Clinical outcomes of doxorubicin-eluting CalliSpheres® beads-transarterial chemoembolization for unresectable or recurrent esophageal carcinoma

Abstract Background The clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded CalliSpheres® beads for patients with unresectable or recurrent esophageal carcinoma have not been reported. The aim of this study is to study the clinical outcomes of DEB-TACE for patients with unresectable or recurrent esophageal carcinoma. Methods This retrospective study enrolled 21 patients (15 men; mean age 68.7 ± 9.7; range 46–86 years) with unresectable or recurrent esophageal carcinoma received DEB-TACE between July 2017 and September 2020. Patient characteristic data, imaging findings, complications and DEB-TACE procedure were reviewed. The primary endpoints, disease control rate (DCR) and objective response rate (ORR), were calculated. The secondary endpoints were overall survival rate and progression-free survival (PFS). Results Twenty-two sessions of DEB-TACE were performed in 21 patients. The technical success rate was 100%; without sever adverse events or procedure-related deaths. All patients received transarterial chemotherapy infusion with raltitrexed or oxaliplatin. The median follow-up period was 3.6 months (interquartile range, IQR 1.5–9.4 months). ORR and DCR were 42.9 and 85.7%, 28.6 and 71.4%, 20.0 and 40.0% respectively at 1-, 3-, and 6-months after DEB-TACE. The median PFS was 6.0 months, and the 3-, 6- and 12-month PFS rates were 68.2%, 45.5 and 0.0%, respectively. The median overall survival was 9.4 months, and the 3-, 6- and 12-month overall survival rates were 75.5%, 55.0 and 13.8%, respectively. Conclusions To our knowledge, this is the first study reports outcomes of DEB-TACE with doxorubicin-loaded CallSpheres bead treatment in the management of patients with unresectable or recurrent esophageal carcinoma. According to our results, this is a safe and feasible treatment modality that may be considered among the options for the treatment of these patients.

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Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.8721 ◽

2009 ◽

Vol 27 (28) ◽

pp. 4733-4740 ◽

Cited By ~ 1603

Author(s):

Henry S. Friedman ◽

Michael D. Prados ◽

Patrick Y. Wen ◽

Tom Mikkelsen ◽

David Schiff ◽

...

Keyword(s):

Overall Survival ◽

Objective Response ◽

Survival Rates ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Survival Times ◽

Open Label ◽

Noncomparative Trial ◽

End Points ◽

Free Survival

Purpose We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial. Patients and Methods One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m2 or 125 mg/m2 (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival. Results In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade ≥ 3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumab-plus-irinotecan group (grades 1, 2, and 4, respectively). Conclusion Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.

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Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-003017 ◽

2021 ◽

pp. ijgc-2021-003017

Author(s):

Christian Marth ◽

Rafal Tarnawski ◽

Alexandra Tyulyandina ◽

Sandro Pignata ◽

Lucy Gilbert ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Mismatch Repair ◽

Objective Response ◽

Progression Free Survival ◽

Open Label ◽

Phase 3 ◽

Free Survival ◽

Primary Endpoints ◽

Recurrent Endometrial Cancer

BackgroundPembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.Primary ObjectiveTo compare the efficacy and safety of first-line pembrolizumab plus lenvatinib versus paclitaxel plus carboplatin in patients with newly diagnosed stage III/IV or recurrent endometrial cancer, with measurable or radiographically apparent disease.Study HypothesisPembrolizumab plus lenvatinib is superior to chemotherapy with respect to progression-free survival and overall survival in patients with mismatch repair-proficient tumors and all patients (all-comers).Trial DesignPhase 3, randomized (1:1), open-label, active-controlled trial. Patients will receive pembrolizumab intravenously every 3 weeks plus lenvatinib orally daily or paclitaxel plus carboplatin intravenously every 3 weeks, stratified by mismatch repair status (proficient vs deficient). Patients with mismatch repair-proficient tumors will be further stratified by Eastern Cooperative Oncology Group performance status (0/1), measurable disease (yes/no), and prior chemotherapy and/or chemoradiation (yes/no).Major Inclusion/Exclusion CriteriaAdults with stage III/IV/recurrent histologically confirmed endometrial cancer that is measurable or radiographically apparent per blinded independent central review. Patients may have received previous chemotherapy only as neoadjuvant/adjuvant therapy and/or concurrently with radiation. Patients with carcinosarcoma (malignant mixed Müllerian tumor), endometrial leiomyosarcoma, or other high grade sarcomas, or endometrial stromal sarcomas were excluded.Primary EndpointsProgression-free and overall survival (dual primary endpoints).Sample SizeAbout 875 patients.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment is expected to take approximately 24 months, with presentation of results in 2022.Trial RegistrationClinicalTrials.gov, NCT03884101.

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Three-year overall survival update from the PACIFIC trial.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.8526 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 8526-8526 ◽

Cited By ~ 9

Author(s):

Jhanelle Elaine Gray ◽

Augusto E. Villegas ◽

Davey B. Daniel ◽

David Vicente ◽

Shuji Murakami ◽

...

