacting breathing, swallowing, and voice and carries a 1-4% risk of malignant transformation.There is no curative therapy for RRP. Given the tolerized host immune response against HPV, the safety and efficacy of pembrolizumab (pembro) as an alternative treatment for this patient population was evaluated in a phase II clinical trial. Patient reported outcomes (PROs) were assessed during the trial to capture the patient perspective of pembro as an alternative to surgery or in office procedures, both standard of care (SOC). Methods: RRP patients who had previously undergone >3 procedures in any year, or with known tracheal or pulmonary involvement prior to study entry were treated with pembro 200mg every 3 weeks. The primary endpoint of the trial was best ‘overall response rate’ (ORR) measured by an endoscopic-based disease burden score (lower score reflects better ‘response’) and/or RECIST 1.1, secondary endpoint included PROs. Twenty-one patients were required to assess the primary endpoint. Most of the QoL surveys used Likert scale to assess PROs (‘never, sometimes, often, most of the time, always’). The percentage reporting ’never’ having an issue with symptom or activity at baseline, 6 months, and at time of ORR (nadir disease burden score) is reported here. Results: Twenty-one patients were accrued. Median age (range) was 45 (19-68), 57% (12/21) were male and 67% (14/21) were white. Questionnaire completion rates were 100% at baseline, 90% at 6 months, and 85% at ORR. Improvement in: social interactions (less difficulty with: physical intimacy [38%,56%,65% reporting ‘never’ at baseline, 6 months, and at ORR respectively]), discussing disease diagnosis [19%,21%,39%]); personal feelings (less depression [14%,32%,33%], less anxiety [5%,16%,22%], less embarrassment [19%,37%,50%]), and work-related absences (less frequently fabricating reasons for work absence due to disease-related treatment [57%,78%,56%] and less utilization of family vacation or FMLA for disease treatment [29%,53%,56%]) were reported. At ORR, 72% (13/18) patients reported that IV infusion was not emotionally burdensome and 78% (14/18) reported it as the preferred treatment relative to their perceived experience with SOC surgery or in office procedures. Conclusions: PRO results show consistent benefit in key aspects of the patient experience with pembro over procedure based SOC further supporting its overall clinical benefit in patients with HPV-associated RRP. Clinical trial information: NCT02632344.
Predictors of clinical trial enrollment and impact on outcome in children and adolescents with acute lymphoblastic leukemia: A population based study.
Authors: Gibson Paul James , Athale Uma H. , Breakey Vicky Rowena , Mittmann Nicole , Bassal Mylene , Silva Mariana , Patel Serina , Zabih Veda , Pechlivanoglou Petros , Pole Jason D. , Gupta Sumit
Published: June 2021

7031

Background: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have shown remarkable improvements in large part due to sequential clinical trials. Concerns however persist around whether access to clinical trials is equitable. It is also unclear whether patient outcomes are improved simply by enrolling on a clinical trial. Our objective was to therefore determine which patient and disease-related factors are associated with enrollment, and whether enrollment was associated with clinical outcomes among children and adolescents with ALL in a single-payer health system in Ontario, Canada. Methods: We included all Ontario patients diagnosed with ALL between 0-18 years of age from 2002-2012 treated at a pediatric center, identified through a provincial pediatric cancer registry. Clinical trial availability was determined by whether each patient’s primary institution had an open frontline trial for which the patient was eligible at the time of their diagnosis, considering individual disease characteristics such as lineage, central nervous system (CNS) status and risk group. Demographic, disease, trial enrolment, and outcome data were obtained through chart abstraction. Logistic regression models determined factors associated with trial enrolment, while Cox proportional hazard models determined factors associated with event-free and overall survival (EFS, OS). Results: Of 858 patients, 693 (81%) were eligible for an open clinical trial at their time of diagnosis. 476 (69%) enrolled on a trial. In adjusted analyses, age > 15 years (odds ratio 0.4 vs. age 5-9, 95th confidence interval (95CI) 0.2-0.8; p = 0.01) and CNS3 disease (OR 0.38 vs. CNS1, 95CI 0.17-0.83; p = 0.01) were significantly associated with decreased likelihood of enrolment, while sex and neighborhood income quintile were not associated with enrolment. Adjusted for disease and demographic factors, clinical trial enrolment was not significantly associated with either EFS (hazard ratio (HR) 1.1, 95CI 0.7-1.7; p = 0.83) or OS (HR 1.3, 95CI 0.7-2.5; p = 0.44). Conclusions: The majority of patients with ALL eligible for available clinical trials at their time of diagnosis were enrolled. While no disparities in enrolment by income status were noted, adolescents were substantially less likely to participate in trials even within pediatric centers. Studies of mechanisms underlying this disparity are warranted in order to design and implement effective interventions targeting increased enrolment rates in this patient population. Our results however also suggest that clinical trial enrolment on its own is not associated with improved outcomes in the context of a single payer health system.
Outcomes with COVID-19 in hematopoietic stem cell transplant and cellular therapy patients.
Authors: Mushtaq Muhammad Umair , Luder Mary , Shahzad Moazzam , Ahmed Nausheen , Abdelhakim Haitham , Bansal Rajat , Balusu Ramesh , Chaudhary Sibgha Gull , DeJarnette Shaun , Divine Clint , Kribs Robert , Shune Leyla , Singh Anurag K , Abhyankar Sunil H. , Ganguly Siddhartha , McGuirk Joseph
Published: June 2021

