bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival from pembrolizumab (pembro) completion and pembro retreatment: Phase III KEYNOTE-006 in advanced melanoma.
Authors: Long Georgina V. , Schachter Jacob , Arance Ana , Grob Jean-Jacques , Mortier Laurent , Daud Adil , Carlino Matteo S. , Ribas Antoni , McNeil Catriona M. , Lotem Michal , Larkin James M. G. , Lorigan Paul , Neyns Bart , Blank Christian U. , Petrella Teresa M. , Hamid Omid , Jensen Erin , Krepler Clemens , Diede Scott J. , Robert Caroline 
Published: May 2020

10013 Background: 5-year follow-up of the phase 3 KEYNOTE-006 study (NCT01866319) showed pembro improved OS vs ipilimumab (ipi) in patients (pts) with advanced melanoma. 3-y OS rate from pembro completion for pts who completed 2 y of pembro was 93.8%. Results with 8 mo of additional follow-up are presented to inform clinical care. Methods: Eligible pts with ipi-naive advanced melanoma, ≤1 prior therapy for BRAF-mutant disease, and ECOG PS 0 or 1 were randomized to pembro 10 mg/kg Q2W or Q3W for ≤2 y or ipi 3 mg/kg Q3W for 4 doses. Pts discontinuing pembro with CR, PR, or SD after ≥94 weeks were considered pts with 2-y pembro. Pts who stopped pembro with SD, PR or CR could receive ≤12 mo of additional pembro (2nd course) upon disease progression if still eligible. ORR was assessed per immune-related response criteria by investigator review. OS was estimated using the Kaplan-Meier method. Pembro arm data were pooled. Post hoc ITT efficacy analyses are shown. Results: Median follow-up from randomization to data cutoff (Jul 31, 2019) was 66.7 mo in the pembro and 66.9 mo in the ipi arms. OS outcomes are shown in Table. For the 103 pts with 2-y pembro (30 CR, 63 PR, 10 SD), median follow-up from completion was 42.9 mo (95% CI, 39.9-46.3).Median DOR was not reached. 36-mo OS from pembro completion was 100% (95% CI, 100.0-100.0) for pts with CR, 94.8% (95% CI, 84.7-98.3) for pts with PR, and 66.7% (95% CI, 28.2-87.8) for pts with SD. 15 pts received 2nd-course pembro; BOR in 1st course was 6 CR, 6 PR, and 3 SD. Median time from end of 1st course to start of 2ndcourse was 24.5 mo (range, 4.9-41.4). Median follow-up in pts who received 2nd-course pembro was 25.3 mo (range, 3.5-39.4). Median duration of 2nd-course pembro was 8.3 mo (range, 1.4-12.6). BOR on 2ndcourse was 3 CR, 5 PR (ongoing responses, 7 pts), 3 SD (ongoing, 2 pts), and 2 PD (1 death); 2 pts pending. Conclusions: Pembro improves the long-term survival vs ipi in pts with advanced melanoma, with all pts who completed therapy in CR still alive at 5 years. Retreatment with pembro at progression in pts who stopped at SD or better can provide additional clinical benefit in a majority of pts. Clinical trial information: NCT01866319. [Table: see text]
TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded).