Keyword(s):

Overall Survival ◽

Survival Rates ◽

Progression Free Survival ◽

Standard Of Care ◽

Smoking History ◽

Rank Test ◽

Kaplan Meier ◽

Primary Endpoints ◽

The Pacific ◽

Patient Reported

8526 Background: In the phase 3 PACIFIC study of patients with unresectable, Stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (HR, 0.52; 95% CI, 0.42–65; P < 0.0001) and overall survival (OS; HR, 0.68; 95% CI, 0.53–0.87; P = 0.00251). Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. Methods: Patients with WHO PS 0/1 (any tumor PD-L1 status) who received ≥2 cycles of platinum-based CRT were randomized (2:1), 1–42 days following CRT, to receive durvalumab 10 mg/kg intravenously every 2 weeks or placebo, up to 12 months, and stratified by age, sex, and smoking history. OS was analyzed using a stratified log-rank test in the ITT population. Medians and OS rates at 12, 24 and 36 months were estimated by Kaplan-Meier method. Results: In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. As of January 31, 2019 (data cutoff), 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months (range, 0.2–51.3). Updated OS remained consistent with that previously reported (stratified HR 0.69, 95% CI, 0.55–0.86), with the median not reached (NR; 95% CI, 38.4 months–NR) with durvalumab versus 29.1 months (95% CI, 22.1–35.1) with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. After discontinuation, 43.3% and 57.8% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy (9.7% and 26.6% subsequently received immunotherapy). OS subgroup results will be presented. Conclusions: Updated OS data from PACIFIC, including 3-year survival rates, underscore the long-term clinical benefit with durvalumab following CRT and further establish the PACIFIC regimen as the standard of care in this population. Clinical trial information: NCT02125461.

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Survival of patients with intermediate stage hepatocellular carcinoma treated with superselective transarterial chemoembolization using doxorubicin-loaded DC Bead under cone-beam computed tomography control

Radiology and Oncology ◽

10.1515/raon-2015-0045 ◽

2016 ◽

Vol 50 (4) ◽

pp. 418-426 ◽

Cited By ~ 7

Author(s):

Peter Popovic ◽

Borut Stabuc ◽

Rado Jansa ◽

Manca Garbajs

Keyword(s):

Computed Tomography ◽

Overall Survival ◽

Cone Beam Computed Tomography ◽

Transarterial Chemoembolization ◽

Tumor Response ◽

Objective Response ◽

Survival Rates ◽

Intermediate Stage ◽

Response To Treatment ◽

Cone Beam

Abstract Background The purpose of this retrospective study was to evaluate treatment response, adverse events and survival rates of patients with intermediate stage HCC treated with superselective doxorubicin-loaded DC Bead transarterial chemoembolization (DEBDOX) under cone beam computed tomography (CBCT) control. Patients and methods Between October 2010 and June 2012, 35 consecutive patients with intermediate stage HCC (32 male, 3 female; average age, 67.5 ± 7.8 years; 22 patients Child-Pugh class A, 8 class B, 5 without cirrhosis) were treated with DEBDOX TACE. Portal vein thrombosis was observed in 6 (17.1%) patients. DEBDOX TACE was performed by superselective catheterization of feeding vessels followed by embolization with 100-300 μm microspheres loaded with 50-100 mg of doxorubicin. In all cases, CBCT was used during chemoembolization. Tumor response rates were defined according to mRECIST criteria. Results Overall, 120 procedures were performed (mean, 3.2 per patients). We treated 97 lesions with an average diameter of 4.9 ± 1.9 cm. There were 32 minor and 2 (1.6%) major complications (one liver abscess and one cerebrovascular insult). After a mean follow-up of 27.7 ± 10.5 months, 94.3% of patients achieved an objective response to treatment (42.4% complete response and 57.6% partial response). Mean time to progression was 10.9 ± 5.3 months. Mean overall survival was 33.9 months (95% CI; 28.9 – 38.9 months), with 1- and 2- year survival of 97.1% and 65.7%, respectively. Conclusions Superselective DEBDOX TACE performed under CBCT control is a safe and effective method with high rates of tumor response and overall survival.

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Efficacy and Safety of DEB-TACE for Patients With Hepatocellular Carcinoma With the Largest Tumor Diameter ≥7 cm

10.21203/rs.3.rs-109420/v1 ◽

2020 ◽

Author(s):

Wei Chen ◽

Bei Lu ◽

Mengzeng Zhang ◽

Zhenguo Hou

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Transarterial Chemoembolization ◽

Cox Regression ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Diameter ◽

Tace Group ◽

Huge Hepatocellular Carcinoma

Abstract Objective: To explore the effectiveness and safety of DEB-TACE in patients with primary huge hepatocellular carcinoma. Methods: From January 2017 to January 2019, 87 patients with huge unresectable HCC were retrospectively analyzed. 48 cases received drug-elutted beads for transarterial chemoembolization (DEB-TACE group), and 39 cases received conventional transarterial chemoembolization (c-TACE group). The tumor treatment response, overall survival (OS), progression-free survival (PFS), the incidence of adverse events (AEs) were compared between the two groups and the factors influencing OS were analyzed. Results: The median follow-up was 295 days (ranges 78 to 603 days). There was no statistical difference in baseline characteristics and follow-up treatment between the two groups. The objective response rate(ORR) of DEB-TACE group was higher than that of c-TACE group within 3 months after treatment. The change was similar in the incidence of AEs between the two groups; DEB-TACE group showed longer PFS and OS than c-TACE group. Cox-regression multivariate analysis showed that DEB-TACE was an important factor affecting the overall survival. Conclusion: DEB-TACE prolonged the survival time of patients with huge unresectable HCC and could be a better choice than c-TACE without increasing the incidence of AEs.