7033

Background: The Coronavirus Disease 2019 (COVID-19) has caused over 25 million infections in the US with over 0.4 million deaths. Hematogenic stem cell transplant (HCT) or cellular therapy (CT) recipients have a high risk of mortality with COVID-19 due to profound immune dysregulation. We aimed to assess the outcomes with COVID-19 in HCT/CT recipients. Methods: A single-center prospective study was conducted, including all (n=40) adult HCT/CT patients who were diagnosed with COVID-19 at the University of Kansas from Apr 2020 to Jan 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using chi-square and t-test, and logistic regression analyses were conducted. Results: The study included 40 COVID-19 patients (72.5% Oct 2020-Jan 2021), including allogeneic HCT (n=25), autologous HCT (n=13) and CAR-T CT (n=2) with median time since HCT/CT of 12.4 (1-201.9), 37.2 (0.4-118.7), and 3.8 (2.8-4.8) months. Seventy percent were Caucasians and 17.5 were Hispanics. Primary hematologic malignancy was myeloid (37.5%), lymphoid (35%) or plasma cell disorder (27.5%). Myeloablative conditioning was performed in 65% of patients. Donors were autologous (37.5%), matched sibling (17.5%), matched unrelated (22.5%) and haploidentical (22.5%). COVID-19 was mild (42.5%), moderate (42.5%) or severe (15%). Clinical findings included pneumonia (62.5%), hypoxia (25%) and ICU admission (17.5%) while therapies included remdesivir (47.5%), convalescent plasma (40%), dexamethasone (25%) and monoclonal antibodies (17.5%). Concurrent cancer treatment, other infections and active GVHD were reported in 25% (all myeloma), 20% and 32.5% of patients. After a median follow-up of 74 days (7-269), the mortality rate was 12.5% in all patients and 20% in allo-HCT patients. Significant predictors of COVID-19 severity included allogeneic HCT, concurrent immune suppression and elevated inflammatory markers. (Table). Conclusions: Hematopoietic stem cell transplant recipients have an increased risk of mortality with COVID-19. Our findings confirm the need for vaccination prioritization, close monitoring, and aggressive treatment in HCT/CT patients.[Table: see text]
The effect of body mass index on efficacy and safety of bosutinib or imatinib in patients with newly diagnosed chronic myeloid leukemia.
Authors: Brümmendorf Tim H. , Cortes Jorge E. , Busque Lambert , Gambacorti-Passerini Carlo , Stenke Leif , Viqueira Andrea , Leip Eric , Purcell Simon , Deininger Michael W
Published: June 2021

