bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sentinel-Lymphnode Biopsy in primary breast cancer: 99mTc versus ICG—A prospective, randomized trial.
Authors: Kern Peter , Bittner Ann-Kathrin , Hoffmann Oliver , Kimmig Rainer , Schoffer Ariane , Moukas Stephanos , Friedrichs Kay 
Published: May 2020

575 Background: Sentinel-Lymphnode Biopsy (SLNB) is the standard procedure in primary breast cancer, routinely performed with 99mTechnetium radioactive tracers. Awareness of nuclear waste, costs and time consumption lead to the desire of breast surgeons to find safe and effective alternative options for detection of sentinel lymph nodes (SLN) in breast cancer and melanoma. Indocyaningreen is a tracer which emits fluorescence with near-infrared light of 780-810 nm when injected in the peritumoral or periareolar region, enabling surgeons to detect SLN and lymphatic pathways at the breast. Methods: We performed a prospective, randomized trial with patients with primary breast cancer. Both detection methods have been applied to patients of the study cohort comparing the preparation time, time to identify, concordance of the two methods and costs. Reference method was preoperative lymphszintigraphy. Results: 55 patients have been analyzed in this first report. Preparation time was 75,8 min (range 60-120 min) for 99mTc-tracer and a standard of 20 min for ICG. Time to identify SLN at a mean of 3,8 min(range 1-15 min) for 99mTc and 3 min (range 1-8 min) for ICG. Concordance rates were 98,2 % for the 1st SLN, 93,8 % both for 2nd and 3rd SLN. After neoadjuvant chemotherapy, all SLN have been been detected by both techniques, in 3 patients additional SLN have been found by ICG. Costs have been cut down to 1/10 with the use of ICG, coming up to saving of 27 000 US-$ per each 100 SLNB procedures performed. Conclusions: We report a high concordance rate between the 2 techniques - 99mTechnetium and ICG with near-infrared - for detection of SLN in breast cancer. Preparation time is cut down to less than 30 %, and costs to less the 10 % of radioactive labelling. Clinical trial information: 18-8054-BO .
Re-excision rates among older breast cancer patients undergoing breast-conserving surgery (BCS): Impact of the SSO-ASTRO consensus guideline on margins.
Authors: Chavez-MacGregor Mariana , Lei Xiudong , Tamirisa Nina , Caudle Abigail Suzanne , Giordano Sharon H. 
Published: May 2020

576 Background: BCS has been historically associated with a high re-excision rate, driven in part by the need of obtaining negative margins. The SSO-ASTRO consensus guideline on invasive margins, defined a negative margin as no ink on tumor. In this large population-based study of older breast cancer patients undergoing BCS for invasive breast cancer we evaluate the guideline impact on re-excision rates. Methods: Female patients diagnosed with stage I-II breast cancer between 2012-2015 were identified in the SEER-Medicare database. Patients were >66 years and underwent BCS. Patients treated with neoadjuvant chemotherapy were excluded. We defined the following time periods: pre-guideline (January 2012-September 2013); peri-guideline (October 2013-March 2014) and post-guideline (April 2014-December 2016). Re-excision was defined as a resection, BCS or mastectomy identified using ICD-9 or CPT codes between 4 and 90 days after initial BCS. Overall re-excision rates and 95%CI were calculated and groups compared using X2test. Within subgroups we calculated re-excision rates for the pre and post-guideline periods and report the relative percent change. Regression model evaluated the association between time periods and re-excision while adjusting for important covariates, risk ratios (RRs) and 95%CI are presented. Results: 17001 patients were included. 6762 of them had BCS in the pre, 1786 in the peri, and 8453 in the post-guideline periods. Overall 22.6% of the patients had a re-excision. The rate decreased from 24.8% pre-guideline to 20.3% post-guideline (P < 0.001). The relative change in re-excision varied according to region (Midwest 3-7.3%, Northeast -20%, West -16.5% and South -13.5%) Differences in the relative change according to race/ethnicity were also seen (Whites -19.2, Blacks -15.3% and Hispanics -9.9%). In the multivariable model, BCS in the post-guideline period was associated with a decreased risk of re-excision (RR = 0.83; 95%CI 0.79-0.88). Lobular histology was associated with a higher risk of re-excision (RR = 1.31; 95%CI 1.21-1.42); greater surgeon volume was associated with lower risk of re-excision (RR = 0.89; 95%CI 0.82-0.95). Conclusions: There has been a statistically significant decrease in the re-excision rate after BCS associated with the dissemination of the SSO-ASTRO consensus guideline on invasive margins. Our study confirms the impact that guidelines have modifying patterns or practice, reducing the frequency of unnecessary interventions.
Four-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer in neoadjuvant setting.
Authors: Pivot Xavier , Pegram Mark D. , Cortes Javier , Lüftner Diana , Rugo Hope S. , Lyman Gary H. , Curigliano Giuseppe , Bondarenko Igor , Dvorkin Mikhail , Yoon Ye Chan , Kim Younsoo , Kim Chul 
Published: May 2020