Authors: Tung Nadine M. , Robson Mark E. , Ventz Steffen , Santa-Maria Cesar Augusto , Marcom Paul Kelly , Nanda Rita , Shah Payal D , Ballinger Tarah Jean , Yang Eddy Shih-Hsin , Melisko Michelle E. , Brufsky Adam , Vinayak Shaveta , Demeo Michelle , Jenkins Colby , Domchek Susan M. , Wulf Gerburg M. , Krop Ian E. , Wolff Antonio C. , Winer Eric P. , Garber Judy Ellen ,   Translational Breast Cancer Research Consortium
Published: May 2020

1002 Background: Olaparib, a PARP inhibitor, is approved for HER2-negative MBC in g BRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated study, assessed the response to olaparib in MBC patients with sBRCA1/2 mutations or g/s mutations in DDR-pathway genes other than BRCA1/2. Methods: Eligibility included: MBC with measurable disease; progression on < 2 metastatic chemotherapy regimens. Prior PARP inhibitor or progression on platinum was not allowed. Cohort 1 included patients with germline mutations in non- BRCA1/2 DDR-pathway genes. In Cohort 2 were those with somatic mutations in these genes or BRCA1/2; germline testing was required only to exclude a gBRCA mutation if a s BRCA mutation was present. Patients received olaparib 300 mg bid until progression or unacceptable toxicity. For each cohort, a single-arm Simon two-stage design was used with 13 then 14 patients in the 1st and 2nd stages, respectively. The null hypothesis within each cohort [≤ 5% objective response rate (ORR)] would be rejected if > 4 responses were seen at the end of stage 2. Secondary endpoints include clinical benefit rate, progression-free survival, and duration of response. Results: 54 patients enrolled from March 2018 to Jan 2020; 1 ineligible s BRCA2 was excluded. Median age was 59 yrs (range: 30-87). 40 patients had ER+ HER2-, 3 HER2+, and 10 TNBC. 87% had a mutation in PALB2, s BRCA1/2, ATM or CHEK2. ORR was 29.6% (8/27, 90%-CI: 15.6%-47.1%) in Cohort 1 and 38.5% (10/26, 90%-CI: 22.5%-56.4%) in Cohort 2. Responses were gene specific (Table): g PALB2 and s BRCA mutations predicted response; no responses were seen with only a CHEK2 or ATM mutation. To date, responses as long as 16.4 months have been observed. Responses were seen in all subtypes: 5/10 TNBC, 1/3 HER2+, 12/40 ER+ HER2-. 11 responses occurred after prior CDK4/6 inhibitor. In June 2020, final data for confirmed ORR and secondary endpoints will be reported. Conclusion: In this proof-of-principle study, single-agent olaparib successfully met its primary endpoint in both cohorts. Activity was seen largely in patients with MBC and s BRCA1/2 or g PALB2 mutations but not with ATM or CHEK2 mutations. Clinical trial information: NCT03344965 . [Table: see text]
Pyrotinib or lapatinib plus capecitabine for HER2+ metastatic breast cancer (PHOEBE): A randomized phase III trial.
Authors: Xu Binghe , Yan Min , Ma Fei , Hu Xi-Chun , Feng Ji Feng , Ouyang Quchang , Tong Zhongsheng , Li Huiping , Zhang Qingyuan , Sun Tao , Wang Xian , Yin Yongmei , Cheng Ying , Li Wei , Zhu Xiaoyu , Chen Chunxia , Zou Jianjun ,   The PHOEBE Group
Published: May 2020

1003 Background: Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine showed clinically meaningful benefits and acceptable tolerability in patients (pts) with HER2+ metastatic breast cancer (MBC) in phase 1 and 2 studies. Methods: This open-label, multicenter, randomized phase 3 study enrolled HER2+ MBC pts after trastuzumab and taxanes, and/or anthracyclines. Up to two prior lines of chemotherapy (chemo) for metastatic disease were allowed. Pts were randomly assigned (1:1) to receive pyrotinib 400 mg or lapatinib 1250 mg qd continuously plus capecitabine 1000 mg/m2 bid on days 1–14 of 21-day cycles. The primary endpoint was progression-free survival (PFS) per blinded independent central review. Results: From Jul 2017 to Oct 2018, 267 pts were randomized to the pyrotinib (n=134) or lapatinib (n=133) arm. One pt in the lapatinib arm did not receive study treatment and was excluded from analyses. 42.5% and 34.8% of pts in the pyrotinib and lapatinib arm had no prior chemo for metastatic disease, 41.8% and 49.2% had one prior line, and 15.7% and 15.9% had two lines. At the planned interim analysis, the median PFS was 12.5 months (95% CI 9.7–not reached) with pyrotinib plus capecitabine vs 6.8 months (95% CI 5.4–8.1) with lapatinib plus capecitabine (HR 0.39 [95% CI 0.27–0.56]; P<0.0001), which met the criterion for statistical significance (≤0.0066). Among trastuzumab-resistant pts, prolonged PFS with pyrotinib plus capecitabine was also observed (12.5 months [95% CI 6.9 to not reached] vs 6.9 months [95% CI 5.4 to not reached]; HR 0.60 [95% CI 0.29 to 1.21]). Benefits in objective response rate, clinical benefit rate, and duration of response with pyrotinib plus capecitabine were also indicated (Table). The most common grade ≥3 adverse events were diarrhea (30.6% vs 8.3% in the pyrotinib vs lapatinib arm) and hand-foot syndrome (16.4% vs 15.2%). Conclusions: In pts with HER2+ MBC after trastuzumab and chemo, pyrotinib plus capecitabine achieved a significant better PFS than lapatinib plus capecitabine, with manageable toxicity, verifying the phase 2 findings. Clinical trial information: NCT03080805 . [Table: see text]
Surgery for unresectable stage IIIC and IV melanoma in the era of new systemic therapy.