7037

Background: Bosutinib (BOS) is approved for the treatment (Tx) of Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed Ph+ chronic phase (CP) CML. Body mass index (BMI) was shown to influence Tx response with front-line dasatinib vs imatinib (IMA). We report the efficacy and safety of BOS and IMA by BMI in patients (pts) with newly diagnosed CP CML. Methods: In the open-label BFORE trial, pts were randomized to receive 400 mg once daily BOS or IMA. Outcomes were assessed according to baseline BMI ≥25 or = 25 kg/m2. This post hoc analysis was based on the final 5-y analysis (database lock: June 12, 2020). Results: In the BOS and IMA arms, respectively, 149 (56.4%) vs 115 (43.6%) pts and 145 (54.3%) vs 122 (45.7%) pts had BMI ≥25 vs = 25. In both the BOS and IMA arms, median Tx duration and time on study was 55 mo for pts with BMI ≥25 or = 25; respective median dose intensity was 394 vs 393 mg/d and 400 vs 400 mg/d. Molecular response (MR) rates are shown in the table. Cumulative incidence of major MR was similar in pts with ≥25 vs = 25 receiving BOS (HR 0.99; 95% CI 0.74−1.31) or IMA (HR 1.09; 95% CI 0.81−1.47). Event-free survival (EFS) and overall survival (OS) rates at 60 mo are shown in the table. Most common reasons for Tx discontinuation were adverse events (AEs) (BOS 28.2 vs 20.0%; IMA 13.3 vs 10.7%) and lack of efficacy (BOS 5.4 vs 5.2%; IMA 16.1 vs 19.8%). In pts with BMI ≥25 vs = 25, dose reductions and interruptions due to Tx-emergent AEs (TEAEs) occurred in 43.6 % vs 46.2% and 66.4% vs 69.7% of pts with BOS and 24.5% vs 24.6% and 40.6% vs 50.8% with IMA. Any grade TEAEs in ≥30% of pts with BMI ≥25 vs = 25 were diarrhea (73.8 vs 73.1%), nausea (40.9 vs 31.9%), thrombocytopenia (30.9 vs 41.2%), increased alanine (37.6 vs 28.6%) and aspartate aminotransferase (30.2 vs 20.2%) with BOS and diarrhea (49.0 vs 29.5%), nausea (46.2 vs 37.7%), muscle spasms (33.6 vs 26.2%), neutropenia (14.7 vs 32.0%) and thrombocytopenia (10.5% vs 30.3%) with IMA. Conclusions: Efficacy of BOS was consistent in pts with BMI ≥25 or = 25; however, with IMA a low (vs high) BMI appeared to be associated with worse survival outcomes. Differences in certain TEAEs were observed between BMI subgroups in both treatment arms. Clinical trial information: NCT02130557. [Table: see text]
Clinical characteristics, treatment patterns, and overall survival of real-world patients with idiopathic multicentric Castleman disease.
Authors: Cohen Aaron B. , Swaminathan Akshay , Wang Xiaoliang , Zamora Stephen , Repucci Michael A , Kelly Jonathan , Hannan Mark D , Sepler Daniel , Sridharma Suganya , Orlando Abigail , Leybovich Barry , Fajgenbaum David
Published: June 2021

7048

Background: Castleman disease (CD) has three subtypes: Unicentric (UCD), Human herpesvirus-8 associated multicentric (HHV-8 MCD) and idiopathic multicentric (iMCD). Outcomes for patients with iMCD are poor and treatment options are limited, with only one FDA-approved therapy (siltuximab in April 2014). Further, the lack of CD-specific ICD codes until 2017 has limited real-world evaluation. We identified iMCD patients in an electronic health record (EHR)-derived dataset and described their clinical characteristics, treatment patterns, and real-world overall survival (rwOS). Methods: Patients with a possible diagnosis of CD as of 8/31/20 were identified from the nationwide deidentified Flatiron Health EHR-derived database using patient-level structured data (e.g., ICD-9/10 codes) and unstructured data (e.g., clinician notes), curated via technology-enabled manual abstraction to confirm CD diagnosis and treatments received. Descriptive statistics summarized patient characteristics and treatment patterns. Patients without structured data within 90 days after diagnosis were excluded from treatment patterns analyses. 5-year rwOS rate was estimated from diagnosis date using the Kaplan-Meier estimator. Results: 747 patients with possible CD were identified, of whom 453 were confirmed to have CD by abstraction (172 UCD, 100 iMCD, 36 HHV-8 MCD, and 145 unclassified). IMCD patients were predominantly female (53%), white (58%), and treated at community sites (70%). Of the 52 iMCD patients with evidence of structured data within 90 days after diagnosis and who had at least one documented line of therapy, the most common first-line therapies were siltuximab-based therapy (42.3%), rituximab monotherapy (36.5%), and chemotherapy-based treatment (13.5%). Among 28 iMCD patients with evidence of second-line therapy, the most common treatment was rituximab monotherapy (35.7%). Among 60 iMCD patients diagnosed on or after siltuximab approval in April 2014 (including those without evidence of any treatment), 26 (43%) received siltuximab at some point. 5-year rwOS rate for the 100 iMCD patients was 75% [95% CI: 63-89%]. Conclusions: This is the first study to utilize a large EHR-derived database to describe characteristics, treatment patterns, and overall survival of iMCD patients in real-world practice. Less than half of iMCD patients diagnosed on or after the date of FDA approval for siltuximab received it at some point. Future work should focus on characterizing the drivers of poor patient outcomes.
Polatuzumab vedotin + obinutuzumab + venetoclax in patients with relapsed/refractory (R/R) follicular lymphoma (FL): Primary analysis of a phase 1b/2 trial.
Authors: Bannerji Rajat , Yuen Sam , Phillips Tycel Jovelle , Arthur Christopher , Isufi Iris , Marlton Paula , Seymour John Francis , Corradini Paolo , Molinari Annalia , Gritti Giuseppe , Emmons Robert , Hirata Jamie , Musick Lisa , Saha Sourish , Croft Brandon , Flowers Christopher
Published: June 2021