578 Background: SB3 was approved in the US and EU as a biosimilar of reference trastuzumab (TRZ). Here, we report 4-year cardiac safety and survival outcomes. Methods: After completing neoadjuvant-adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study of a phase III trial (Pivot et al. Eur J Cancer 2019). The aim was to observe long-term cardiac safety and survival. EFS and OS were analyzed in subgroups by ADCC status within TRZ in ad-hoc analyses. Results: Of 875 patients randomized in the phase III trial, 367 patients (SB3, N=186; TRZ, N=181) were enrolled in the follow-up study. The median follow-up was 53 months. During the follow-up, the incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease was low (SB3, n=1; TRZ, n=2), with all patients recovering with LVEF ≥ 50%. No cases of symptomatic congestive heart failure, cardiac death, or other significant cardiac condition were reported. 4-year EFS rates were 83.4% for SB3 and 80.7% for TRZ with a HR of 0.77 [95% CI 0.47, 1.27]. 4-year OS rates were 94.3% for SB3 and 89.6% for TRZ with a HR of 0.53 [95% CI 0.24, 1.16]. From ad-hoc analysis, a difference in EFS and OS was seen between Non-drifted TRZ and Drifted TRZ; Difference between SB3 and Non-drifted TRZ was not statistically significant. Conclusions: In a subset of patients from the phase III trial, comparable long-term cardiac safety and survival at 4-year supports biosimilarity between SB3 and TRZ. Ad-hoc analysis results by ADCC status suggest a possible correlation between ADCC and clinical efficacy. Further follow-up is needed. Clinical trial information: NCT02771795 . [Table: see text]
Survival analysis of the prospective randomized Cher-Lob study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer (BC).
Authors: Guarneri Valentina , Dieci Maria Vittoria , Bisagni Giancarlo , Generali Daniele Giulio , Cagossi Katia , Sarti Samanta , Frassoldati Antonio , Gianni Lorenzo , Cavanna Luigi , Pinotti Graziella , Musolino Antonino , Piacentini Federico , Michelotti Andrea , Cinieri Saverio , Griguolo Gaia , Miglietta Federica , De Salvo Gian Luca , Conte Pier Franco 
Published: May 2020

582 Background: The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here we report the results of survival analysis according to treatment arm and pCR. Methods: The CherLOB study randomized 121 HER2-positive, stage II-IIIA breast cancer patients to anthracyclines/taxane-based chemotherapy plus trastuzumab, lapatinib, or both. After surgery, patients received adjuvant trastuzumab for up to 1 year. The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib (Guarneri, J Clin Oncol 2012). Relapse-free survival (RFS) was calculated from randomization to breast cancer recurrence (locoregional or distant) or death from any cause, whichever first. Overall survival (OS) was calculated from randomization to death from any cause. Results: At a median follow up of 8.8 years, RFS rates at 5 years were: 85.8% in the trastuzumab + lapatinib arm, 77.8% in the trastuzumab arm, 78.1% in the lapatinib arm (log-rank p = 0.160). Patients treated with dual HER2 blockade (trastuzumab + lapatinib arm) experienced numerically better RFS as compared to patients treated with single HER2 blockade (trastuzumab arm and lapatinib arm combined): 5-yr RFS 85.8% vs 78.0%, log-rank p = 0.087; HR = 0.51, 95% CI 0.23-1.12, p = 0.093. The achievement of pCR was a strong prognostic factor. 5-yr RFS rate was 97.3% for pCR patients vs 72.9% for non-pCR patients (log-rank p < 0.001, HR = 0.12, 95% CI 0.03-0.49, p = 0.003); similar significant results were observed in both the estrogen receptor-negative and estrogen-receptor positive subgroups. OS was also improved in pCR patients: 8-yr OS rates were 97.2% vs 80.0% for non pCR patients (log-rank p = 0.028, HR = 0.14, 95% CI 0.02-1.08, p = 0.060). Conclusions: In the Cher-LOB study, there was a not statistically significant signal for a better RFS for patients who received dual HER2 blockade with trastuzumab and lapatinib plus chemotherapy as compared to patients treated with single anti-HER2 agent (trastuzumab or lapatinib) plus chemotherapy. Patients achieving a pCR had longer RFS and OS as compared to non-pCR patients. Clinical trial information: NCT00429299 .
Statistical modeling of a novel clinical trial design using neoadjuvant therapy (NAT) to personalize therapy in patients (pts) with triple-negative breast cancer (TNBC).
Authors: Moulder Stacy L. , Bassett Roland L. , White Jason B , Huo Lei , Damodaran Senthil , Lim Bora , Ueno Naoto T. , Murthy Rashmi Krishna , Arun Banu , Valero Vicente , Tripathy Debu , Hortobagyi Gabriel N. , Litton Jennifer Keating , Thompson Alastair Mark , Mittendorf Elizabeth A. , Ravenberg Elizabeth , Santiago Lumarie , Adrada Beatriz E , Candelaria Rosalind P , Rauch Gaiane M 
Published: May 2020

