Soluble PD-L1 as a marker of progressive disease on nivolumab in kidney cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 746-746
Author(s):  
Kathleen Margaret Mahoney ◽  
Petra B. Ross-Macdonald ◽  
Sachet A. Shukla ◽  
David A. Braun ◽  
Linan Song ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Progressive Disease ◽  
Tumor Tissue ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Tumor Specimen ◽  
Wilcoxon Rank Sum Test ◽  
Treatment Naïve

746 Background: Higher levels of soluble PD-L1 (sPD-L1) are associated with poor prognosis in patients with solid tumors including in renal cell carcinoma (RCC). Here we have tested whether in patients with advanced RCC, sPD-L1 levels are associated with PD-L1 expression on tumor tissue or with clinical outcomes on PD-1 blockade. Methods: Serum from 91 patients with advanced clear-cell RCC on a biomarker study of nivolumab (NCT01358721) obtained at baseline (Day 1), Day 29 and Day 63, was tested by SiMoa™ for sPD-L1 (capture mAb 298.12B1, detection mAb 339.4C10; Freeman laboratory and Quanterix). Tumor PD-L1 (tPD-L1) was assessed on pretreatment biopsies (Dako). Association of sPDL1 and tPD-L1 with clinical outcomes was analyzed, including best overall response by RECIST (BOR), objective response of >20% (OR), progression free survival (PFS), and overall survival (OS). Results quote Wilcoxon Rank Sum test or paired t-test with significance at P < 0.05. Results: Median sPD-L1 was highest in patients with progressive disease (PD) at all timepoints (Table). Compared to baseline, sPD-L1 levels significantly increased in patients with PD on Day 29 and Day 63, while sPD-L1 levels significantly decreased in patients with CR/PR on Day 63. In addition, we found significantly higher baseline sPD-L1 in patients with prior therapy compared to those who were treatment-naïve. High tPD-L1 was weakly associated with favorable OR, but also weakly associated with high baseline sPD-L1. Conclusions: Unlike tPD-L1, sPD-L1 levels may show promise for association with clinical response to nivolumab in RCC. In this exploratory study, sPD-L1 increase on-treatment was significantly associated with lack of OR, and may be of utility as an early marker for PD worthy of future validation. Analysis of RNASeq from patients’ tumor specimen is underway to assess whether high sPD-L1 with PD is associated with immune suppressive signatures.[Table: see text]

scholarly journals 177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

2021 ◽  
pp. 1167-1175
Author(s):  
Swayamjeet Satapathy ◽  
Bhagwant R. Mittal ◽  
Ashwani Sood ◽  
Apurva Sood ◽  
Rakesh Kapoor ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Octreotide Lar ◽  
Treatment Naïve ◽  
Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

scholarly journals Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy

2019 ◽  
Vol 15 (34) ◽  
pp. 3935-3944 ◽  
Author(s):  
Sarah S Mougalian ◽  
Bruce A Feinberg ◽  
Edward Wang ◽  
Karenza Alexis ◽  
Debanjana Chatterjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Eribulin Mesylate ◽  
Free Survival

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eriublin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

Expression patterns of gpNMB in breast cancer (BC): Retrospective evaluation of tumor tissue from the phase II EMERGE study.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 129-129
Author(s):  
Denise A. Yardley ◽  
Michelle E. Melisko ◽  
Andres Forero ◽  
Rebecca G. Bagley ◽  
Joshua Zhang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Tissue ◽  
Transmembrane Protein ◽  
Expression Patterns ◽  
Objective Response ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Free Survival ◽  
Disease Characteristics ◽  
Clinical Trial Information