7534

Background: Polatuzumab vedotin (Pola) + obinutuzumab (G) demonstrated activity and tolerability in a Phase 1b/2 trial of patients (pts) with R/R FL (Phillips, et al. Blood 2016). Preclinical studies with venetoclax (Ven) showed that concurrent treatment with Pola promotes MCL-1 degradation, a known mechanism of resistance to Ven, and enhances in vivo anti-tumor efficacy (Amin, et al. AACR 2020). Here, we report the primary safety/efficacy analysis with Pola-G-Ven in a Phase 1b/2 study of pts with R/R FL (GO29833; NCT02611323). Methods: Pts received induction treatment every 21 days (D) x six cycles (C) of: Pola 1.4–1.8mg/kg intravenously (IV) in dose escalation (DE) or recommended Phase 2 dose (RP2D) on D1; G 1000mg IV (C1: D1, D8, D15; C2–6: D1); and oral Ven 200–800mg (DE or RP2D; D1–21). Pts with complete response/partial response/stable disease (CR/PR/SD) at end of induction (EOI) received maintenance with G (1000mg on D1 every 2 months [mo] for 24 mo) and Ven (200–800mg daily) for 8 mo. Primary endpoints were safety/tolerability and positron emission tomography (PET)-CR rate at EOI by independent review committee (IRC) using modified Lugano criteria. Results: At the primary analysis (Oct 05, 2020), 74 pts were enrolled. Median pt age was 64 years (range 36–78); male (57%); Ann Arbor Stage III–IV (86%); FL International Prognostic Index high risk ≥3 (55%); bulky disease ≥7cm (16%); prior lines of therapy ≥2 (74%); refractory to: last prior therapy (51%), any prior anti-CD20 therapy (55%), both anti-CD20 therapy and an alkylating agent (double refractory; 55%). Grade 3–4 adverse events (AEs) were experienced by 73% of pts; most commonly, neutropenia (39%), thrombocytopenia (19%), and infections (16%; mainly pneumonia). AEs led to dose reduction in 38% and interruption in 68% of pts (mainly modifications to Ven). One fatal AE was reported (pneumonia). In total, 49 pts were treated at RP2D (Pola 1.8mg/kg + Ven 800mg) and were evaluable for efficacy. PET-CR rate at EOI by IRC was 57% (Table). With a median follow-up of 14.4 mo (range 8.2–28.4), the 12-mo progression-free survival (PFS) was 73% (95% confidence interval: 59.4–86.9). Median PFS was not reached. Conclusions: The safety profile of Pola-G-Ven is consistent with the known profiles of the individual drugs. Response rates at EOI with Pola-G-Ven are encouraging in this R/R FL patient population. Additional follow-up is needed to assess PFS benefit during maintenance treatment and beyond. Clinical trial information: NCT02611323. [Table: see text]
Assessing financial difficulty in patients with multiple myeloma: Preliminary results of ALLIANCE A231602CD.
Authors: Conti Rena M. , McCue Shaylene , Dockter Travis , Rapkin Bruce D. , Dusetzina Stacie , Bennett Antonia Vickery , Gracia Gabriela , Johnson Michelle E. , Martin Sarah A. , Chang George J. , Richardson Paul G. , Behrens Robert J. , Weiss Elisa S.
Published: June 2021