595 Background: 40-50% of pts with TNBC develop pathologic complete response (pCR) with adriamycin/cyclophosphamide (AC)àtaxane (T) NAT; thus, most pts treated in randomized trials (RCTs) adding experimental drugs (ED) to standard NAT do not benefit from trial participation. A personalized trial design that enriches for non-pCR to standard NAT would diminish toxicity from ED in pts who do not need them and enrich ED in high-risk pts that are most likely to benefit. Methods: ARTEMIS (NCT02276443) is a non-randomized trial to study personalization of NAT in TNBC. Tumor biopsies were performed pre-NAT and volumetric change by ultrasound (VCU) after 4 cycles of AC (or upon clinical progression) assessed response. Pts with sensitive TNBC (VCU >=70% after AC) had T as the second phase of NAT. Pts with <70% VCU were offered phase II trials. pCR was assessed at surgical resection. 273 pts had available pCR status and 222 had complete data to generate a model predictive of response using multivariate logistic regression with common clinical factors. Data was randomly divided into training (n=111) and validation (n=111) sets. Results: 85 pts (38%) had pCR and VCU after AC x 4 was the strongest predictor of pCR. Other factors significant on multivariate analysis and included in the model were T stage (T1-4), stromal TIL, Ki67 and PD-L1. When applied to the validation data set, the accuracy of this model for predicting pCR was 76.6%, sensitivity 78.6% and specificity 75.4%. The PPV was 66.0% and the NPV was 85.2% with a ROC curve AUC of 82.4%. Using these data, ED exposure (table) was estimated for the ARTEMIS study design vs a 1:1 or a 2:1 RCT design (with an estimated pCR in control arm=40%), with a demonstrated benefit for personalization. Conclusions: This modeling indicates that personalization of NAT trials has the potential to enrich ED exposure for non-responsive disease as well as diminish ED exposure in pts likely to achieve pCR with standard NAT. Improved prediction of pCR would further enhance personalized trial design. Clinical trial information: NCT02276443 . [Table: see text]
A randomized phase III trial of secondary cytoreductive surgery in later recurrent ovarian cancer: SOC1/SGOG-OV2.
Authors: Zang Rongyu , Zhu Jianqing , Shi Tingyan , Liu Jihong , Tu Dongsheng , Yin Sheng , Jiang Rong , Zhang Ping , Jia Huixun , Luan Yuting , Zhang Yuqin , Chen Xiaojun , Huang Xiao , Tian Wenjuan , Gao Wen , Feng Yanling , Yang Huijuan , Cheng Xi , Cai Yulang ,   Shanghai Gynecologic Oncology Group
Published: May 2020