Authors: Blankenstein Stephanie , Aarts Maureen J.B. , van den Berkmortel Franchette , Boers-Sonderen Marye , van den Eertwegh Alfonsus Johannes Maria , Franken Margreet G. , de Groot Jan Willem , Haanen John B. A. G. , Hospers Geke , Kapiteijn Ellen , Piersma Djura , Van Rijn Rozemarijn , Suijkerbuijk Karijn , ten Tije Albert J. , Van Der Veldt Astrid Aplonia Maria , Vreugdenhil Gerard , Wouters Michel W.J.M. , Van Akkooi Alexander Christopher Jonathan 
Published: May 2020

10032 Background: Over the past decade opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapies. However, selecting patients who will benefit from surgery after systemic therapy is still difficult. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage III and IV melanoma, who have previously been treated with immune checkpoint inhibitors (ICI) or targeted therapy, to provide insight in which patients may benefit from surgery. Methods: Data was extracted from the prospectively collected, nationwide, Dutch Melanoma Treatment Registry (DMTR) onunresectable stage IIIC or advanced/metastatic stage IV melanomapatients who obtained disease control with systemic therapy and underwent subsequent surgery. Disease control was defined as a complete response (CR), partial response (PR) or stable disease (SD). After disease control was achieved with systemic therapy, progressive disease (PD) was allowed as a most recent status of disease prior to surgery, to avoid excluding patients with oligoprogression. Major exclusion criteria were non-cutaneous melanoma and brain metastases. Results: Of 3959 patients in the DMTR database, 154 patients met our inclusion criteria. Of these patients, 79 (51%) were treated with ICI, 61 (40%) with targeted therapy and 9.1% with study or other treatments before surgery. The best response to systemic therapy was a CR in 5.2%, PR in 46.1% and SD in 44.2% of patients. At a median follow-up of 10.0 months (IQR 4-22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression free survival (PFS) was 9.0 months (95% CI 6.3-11.7). A multivariate cox regression analysis showed that when surgery led to CR or PR, the PFS and OS were better than if surgery led to SD or PD (p < 001). Also, ICI seemed to be more favorable than targeted therapy in both PFS (median of 15 versus 7 months) and OS (median not reached versus 32 months) (p = 0.026 and p = 0.003). Conclusions: We conclude that selected unresectable stage IIIC or stage IV melanoma patients might benefit from surgery after achieving disease control with systemic therapy. Expected residual tumor after surgery could be an important selection criterion. Especially patients undergoing surgery after initial tumor response on ICI have a chance of long-term survival.
A phase II study of ERK inhibition by ulixertinib (BVD-523) in metastatic uveal melanoma.
Authors: Buchbinder Elizabeth Iannotti , Cohen Justine Vanessa , Haq Rizwan , Hodi F. Stephen , Lawrence Donald P. , Giobbie-Hurder Anita , Knoerzer Deb , Sullivan Ryan J. 
Published: May 2020

10036 Background: Uveal melanoma is a rare and aggressive subset of melanoma that is minimally responsive to traditional therapies. Greater than 80% of uveal melanomas have a mutation in GNAQ or GNA11 which lead to downstream signaling through the MAPK pathway. This has led to efforts to treat uveal melanoma with MEK inhibition with mixed results. Ulixertinib (BVD-523) is a potent and reversible small molecule ATP-competitive inhibitor of both ERK1 and ERK2 protein kinases which has undergone phase I testing. Methods: We performed a phase II study to determine the efficacy and safety of BVD-523 in patients with metastatic uveal melanoma. This was conducted as a Simon two-stage design with a total sample size of 25 patients (pts) and an initial evaluation of efficacy after 13 pts. Two responses were required to continue to the second stage. Results: From April 2018 to April 2019 thirteen pts were enrolled. Pts were predominantly female (69%) with a median age of 64 yrs. (34 -76). Sites of metastasis included liver (84.6%) and lung (30.8%). Grade 3 and 4 toxicities associated with therapy were consistent with BVD-523 and other ERK inhibitors and included LFT elevation, hyponatremia, pruritis, amylase elevation, anemia and rash. The best response, per RECIST 1.1, was stable disease (SD) in 4 pts, and disease progression (PD) in 7 patients. Two patients were unevaluable for response due to withdrawing themselves from the study. Median time to progression was 2.0 months (90% CI: 1.8 – 3.6 mos.). There were eight deaths due to disease progression with a median survival time of 6.9 months (90%CI: 3.2 to 8.3 mos.). Analysis of correlative data from pre- and on-treatment biopsies exploring the change in expression of key signaling proteins relating to treatment is underway. Conclusions: ERK inhibition with ulixertinib (BVD-523) did not demonstrate activity in patients with metastatic uveal melanoma. The toxicities observed on study were consistent with what would be expected with MAPK pathway inhibition. Clinical trial information: NCT03417739.