8031

Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.
Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf).
Authors: Terpos Evangelos , Badros Ashraf , Popat Rakesh , Rodríguez-Otero Paula , Farooq Asim , Jeng Bennie , Degli Esposti Simona , Lewis Eric , Gupta Ira , Opalinska Joanna , Palumbo Antonio , Trudel Suzanne
Published: June 2021

8033

Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]
Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study.
Authors: Manier Salomon , Kansagra Ankit J. , Anderson, Jr Larry D. , Berdeja Jesus G. , Jagannath Sundar , Lin Yi , Lonial Sagar , Shah Nina , Raje Noopur S. , Siegel David Samuel DiCapua , Oriol Albert , Truppel-Hartmann Anna , Rowe Everton , Patel Payal , Agarwal Amit , Campbell Timothy B. , Rodríguez-Otero Paula , Munshi Nikhil C. ,   on behalf of the KarMMa Study Investigators
Published: June 2021

8036

Background: Ide-cel, a BCMA-directed CAR T cell therapy, showed promising efficacy in patients (pts) with RRMM in the KarMMa study with an ORR of 73% and a CRR of 33% across target doses of 150–450 × 106 CAR+ T cells (Munshi NC, et al. J Clin Oncol 2020;38[suppl 15]. Abstract 8503). Associations of neurotoxicity (NT) with pt and disease characteristics, pt management, and impact on outcomes in the KarMMa study are reported here. Methods: Enrolled pts were triple-class exposed and refractory to their last regimen, with ide-cel given at target doses of 150, 300, or 450 × 106 CAR+ T cells after lymphodepletion (NCT03361748). Investigator-identified NT events were captured under the single preferred term of neurotoxicity and graded according to NCI CTCAE v4.03. Events were managed with corticosteroids (CS), anakinra (ANR), and tocilizumab (Toci) as needed. Results: Of 128 pts treated with ide-cel, NT was reported in 23 (18%); 12 pts (9%) had maximum grade (gr) 1 NT, 7 (5%) had gr 2, and 4 (3%) had gr 3. No gr 4 or 5 NT occurred. Most baseline characteristics were similar in pts with and without NT, including stage III disease (22% and 15%), high-risk cytogenetics (39% and 34%), and extramedullary disease (35% and 40%); exceptions were high tumor burden (65% and 48%) and sex (48% and 62% men). NT (any gr/gr 3) occurred in 0%/0%, 17%/1%, and 20%/6% of pts at doses of 150, 300, and 450 × 106 CAR+ T cells. Median time to onset was similar regardless of gr, and there were no late-onset events (Table). NT was managed with CS in 10 pts (43%), Toci in 3 (13%), and ANR in 1 (4%). Median (range) time to first use of CS was 2 d (1–6). ORR and DOR were similar in pts with and without NT (Table). All NT occurred in the proximity of cytokine release syndrome (CRS) events with the start date of NT events either overlapping with or occurring within 1 wk of the start of a CRS event. Conclusions: NT occurred early in the KarMMa study, was generally of short duration, and was mostly gr 1/2 with no gr ≥4 events. All NT was proximal to CRS. Pts with NT had a favorable ORR after ide-cel treatment. These results continue to demonstrate the durable efficacy and tolerability of ide-cel in pts with RRMM. Clinical trial information: NCT03361748. [Table: see text]
Ixazomib (IXA), carfilzomib (CAR), elotuzumab (ELO) or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) versus LEN+DEX only in relapsed/refractory multiple myeloma (R/R MM): A comparative cost-effectiveness analysis.
Authors: Obeng-Kusi Mavis , Arku Daniel , Alrawashdh Neda , Choi Briana , Alkhatib Nimer S. , McBride Ali , Abraham Ivo
Published: June 2021