129 Background: Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in ~20% of BC. gpNMB promoted BC metastases in a murine model and is a poor prognostic marker in BC patients (pts) (Rose 2010). Glembatumumab vedotin (GV, CDX-011) is a novel antibody-drug conjugate targeting gpNMB+ cancer cells with the potent cytotoxin monomethyl auristatin E. In a Phase I/II and in the Phase II EMERGE study, GV was well-tolerated (treatment-related toxicity included rash, neutropenia, and neuropathy) with promising activity in gpNMB+ BC tumors including TNBC. In EMERGE, GV vs. investigator’s choice chemotherapy, demonstrated an objective response rate of 30% (7/23) vs. 9% (1/11) in pts with tumor gpNMB overexpression (gpNMB in > 25% of tumor cells); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC. Improvements in progression-free survival (hazard ratio (HR) = 0.11) and overall survival (HR = 0.14) in gpNMB-overexpressing TNBC were noted. Methods: This retrospective analysis of the EMERGE study examined frequency of gpNMB overexpression by various baseline and disease characteristics. Tumors were centrally assessed by immunohistochemistry (IHC) and included data for 328 pts. Results: Tumor gpNMB overexpression was present in 21% (69/328) of screened and 40% (38/96) of TNBC pts. gpNMB overexpression was consistent in progesterone, estrogen, or HER2+ expressing tumors at rates of 12-15%. gpNMB overexpression was not observed among 17 lobular tumors, but was present in 21% (57/270) of ductal tumors. gpNMB overexpression was seen across organ sites, including lung (43%, 3/7), lymph node (31%, 12/39), chest wall (23%, 3/13), breast (21%, 44/209), bone (13%, 1/8), and liver (13%, 3/24). There were no apparent differences in gpNMB overexpression by age, race or disease setting (early vs. advanced) at tissue collection. Analysis is ongoing to determine if prior treatments may upregulate gpNMB expression. Conclusions: gpNMB overexpression in BC, especially in TNBC, appears consistent in archival primary and/or metastatic BC, regardless of age. A randomized multicenter study of GV in gpNMB overexpressing metastatic TNBC (METRIC) is ongoing. Clinical trial information: NCT01156753.

Outcomes of talazoparib (TALA) versus physician's choice of chemotherapy (PCT) in patients (pts) with advanced breast cancer (ABC) and a germline BRCA (gBRCA) mutation by line of chemotherapy (CT) in the EMBRACA trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1071-1071
Author(s):  
Johannes Ettl ◽  
Sara A. Hurvitz ◽  
Hope S. Rugo ◽  
Kyung-Hun Lee ◽  
Lida A. Mina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
The Us ◽  
Intent To Treat

1071 Background: The PARP inhibitor TALA was approved in the US for treatment of g BRCA-mutated ABC based in part on the EMBRACA study. Understanding the outcomes of EMBRACA pts relative to prior CT is a current unmet need. Methods: EMBRACA was a randomized Phase 3 trial comparing TALA 1 mg daily vs PCT (capecitabine, eribulin, gemcitabine, vinorelbine) in g BRCA-mutated ABC. Clinical outcomes were assessed by line of prior CT for ABC in intent-to-treat (ITT), triple-negative breast cancer (TNBC), and hormone receptor-positive (HR+) breast cancer cohorts. Results: 431 pts were randomized (ITT; TALA 287; PCT: 144). TALA was generally more effective than PCT across efficacy endpoints regardless of line of CT (Table). For the ITT population, TALA improved progression-free survival (PFS) and objective response rate (ORR) vs PCT for each line of CT assessed. Other prespecified subgroups (TNBC and HR+) will be presented. Conclusions: In pts with g BRCA-mutated ABC, TALA demonstrated improvements in clinical outcomes compared with PCT regardless of prior lines of CT. Clinical trial information: NCT01945775. [Table: see text]

Sites of metastasis (mets) and association with clinical outcomes (CO) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (cabo).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 585-585
Author(s):  
Dylan J Martini ◽  
Julie M. Shabto ◽  
Yuan Liu ◽  
Bradley Curtis Carthon ◽  
Alexandra Speak ◽  
...  
Keyword(s):  
Lymph Node ◽  
Clinical Outcomes ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Systemic Treatments

585 Background: Cabo is approved for the treatment for mRCC. We investigated the association of sites of mets and clinical outcomes (CO) in mRCC pts treated with cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016 to 2018. Overall survival (OS) and progression-free survival (PFS) were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. Objective response was defined as a complete response (CR) or partial response (PR). Sites of mets were obtained from radiology and clinic notes and included bone, lymph node, brain, lung, and liver. Univariate analysis (UVA) and multivariate analysis (MVA) was performed using Cox proportional hazard or logistic regression model. Results: The median age was 63 years and most (68%) were males. The majority of pts (79%) had ccRCC and 48% received at least 2 prior systemic treatments. The distribution of mets were: bone (42%), lymph node (69%), brain (6%), lung (83%), and liver (40%). The UVA and MVA of association between sites of mets and CO are presented in Table. Pts with bone mets had significantly longer OS in UVA and trended towards longer OS and PFS in MVA compared to pts without bone mets. Conclusions: Bone mets may be a prognostic factor for improved CO in mRCC pts treated with cabo. Larger studies are needed to validate the results of this study. UVA and MVA† of bone metastases and CO. [Table: see text]