6001 Background: In China, secondary cytoreductive surgery (SCR) has been standard of care in some high volume cancer centers for ovarian cancer (OC) and most pts prefer surgery over the past two decades. Although GOG213 showed no OS benefit, the debate on selected pts and the conflict with certain local clinical care is still open. Methods: Pts with 1st relapsed OC after 6m+ platinum-free interval (PFI) were eligible if predicted to be a potential R0 by iMODEL score combined with PET-CT image and were randomized to SCR followed by chemotherapy (surgery arm) vs 2nd line chemotherapy alone (no surgery arm). Co-primary endpoint is PFS and OS. The 2nd endpoint is accumulated treatment-free survival (TFSa), which was defined as the overall survival time minus the time of surgery and chemotherapy after randomization. We report analysis of PFS and interim analysis of TFSa. Results: 357 pts were randomized 2012-2019. 6.3% of 175 pts were operated in no surgery arm and cross-over rate was 36.9% in 2nd+ relapsed pts of no surgery arm. 97% and 96% of pts received a platinum-containing 2nd line therapy. Complete resection (R0) rate was 76.7% in overall and 61.1% in pts with iMODEL> 4.7. 60 d mortality rates were 0 % in both surgery and no surgery arm. Postoperative 30 d complication rate with ≥ grade 3 was 5.2%. The median follow-up was 36.0 m. Median PFS was 17.4 m and 11.9 m in surgery and no surgery arm, respectively (HR 0.58, 95% CI 0.45-0.74, p < 0.001). Median time to start of first subsequent therapy (TFST) was 18.1 m vs 13.6 m in favor of the surgery arm (HR 0.59, 95%CI 0.46-0.76). 1.1% and 10.1% of pts underwent Bevacizumab and PARPi maintenance in the 2nd line therapy. The OS and TFSa was immatured. The median TFSa was unreached and 39.5 m in R0 subgroup and no surgery arm, respectively (HR0.59, 95%CI 0.38-0.91). TFSa in surgery arm showed a better long-term survival than that in no surgery group (restricted mean survival time from 60 to 72m: 6.2m vs 4.2m). Conclusions: SCR in selected pts resulted in a dramatically significant extension of PFS. The interim analysis of TFSa indicate that SCR might contribute to long-term survival.
Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation.
Authors: Poveda Andres , Floquet Anne , Ledermann Jonathan A. , Asher Rebecca , Penson Richard T. , Oza Amit M. , Korach Jacob , Huzarski Tomasz , Pignata Sandro , Friedlander Michael , Baldoni Alessandra , Park-Simon Tjoung-Won , Sonke Gabe S. , Lisyanskaya Alla Sergeevna , Kim Jae-Hoon , Filho Elias Abdo , Vergote Ignace , Rowe Phil , Pujade-Lauraine Eric 
Published: May 2020

6002 Background: SOLO2 (ENGOT ov-21; NCT01874353) showed that maintenance therapy with the PARP inhibitor olaparib in pts with platinum-sensitive relapsed ovarian cancer (PSROC) and a BRCA mutation (BRCAm) led to a statistically significant improvement in median progression-free survival (PFS) of 13.6 months vs placebo (hazard ratio [HR] 0.30). Time to second progression or death significantly improved (Pujade-Lauraine et al Lancet Oncol 2017) and a quality-adjusted PFS benefit was seen (Friedlander et al Lancet Oncol 2018) with maintenance olaparib vs placebo. We report the preplanned final OS analysis for SOLO2. Methods: Pts with PSROC and a BRCAm who had received ≥2 lines of treatment and were in response to their most recent platinum-based chemotherapy received maintenance olaparib (300 mg bid tablets) or placebo. Pts were stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6–12 months vs >12 months). OS was a secondary endpoint. The only preplanned OS sensitivity analysis was an OS analysis in the Myriad germline BRCAm subset (Myriad BRAC Analysis test). Results: At final data cut-off (Feb 3, 2020), median follow-up was 65 months in both treatment arms. A long-term treatment benefit was seen with olaparib vs placebo with an OS HR of 0.74 (95% confidence interval [CI] 0.54–1.00) in the full analysis set (FAS; unadjusted for crossover; 38.4% of placebo pts crossed over to a PARP inhibitor) (Table). At 5 years: by Kaplan-Meier estimates, 28.3% of pts in the olaparib arm vs 12.8% of pts in the placebo arm were alive and had still not received subsequent treatment; 42.1% of olaparib pts vs 33.2% of placebo pts were alive. The long-term tolerability profile of olaparib was generally consistent with that reported previously. Conclusions: In the final analysis of SOLO2, maintenance olaparib provided an unprecedented improvement of 12.9 months in median OS vs placebo. This is the first study with olaparib tablets, and the first since Study 19 (NCT00753545), to provide long-term follow-up and final OS data in pts with PSROC and a BRCAm. Clinical trial information: NCT01874353. [Table: see text]
A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer.
Authors: Liu Joyce F. , Brady Mark F. , Matulonis Ursula A. , Miller Austin , Kohn Elise C. , Swisher Elizabeth M. , Tew William P. , Cloven Noelle Gillette , Muller Carolyn , Bender David , Moore Richard G. , Michelin David Paul , Waggoner Steven E. , Geller Melissa Ann , Fujiwara Keiichi , D'Andre Stacy D. , Carney Michael , Secord Angeles Alvarez , Moxley Katherine M. , Bookman Michael A. 
Published: May 2020