Vismodegib (V) for organ preservation for locally advanced (LA) orbital/periocular basal cell carcinoma (BCC).
Authors: Worden Francis P. , Unsworth Shelby A , Andrews Chris A , Chan May , Bresler Scott , Bichakjian Christopher Keram , Durham Alison Bates , Demirci Hakan , Elner Victor , Nelson Christine , Kim Denise , Joseph Shannon , Swiecicki Paul , Kahana Alon 
Published: May 2020

10069 Background: LA BCC of the eye/lacrimal drainage system most often requires disfiguring radical surgery, possibly including exenteration. As an alternative to radical surgery, we evaluated ophthalmologic outcomes following treatment with V using a novel Visual Assessment Weighted Score (VAWS) in patients (pts) with locally advanced periocular BCC. Methods: In this open label, non-randomized trial, pts with globe- and lacrimal-threatening orbital/periocular BCC were scored with VAWS prior to treatment with 150 mg of V daily. Pts were evaluated by ophthalmic exam (OE) every 3 mo & with MRI/CT at 5-9 mo. Pts with progressive disease (PD) were offered salvage surgery. Tumor response was assessed by RECIST v1.1. Responders (CR, PR, SD) continued V if tolerating therapy. Pts with intolerable side effects stopped V & were offered surgery of their residual tumor. Post-surgical specimens were assessed for histologic presence of BCC by a dermatopathologist. The primary endpoint, maintenance of visual function, was evaluated by VAWS at final post treatment assessment (FPTA), 1 yr after the start of V or 2 mo post-surgery. A VAWS of 21/50 was considered successful, representing preservation of a functional eye. Results: 50 pts were planned for enrollment, but the study was stopped early for benefit. From 06/25/2015 to 05/16/2019, 35 pts signed consent; 1 was a screen failure; 34 (97%) received V & 35 were evaluable for analysis by ITT; 1 died from aspiration pneumonia. The median time on study was 261 days. Average treatment with V was 223 days. 32 (91%) underwent OE & 27 (77%) had an MRI/CT. 27 (77%) underwent surgery & 33 (94%) attained organ preservation. Overall response rate (ORR) on OE was 84% (0%-PD,6%-SD,29%-PR,54%-CR, 11% not assessed(NA)). ORR by MRI/CT was 72% (0%-PD,6%-SD, 26%-PR,46%-CR,22% NA). 31 (89%) were scored with VAWS at 3 mo & 30 (86%) at FPTA. The mean VAWS at baseline was 44/50, 46/50 at 3 mo, & 47/50 at FPTA. Of the 35 pts scored at baseline by VAWS, 1 (3%) had a major decline during follow up, 5 (14%) a minor decline, 27 (77%) stable/improved, & 2 (6%) NA. No pts experienced grade 3-5 events. Of the 27 post-surgical pathologic specimens evaluated for histological response, 67% had NED, 22% had clear margins, & 11% had BCC to the margin. Two pts have recurred & underwent Mohs surgery. Conclusions: Treatment with V led to organ preservation for pts with LA periocular BCC, with preservation of visual function. Vismodegib is practice changing as neoadjuvant therapy for LA BCC of the eye/lacrimal drainage system in which surgery would result in unacceptable morbidity. Clinical trial information: NCT02436408.
Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.
Authors: Khan Shaheer , Lutzky Jose , Shoushtari Alexander Noor , Jeter Joanne M. , Chiuzan Cody , Sender Naomi , Blumberg Lauren Esther , Nesson Alexandra , Singh-Kandah Shahnaz V. , Hernandez Susana , Ambrosini Grazia , Surriga Oliver , Schwartz Gary K. , Carvajal Richard D. 