Angiogenic and immunomodulatory biomarkers in axitinib-treated patients (pts) with advanced renal cell carcinoma (aRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 614-614 ◽  
Author(s):  
Brian I. Rini ◽  
Bernard Escudier ◽  
Danielle Murphy ◽  
Panpan Wang ◽  
Jamal Christo Tarazi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Outcomes ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Kaplan Meier ◽  
Clinical Trial Information

614 Background: Axitinib (axi) is approved for 2nd-line treatment of aRCC. In AXIS trial, median progression-free survival (PFS) was significantly longer in axi- vs sorafenib (sor)-treated pts (hazard ratio [HR] 0.67, 95% CI 0.54–0.81, P<0.0001). Association between mRNA/miRNA expression and clinical outcomes in a subset of axi- or sor-treated pts from AXIS was assessed. Methods: mRNA/miRNA analyses were performed on archival tumor samples. Expression was summarized for responders (complete and partial response) vs non-responders (stable and progressive disease), and for maximum percent tumor change. PFS and overall survival (OS) were analyzed by Kaplan-Meier. Results: Pt characteristics were similar between axi (n=34) and sor (n=33) arms. Association with outcomes is shown in the Table. A correlation was observed for CD68 protein and mRNA expression in axi-treated pts (R=0.4774 P=0.0043 and R=0.3985 P=0.0196, respectively). Both CXCR4 and TLR3 showed differences between treatment arms and association with PFS. TNFSF10 <median, and CD163, CSF1R and miR-221-5p ≥median were associated with shorter OS with axi vs sor ( P<0.05). Clinical trial information: NCT00678392. Conclusions: Immune-related biomarkers were associated with clinical outcomes in axi/sor-treated aRCC pts. Lower CCR7 expression was associated with better response and OS in axi-treated pts. CXCR4 and TLR3 may be predictive of response to axi. Analysis in a larger cohort is warranted.[Table: see text]

scholarly journals CTNI-53. SINGLE ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY OF THE RADIONUCLIDE 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii54-ii55
Author(s):  
Sylvia Kurz ◽  
Elcin Zan ◽  
Jasone Gurewitz ◽  
Christine Cordova ◽  
Andrea B Troxel ◽  
...  
Keyword(s):  
Treatment Response ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Somatostatin Receptor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Intracranial Meningiomas ◽  
Promising Treatment

Abstract BACKGROUND Meningiomas are the most common primary intracranial neoplasm. Once surgical and radiotherapeutic options are exhausted, there are no effective medical treatments available. A majority of meningiomas express somatostatin receptor 2 (SSTR2), representing a promising treatment target. 177Lu-DOTATATE is a SSTR2-targeting radionuclide that has been successful in SSTR2-expressing neuroendocrine tumors. Here we hypothesize that 177Lu-DOTATATE is effective in treating progressive intracranial meningiomas. METHODS In this ongoing phase II study (NCT03971461), adults with advanced intracranial meningiomas received 177Lu-DOTATATE 7.4 GBq (200 mCi) every 8 weeks for 4 doses. 68Ga-DOTATATE PET-MRI was obtained before and at the end of treatment (EOT). The primary endpoint was progression-free survival at 6 months (PFS-6). Correlative studies evaluated the association of PFS-6, objective response rate, progression-free survival, overall survival with radiographic tumor measurements, 68Ga-DOTATATE uptake on PET-MRI, SSTR2 expression in tumor, and meningioma methylation subclass. RESULTS Nine patients (F = 7, M = 2) with progressive meningiomas (WHO I = 2, II = 6, III = 1) have been enrolled. Median age was 63 (range 49–78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated, although CTCAE grade 3/4 electrolyte derangements and cytopenias were observed. Six patients reached PFS-6, three patients experienced progressive disease. Four patients had EOT 68Ga-DOTATATE PET-MRI evaluations in which anatomic measurements and 68Ga-DOTATATE standardized uptake values (SUV) pre- and post-treatment were assessed: one patient had reduced SUV measurements in all target lesions indicating altered SSTR2 expression and functional treatment response, one patient had stable disease, one patient had a mixed treatment response, and one patient experienced progressive disease. CONCLUSIONS SSTR2-targeting 177Lu-DOTATATE represents a promising treatment option for patients with progressive intracranial meningiomas. Treatment is well tolerated and can lead to functional alteration of tumoral SSTR2 expression by 68Ga-DOTATATE PET-MR imaging.