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O, or O alone, was superior to standard of care (SOC) plat-based therapy in relapsed plat-sensitive ovca. Methods: Eligible pts had recurrent plat-sensitive [ > 6-month plat-free interval (PFI)] high-grade serous or endometrioid, or BRCA-related, ovca. One prior non-plat therapy and unlimited prior plat-therapies were allowed; prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were exclusions. Pts were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily). Randomization was stratified by g BRCA status, PFI (6-12 vs > 12 months), and prior anti-angiogenic therapy. Target sample size was 549 pts; primary analysis occurred 2 years after the last pt enrolled. The primary endpoint was PFS. Type 1 error = 0.025 was controlled by a gatekeeping hierarchy that assessed C+O vs SOC, then O alone vs SOC, and finally C+O vs O. All maintenance therapy was prohibited. Results: Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had g BRCAmut. Median follow-up was 29.1 months. 53 pts on SOC initiated non-protocol therapy (predominantly PARP inhibitor maintenance) before disease progression. The hazard ratio (HR) for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) between C+O and SOC and 1.20 (95% CI 0.93-1.54) between O and SOC, with median PFS of 10.3, 8.2, and 10.4 months for SOC, O, and C+O, respectively. Response rates were 71.3% (SOC), 52.4% (O), and 69.4% (C+O). In gBRCA pts, HR for PFS was 0.55 (95% CI 0.73-1.30) for C+O vs SOC, and 0.63 (95% CI 0.37-1.07) for O vs SOC. In non-g BRCA pts, HR for these comparisons was 0.97 (95% CI 0.73-1.30) and 1.41 (1.07-1.86). No OS differences between arms were observed at 44% events. Pts receiving C+O (vs SOC) had more frequent Grade 3 or higher gastrointestinal (30.1% vs 8.4%), hypertension (31.7% vs 1.8%), and fatigue events (17.5% vs 1.8%). Conclusion: C+O demonstrated similar activity to SOC in relapsed plat-sensitive ovca but did not meet the primary endpoint of improved PFS. Clinical trial information: NCT02446600.
Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer.
Authors: Gilbert Lucy , Oaknin Ana , Matulonis Ursula A. , Mantia-Smaldone Gina , Lim Peter C , Castro Cesar Martin , Provencher Diane M. , Memarzadeh Sanaz , Wang Jiuzhou , Esteves Brooke , Zweidler-McKay Patrick A , Moore Kathleen N. , O'Malley David M. 
Published: May 2020

6004 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥ 50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PR) (recurrence within 6 months after last platinum dose) or platinum sensitive (PS) responded to the last platinum therapy received before study entry and did not progress within 6 months) disease for whom a non-platinum based doublet would be appropriate. Methods: Pts received MIRV (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed by investigator according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 60 pts received the combination, with a median age of 60 years, and a median of 2 prior lines of systemic therapy (range 1-4). Platinum status was determined for 56 pts, with 30 (50%) considered PR and 26 (43%) considered PS; platinum status data were incomplete for 4 pts. The most common treatment related AEs (percent all grade/grade 3+) were diarrhea (65/2), blurred vision (62/3), nausea (55/0), and fatigue (55/5). The most common treatment related grade 3+ AEs were hypertension and neutropenia, (10% each); all other grade 3+ events occurred in ≤ 5% of pts. Serious AEs regardless of relationship to study drug were infrequent, with the most common events being small intestinal obstruction in 3 pts, 5% (grade 3) and pneumonitis in 3 pts, 5% (2 grade 1; 1 grade 2). Objective responses were seen in 26 pts for a confirmed overall response rate (ORR) of 43% (95% CI, 31, 57). In a subset analysis of pts with high FRα expressing tumors (n = 33), the confirmed ORR was 61% (95% CI, 42, 77), with an ORR of at least 50% in each of the PR and PS subsets. With a median follow-up of 5.5 months, the duration of response and progression free survival data are immature. Conclusions: The combination of MIRV with BEV demonstrates an encouraging ORR with a favorable tolerability profile in pts with recurrent ovarian cancer regardless of platinum sensitivity, particularly in those with tumors that express high levels of FRα. Clinical trial information: NCT02606305.