Published: May 2020

10075 Background: Uveal melanomas (UM) measuring at least 12mm in base diameter with a class 2 signature as defined by gene expression profiling (DecisionDx-UM) are characterized by high metastatic risk, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk. The growth factor receptor Met is highly expressed in UM. We have previously shown that crizotinib, an inhibitor of Met, is an effective adjuvant therapy in preclinical models (Surriga et al, Mol Cancer Ther 2013). We therefore conducted a phase II study of adjuvant crizotinib in high-risk UM. Methods: Eligibility included: primary lesion ≥12mm in base diameter; class 2 by DecisionDx-UM testing; definitive therapy within 120 days before starting crizotinib; and, no evidence of metastatic disease. Patients (pts) received 12 four-week cycles of crizotinib (250 mg twice daily). Surveillance imaging (chest CT and MRI abdomen/pelvis) were performed q3 months. The primary endpoint was distant relapse-free survival (RFS). Secondary endpoints were overall survival (OS) and toxicity. We hypothesized that the addition of crizotinib would increase the 32 month RFS from 50% to 75% (α = 0.05; β = 0.11). Results: As of 1/31/2020, 34 pts had enrolled and received at least one dose of study drug with median age of 60 (range, 26-86); 41% female; and median ECOG PS 0 (range, 0-1). 2 pts could not be evaluated for the primary endpoint due to early withdrawal and loss to follow-up. The median time from primary treatment to crizotinib initiation was 60 days (range, 0-106). All pts experienced a treatment-related adverse event (AE) of any grade. 11/34 (32%) experienced a grade 3 or 4 AE, the most common being transaminase elevation (n = 8/11). 9 pts (28%) did not complete the full 48-week treatment course due to disease recurrence (n = 5) or toxicity (n = 4). An additional 5 pts required dose reduction due to hepatic toxicity or diarrhea. 15/32 evaluable pts developed distant disease relapse, with 14 developing relapse within 32 months. With a median duration of follow up of 28.7 months, the median RFS was 30.6 months (95% CI: 27.8-58.5%). The median OS was not reached. Conclusions: The use of adjuvant crizotinib in patients with high-risk UM did not reduce rates of relapse in this multicenter, single arm trial. 9/32 (28%) pts required dose modification or discontinuation due to AE which may have limited efficacy. Further investigations of adjuvant treatment options are warranted. Clinical trial information: NCT02223819.
Randomized trial of a collaborative palliative and oncology care intervention to improve communication about end-of-life care in patients with metastatic breast cancer.
Authors: Temel Jennifer S. , Moy Beverly , El-Jawahri Areej , Jackson Vicki A. , Kamdar Mihir , Jacobsen Juliet , Lindvall Charlotta , Shin Jennifer Adrienne , Rinaldi Simone , Carlson Heather , Sousa Angela , Gallagher Emily J. , Moran Samantha , Ruddy Margaret , Anand Maya , Carp Julia , Greer Joseph A. 
Published: May 2020

1008 Background: Studies have demonstrated the benefits of early, integrated palliative care in improving quality of life (QOL) and end-of-life (EOL) care for patients with poor prognosis cancers. However, the optimal timing and outcomes of delivering palliative care for those with advanced cancers that have longer disease trajectories, such as metastatic breast cancer (MBC), remains unknown. We tested the effect of a collaborative palliative and oncology care model on communication about EOL care in patients with MBC. Methods: Patients with MBC and clinical indicators of poor prognosis (N=120) were randomized to receive collaborative palliative and oncology care or usual care between 05/02/2016 and 12/26/2018. The intervention entailed five structured palliative care visits, including a joint visit with oncology when possible, which focused on symptom management, coping, prognostic awareness, decision-making, and planning for EOL. The primary outcome was documentation of EOL care discussions in the electronic health record. Patients also completed questionnaires at baseline and 6, 12, 18, and 24 weeks regarding communication with clinicians about EOL care, QOL, and mood symptoms. Results: The sample included only women (100.0%) who mostly identified as white (87.5%), with a mean age of 56.91 years (SD=11.24). The rate of EOL care discussions documented in the health record was higher among intervention patients versus those receiving usual care (67.2% vs 40.7%, p=0.006), including a higher completion rate of a Medical Orders for Life Sustaining Treatment form (39.3% vs 13.6%, p=0.002). Intervention patients were also more likely to report discussing their EOL care wishes with their doctor compared to usual care patients (OR=3.10, 95% CI: 1.21, 7.94, p=0.019). Study groups did not differ in reported QOL or mood symptoms. Conclusions: This novel collaborative palliative care intervention significantly improved communication and documentation regarding EOL care for women with MBC. Further work is needed to examine the effect of this care model on healthcare utilization at the end of life.