Association of neutrophil to lymphocyte ratio (NLR) with efficacy from JAVELIN Renal 101.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Mehmet Asim Bilen ◽  
Brian I. Rini ◽  
Robert J. Motzer ◽  
James M. G. Larkin ◽  
John B. A. G. Haanen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Continuous Variable ◽  
Phase 3 ◽  
Free Survival ◽  
Recist 1.1 ◽  
Treatment Naïve ◽  
Clinical Trial Information

5061 Background: The phase 3 JAVELIN Renal 101 trial (NCT02684006) in treatment-naive patients with advanced renal cell carcinoma (aRCC) demonstrated significantly improved progression-free survival (PFS; hazard ratio [HR], 0.69; 95% CI, 0.56, 0.84; P < 0.001) and higher objective response rate (ORR; 51.4% vs 25.7%) with avelumab + axitinib vs sunitinib (Motzer RJ, et al. N Engl J Med. 2019;380:1103-15). NLR has emerged as a potential prognostic biomarker in aRCC; elevated NLR is associated with poorer prognosis. Here, we describe the association of NLR with the efficacy of avelumab + axitinib from JAVELIN Renal 101. Methods: We examined baseline NLR and its association with efficacy outcomes. PFS, best overall response (per blinded independent central review using RECIST 1.1), and overall survival (OS) data from the avelumab + axitinib arm from the first interim analysis of JAVELIN Renal 101 were analyzed (data cutoff, June 20, 2018). Multivariate Cox regression analyses of PFS and OS were also conducted. Results: In the avelumab + axitinib arm, patients with < median NLR (N = 217) had longer observed PFS (stratified HR, 0.85; 95% CI, 0.634, 1.153) and longer observed OS (stratified HR, 0.51; 95% CI, 0.300, 0.871) than patients with ≥ median NLR (N = 217). The ORR was 57.1% in patients with < median NLR vs 47.5% in patients with ≥ median NLR, with complete response in 5.5% vs 1.4%. Multivariate analysis showed that low NLR was associated with longer PFS and OS by treating baseline NLR as either a continuous variable or a binary variable (dichotomized by median). Conclusions: Low NLR was associated with better observed treatment outcomes in patients with aRCC who received avelumab + axitinib. Clinical trial information: NCT02684006 .

Small cell lung cancer: Real-world data from two institutions in Lebanon for patients receiving carboplatin etoposide or atezolizumab in first line of treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20578-e20578
Author(s):  
Fadi Nasr ◽  
Reem El Khoury ◽  
Intissar Yehia ◽  
Saada Diab ◽  
Ahmad Al Ghoche ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastasis ◽  
Real World ◽  
Progressive Disease ◽  
Objective Response ◽  
Progression Free Survival ◽  
Survival Outcomes ◽  
First Line ◽  
Real World Data ◽  
Free Survival