8043

Background: IXA, CAR, ELO and DARin combination with LEN+DEXhave been found superior in efficacy compared to LEN+DEX in the management of R/R MM. Applying indirect treatment comparisons from a network meta-analysis (NMA), this economic evaluation aimed to estimate the comparative cost-effectiveness and cost-utility of these four triplet regimens in terms of progression-free survival (PFS). Methods: In the absence of direct treatment comparison from a single clinical trial, NMA was used to indirectly estimate the comparative PFS benefit of each regimen. A 2-state Markov model simulating the health outcomes and costs was used to evaluate PFS life years (LY) and quality-adjusted life years (QALY) with the triplet regimens over LEN+DEX and expressed as the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). Probability sensitivity analyses were conducted to assess the influence of parameter uncertainty on the model. Results: The NMA revealed that DAR+LEN+DEX was superior to the other triplet therapies, which did not differ statistically amongst them. As detailed in the Table, in our cost-effectiveness analysis, all 4 triplet regimens were associated with increased PFSLY and PFSQALY gained (g) over LEN+DEX at an additional cost. DAR+LEN+DEX emerged the most cost-effective with ICER and ICUR of $667,652/PFSLYg and $813,322/PFSQALYg, respectively. The highest probability of cost-effectiveness occurred at a willingness-to-pay threshold of $1,040,000/QALYg. Conclusions: Our economic analysis shows that all the triplet regimens were more expensive than LEN +DEX only but were also more effective with respect to PFSLY and PFSQALY gained. Relative to the other regimens, the daratumumab regimen was the most cost-effective.[Table: see text]
Comparison of outcomes with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus real-world standard of care (RW SOC) for patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM).
Authors: Martin Thomas G. , Krishnan Amrita Y. , Yong Kwee , Weisel Katja , Mehra Maneesha , Nair Sandhya , Qi Keqin , Londhe Anil , Diels Joris , Crivera Concetta , Jackson Carolyn Chang , Olyslager Yunsi , Vogel Martin , Schecter Jordan Mark , Banerjee Arnob , Valluri Satish , Usmani Saad Zafar , Berdeja Jesus G. , Jagannath Sundar
Published: June 2021

8045

Background: Pts with RRMM who are triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and an anti-CD38 antibody) cycle through multiple salvage regimens with progressively worse outcomes. CARTITUDE-1 (NCT03548207) is a single-arm phase 1b/2 study evaluating cilta-cel, a chimeric antigen receptor T-cell therapy with 2 B-cell maturation antigen–targeting single-domain antibodies, in pts with RRMM who received ≥3 prior lines of therapy (LOT) or were double refractory to an IMiD and PI, were triple-class exposed, had ECOG score of 0 or 1, and had disease progression ≤12 mo after the last LOT. Here, we compare efficacy outcomes for pts who received cilta-cel in CARTITUDE-1 (N = 97) with pts treated with SOC in a synthetic cohort from RW clinical practice. Methods: The Flatiron database, a primarily US community-based MM registry (Sep 2020 data cutoff), was used to identify a RW pt cohort who met CARTITUDE-1 (Sep 2020 data cutoff) eligibility criteria, including organ function. Progression-free/overall survival (PFS/OS) were compared between the cilta-cel–treated US pts and RW SOC cohort, using inverse probability of treatment (tx) weighting (IPTW) propensity scores adjusting for unbalanced baseline covariates of prognostic significance. Sensitivity analyses were conducted using multivariate Cox regression models and propensity score matching. Results: Baseline characteristics were similar between the 2 cohorts after propensity score weighting (Table). SOC tx regimens in the RW cohort primarily included pomalidomide (33%), carfilzomib (32%), daratumumab (13%), elotuzumab (16%), and ixazomib (8%). Pts had improved PFS and OS with cilta-cel (N = 97; median follow-up 12.4 mo) vs RW SOC (N = 196; median follow-up 9.2 mo) with a reduction in risk of progression/death and death by 84% and 78%, respectively (Table). Cilta-cel treatment benefit was robust across sensitivity analyses. Conclusions: Cilta-cel shows significantly better efficacy outcomes over RW SOC for PFS and OS, highlighting its potential as an effective tx option in pts with triple-class exposed RRMM. Clinical trial information: NCT03548207. [Table: see text]
Impact of socioeconomic disparities on diagnosis and overall survival in small cell lung cancer: A National Cancer Database analysis.
Authors: Roof Logan , Wei Wei , Tullio Katherine , Pennell Nathan A. , Stevenson James
Published: June 2021