e20578 Background: Small-cell lung cancer (SCLC), accounts for approximately 15% to 17% of all diagnosed lung cancers. It is an aggressive high-grade neuroendocrine carcinoma, diagnosed during advanced stages in the majority of patients. Despite the fact that first line treatment provides response rates of up to 80%, the majority of patients relapse within 6 months after completion of initial treatment. Few advances have been made in the management of recurrent disease and treatments patterns are poor and limited in each line of the disease. The aim of this study is to present real world data regards survival outcomes such as progression free survival and overall survival in SCLC patients receiving carboplatine etoposide or tecentriq carboplatin etoposide regimens as first line of treatment. Methods: This is a retrospective (descriptive) study on 56 patients aged ≥ 18 years and with confirmed histological SCLC. Patients with extensive stage of SCLC were enrolled in this cohort study from 2 health institutions in Lebanon from July 2007 to December 2019 and followed up until progression or death. Primary end points were overall survival (time from randomization to death from any cause) and progression free survival at 6 and 12 months (time from randomization to disease progression). Secondary endpoints included objective response rate and the duration of response. Exploratory analyses included the assessment of survival outcomes of each type of treatment according to liver and brain metastasis. Results: Overall, 56 SCLC patients, diagnosed between 2003 and 2019, were observed (age <65: (27.0%, 10 patients); ≥65 (73.0%, 41 patients)). Most often prescribed treatment were etoposide-carboplatyl (80.8%, 42 patients) and atezolizumab (19.2%10 patients). Regarding metastasis at diagnosis, liver and brain metastasis were respectively (26.8%, 11 patients) and (17.1%, 7 patients). 27patients (71.1%) were alive at 6 months without progressive disease and 13 patients (34.21 %) alive at 12 months without PD. Median progression free survival incidence since diagnosis was 8.8 months. Overall survival was 10.86 months. Objective response rate after first line was 84.2%. In a cox regression analysis, liver metastasis, brain metastasis, survival at 6 or 12 months without progressive disease did not decrease significantly PFS or OS since diagnosis. Conclusions: To our knowledge, this is the first real world clinical data on SCLC in Lebanon. This study showed limited treatment options and short survival outcomes with PFS= 8.8months and OS= 10.86 months respectively for carboplatin etoposide regimen and tecentriq carboplatin etoposide regimen. There is an essential needs for clinical comparative studies in real world practicing between treatments at each line, specially for novel treatment like atezolizumab that may present new hope and directions for SCLC.

Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): Report of LMS cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11559-11559
Author(s):  
Michael Nathenson ◽  
Edwin Choy ◽  
Neena D Carr ◽  
Hayley D Hibbard ◽  
Emanuele Mazzola ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Unacceptable Toxicity

11559 Background: Responses to single agent PD-1/PD-L1 inhibitors in STS remain limited with occasional responses in undifferentiated pleomorphic sarcomas (UPS), liposarcomas (LPS), and other sarcomas, and rare responses in leiomyosarcoma (LMS). Since cytotoxics and/or targeted therapies such as CDK4/6 inhibitors may alter the tumor microenvironment (TME) and potentiate the effect of immunotherapy, combination approaches may be needed to potentiate STS immunotherapy. The mechanism by which eribulin controls LPS may involve TME modification, and therefore it is attractive to test in combination with pembrolizumab in STS subtypes. This report summarizes the results from the LMS cohort from this ongoing trial. Methods: Pts treated with at least one prior therapy received eribulin 1.4mg/m2 (day 1, 8) and pembrolizumab 200mg (day 1), every 21 days. Pts continued therapy until progressive disease, death, or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) at 12 weeks, with 60% PFS at 12 weeks required to deem the combination promising. Tumor assessments (RECIST 1.1) were performed at screening and every 6 weeks thereafter. Secondary endpoints included overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Results: Nineteen pts with LMS were enrolled from May 2019 to Sept 2019. The median age was 62 (range 48-80). Eleven (58%) patients had uterine LMS. The median # of prior therapies was 4 (range 1-7). The median follow-up was 19.7 weeks. The PFS at 12 weeks was 42.1% (90% CI: 27.0%-65.5%), with median PFS of 11.1 weeks. Median OS was not reached during the follow-up period. There was 1 partial response, and 5 confirmed stable disease for ORR of 5.3% and CBR of 26.3%, after 12 weeks. The rate of grade 3 or higher toxicity was 68% overall, most commonly neutropenia, anemia, weight loss, diarrhea, elevations of lipase, and alkaline phosphatase. These side effects were reversible. The most common adverse events were fatigue, neutropenia, anorexia, AST increase, and nausea. Conclusions: Eribulin and pembrolizumab in LMS did not meet the predefined endpoint for efficacy. The LPS and “other STS subtype” cohorts of this trial are actively enrolling. Clinical trial information: NCT03899805 .

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