8515

Background: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses in the United States. The demographics of this disease have evolved over time; in the 1970s 28% of patients with SCLC were female, while in the early 2000s, 50% were female. Remarkable differences in incidence, mortality rates, and trends by race and geographic location have also been noted. There has been a paucity of data regarding changes in epidemiology and patient demographics in SCLC since the early 2000s. Given recent treatment advances, the impact these factors have on patient outcomes for SCLC requires further evaluation. Methods: We identified all patients with SCLC in the NCDB from 2004 to 2016. Differences in demographic, disease, and treatment characteristics were assessed by year of diagnosis using Chi-square test. The effect of age, race, insurance status, income, distance to treatment center, and education level on overall survival (OS) was assessed by log-rank test. Results: There were 137,253 cases of SCLC diagnosed in the NCDB between 2004-2010 and 124,796 cases between 2011-2016. Patients diagnosed after 2010 were significantly older, had more comorbidities, had more stage IV disease, were more frequently treated at academic centers, more commonly had government primary payer insurance, and lived significantly further away from their treatment center. There were significant differences in gender, race/ethnicity groups, education level, and residence area, with more females, more African Americans, more patients without a high school diploma, and more rural patients diagnosed after 2010. OS in general improved between the two time periods, with median OS of 8.41 months (95% CI: 8.34-8.48%) and 5-year OS rate of 6.8% (95% CI: 6.6-6.9%) in patients diagnosed between 2004-2010 and median OS of 8.61 months (95% CI: 8.54-8.67%) and 5-year OS rate of 8.7% (95% CI: 8.5-8.9%) in patients diagnosed after 2010, despite an increase in stage IV disease in the latter group. Some of the differences in demographics were associated with changes in OS. Older patients, male patients, Caucasian patients, patients with stage IV disease, patients with government primary payer insurance, and rural patients all had significantly worse OS. Patients without comorbidities and patients treated at an academic center had significantly better OS. OS was found to significantly increase as both income and education level increase. Conclusions: SCLC continues to be a frequent cancer diagnosis. Despite improvement in overall survival during the time frame studied, there were significant disparities noted in key demographics that negatively affect access to healthcare resources, including rural communities, distance to an academic center, income, insurer, and education level. Collective efforts to impact these disparities will likely lead to improved outcomes for patients with SCLC.
Association of high level of plasma tissue factor activity with venous thromboembolism and early death in lung cancers.
Authors: Doubre Helene , Monnet Isabelle , Azarian Reza , Girard Philippe , Meyer Guy , Trichereau Julie , Devillier Philippe , Van Dreden Patrick , Couderc Louis-Jean , Chouaid Christos , Vasse Marc
Published: June 2021

8532

Background: Venous thromboembolism (VTE) is associated with tumor aggressiveness and mortality in cancers. Tissue Factor is the main activator of the coagulation but its variations in lung cancers (LC) have been less studied than D-dimers (DDi). We assessed plasma Tissue Factor Activity (TFa) and DDi and VTE events and mortality in patients with LC. Methods: This prospective study included patients, from 5 hospitals, recently diagnosed LC, without prior VTE or anticoagulant therapy within the last 2 months. Clinical and tumor data, Khorana score (KS), VTE events and overall survival (OS) were assessed (follow up 2 years). Blood samples were collected before any cancer treatment (V1): DDi (HemosIL) and TFa (chromogenic assay, Diagnostica Stago) were analyzed in a central lab. Independent nonparametric tests were used for group comparisons. A relevant clinical threshold of both markers was determined :1500 μg/ml for DDi and 1.2 ng/ml for TFa. Early death was compared using Cox model and Kaplan Meier curves and logrank tests. All tests were two-tailed tests and 0.05 was considered as significant. Results: Between 12/2014 and 01/2017, 302 consecutive patients (pts) were included (mean age 64 years, 61% males, 89% smokers, 85% NSCLC, 67% stage IV). At V1, TFa levels increased with cancer stage (p = 0.004) but not DDi. VTE incidence was 13,9%: 39 events (62% incidental and 51% pulmonary embolism) with 33 events within 6 months. KS failed to predict VTE (KS > 3 in 23% of the pts in VTE group vs 21% of the 302 pts, p = 0.42). DDi and TFa levels were not significantly different in VTE pts than in no VTE pts. But, a TFa > 1.2 ng/ml was significantly predictive in occurrence of VTE within the first 6 months (57.6% of the VTE pts vs 38.8% of no VTE pts, p = 0.04), and also within the first year (p = 0.03). Median OS was 17,6 months (m) in VTE pts and 19.5 m in no VTE pts (p = 0,97). Compared to survivors, higher levels of DDi and TFa were observed for the 38 pts who died within 6 months : 1.82 vs 0.67 μg/ml (p < 0.001) and 1.95 vs 0.33 ng/ml (p < 0.001) respectively. These differences were observed for the 97 pts who died during the first year, too. With thresholds of TFa > 1.2 ng/ml and DDi > 1500 μg/ml, median OS was significantly shorter: 14.4 m vs > 29.8 m ( p < 0,001) and 13.8 m vs 22.6 m (p < 0.001), respectively. Conclusions: High TFa level discriminates a population with high risk to VTE and early death in LC. This biomarker could take place in a predictive score. Clinical trial information: NCT02853188.
The clinical efficacy of olaparib monotherapy or combination with ceralasertib (AZD6738) in relapsed small cell lung cancer.
Authors: Park Sehhoon , Mortimer Peter G. , Smith Simon , Kim Heejung (Rosa) , Jung Hyun Ae , Sun Jong-Mu , Ahn Jin Seok , Ahn Myung-Ju , Park Woong-Yang , Lee Se-Hoon , Park Keunchil
Published: June 2021

8562

Background: The molecular profiling of small cell lung cancer (SCLC) has demonstrated a high incidence of genomic alterations in cell cycle-related genes and DNA damage and response (DDR) pathways, which correlates with devastating clinical outcomes of SCLC. Using two small molecules targeting the DNA repair pathway, olaparib (PARP inhibitor) and ceralasertib (ATR inhibitor), we evaluated their clinical efficacy in monotherapy or in combination, in relapsed SCLC. Methods: As part of the phase II biomarker-driven umbrella study in SCLC (SUKSES), patients who failed prior platinum-based regimen were enrolled and allocated based on their genomic alterations. Patients with mutations harboring HR pathway gene mutation not limited to BRCA 1 or 2, ATM deficiency or MRE11A mutations were allocated to the olaparib monotherapy (SUKSES-B, NCT03009682). As an biomarker non-matched arm, biomarker unselected patients were also allowed to receive olaparib and ceralasertib arm (SUKSES-N2, NCT0328607). The primary endpoint was objective response rate (ORR), and two-stage Simon’s design was used. Results: Based on pre-defined protocol criteria, both arms terminated at stage 1. In the olaparib monotherapy arm (SUKSES-B, n = 15), ORR was 6.7%, and disease control rate (DCR) was 26.7%, 1 partial response (PR), and 3 stable diseases (SD). Median progression-free survival (PFS) was 1.25 months (95% confidential interval [CI] 1.18–NA), and median overall survival (OS) was 8.56 months (95% CI, 6.62–NA). Adverse events that led to treatment discontinuation (n = 2 total, 13.3%) were drug related grade 3 renal impairment, thrombocytopenia, and grade 2 anemia. A patient with confirmed PR showed a tumor volume decrease of 37% compared to the baseline, and a splicing site mutation in BRCA2 was identified from deep target sequencing. In the olaparib and ceralasertib treatment arm (SUKSES-N2, n = 26), ORR was 3.8% (n = 1) and DCR was 42.3% (n = 11). Median PFS was 2.75 months (95% CI 1.77–5.44), and OS was 7.18 months (95% CI 5.97-10.79). Three patients discontinued treatment due to drug related grade 5 pneumonia, grade 3 drug-induced pneumonitis and grade 2 anemia. The most common adverse events for the combination were anemia (n = 11, 42.3%), followed by thrombocytopenia (n = 6, 23.1%). A patient with confirmed PR with a 43% decreases in tumor volume compared with baseline had a mutation in TP53. Conclusions: Targeting the DDR pathways with olaparib as single agent or in combination with ceralasertib demonstrated early signal of efficacy in relapsed SCLC patients with a tolerable safety profile. Clinical trial information: NCT03009682, NCT0328607.