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Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

Current Oncology ◽

10.3390/curroncol28010078 ◽

2021 ◽

Vol 28 (1) ◽

pp. 813-817

Author(s):

Arielle Elkrief ◽

Suzanne Kazandjian ◽

Thierry Alcindor

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Objective Response ◽

Case Series ◽

Progression Free Survival ◽

Distant Metastases ◽

First Line ◽

Pleomorphic Sarcoma ◽

Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

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Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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637 Immune-related adverse events (irAEs) may indicate a favorable prognosis in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICI)

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0637 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A672-A673

Author(s):

Dylan Martini ◽

Sean Evans ◽

Subir Goyal ◽

Yuan Liu ◽

T Anders Olsen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Adverse Events ◽

Clinical Outcomes ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Free Survival ◽

Kaplan Meier ◽

Emory University

BackgroundImmune checkpoint inhibitors (ICI) have become an increasingly utilized treatment in metastatic renal cell carcinoma (mRCC). Although they have a favorable toxicity profile, immune-related adverse events (irAEs) can have a significant impact on patients‘ quality of life. It is not well understood whether irAEs are associated with improved clinical outcomes. We investigated the relationship between irAEs and clinical outcomes in mRCC patients treated with ICI.MethodsWe performed a retrospective study of 200 patients with mRCC who received ICI at Winship Cancer Institute of Emory University from 2015–2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from ICI-initiation to date of death and radiographic or clinical progression, respectively. CB was defined as a best radiographic response of complete response (CR), partial response (PR), or stable disease (SD) for >6 months per response evaluation criteria in solid tumors (RECIST) version 1.1. Toxicity data was collected from clinic notes and laboratory values. The association with OS and PFS was modeled by Cox proportional hazards model. Kaplan-Meier curves were created for survival estimates.ResultsMost patients were males (71%), and 78% had clear-cell RCC (ccRCC). Most patients (58%) received anti-PD-1 monotherapy. The majority were international mRCC database consortium (IMDC) intermediate (57%) or poor-risk (26%). Anti-PD-1 monotherapy was the most common (58%) treatment regimen and most patients received ICI as first (38%) or second-line (42%) treatment. One-third of patients (33%) experienced an irAE, with the most common being endocrine (13%), gastrointestinal (11%), and dermatologic (10%). Patients who experienced irAEs had significantly longer OS (HR: 0.52, 95% CI: 0.32–0.87, p=0.013), higher chance of CB (OR: 2.10, 95% CI: 1.11–4.00, p=0.023) and showed a trend towards longer PFS (HR: 0.71, 95% CI: 0.49–1.02, p=0.065) in MVA (table 1). Patients who had thyroid irAEs had significantly longer OS, PFS, and higher chance of CB in MVA (table 1). The objective response rate was higher for patients who experienced irAEs (34% vs. 18%). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p=0.005) and PFS (7.5 vs 3.6 months, p=0.0028) compared to patients who did not (figure 1).Abstract 637 Table 1MVA* of association between irAEs and clinical outcomesAbstract 637 Figure 1Kaplan-Meier curves of association between immune-related adverse events (irAEs) and overall survival (OS, top panel) and progression-free survival (PFS, bottom panel)ConclusionsWe showed that mRCC patients who experienced irAEs, particularly thyroid irAEs, had improved clinical outcomes. This suggests that irAEs may be prognostic of favorable outcomes in mRCC patients treated with ICI. Larger, prospective studies are needed to validate these findings.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNot applicableEthics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicableReferencesNot applicable

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EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem

Neuro-Oncology ◽

10.1093/neuonc/noab196.357 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi91-vi91

Author(s):

Yeonju Kim ◽

Terri Armstrong ◽

Mark Gilbert ◽

Orieta Celiku

Keyword(s):

Central Nervous System ◽

Overall Survival ◽

Clinical Trials ◽

Nervous System ◽

Brain Tumor ◽

Objective Response ◽

Survival Rates ◽

Maximum Tolerated Dose ◽

Secondary Outcome ◽

Patient Reported

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.

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Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4096 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4096-4096

Author(s):

Sophie Cousin ◽

Carine A. Bellera ◽

Jean Philippe Guégan ◽

Thibault Mazard ◽

Carlos A. Gomez-Roca ◽

...

Keyword(s):

Phase Ii ◽

Adaptive Design ◽

Objective Response ◽

Locally Advanced ◽

Survival Rates ◽

Previous Treatment ◽

Progression Free Survival ◽

Treatment Interruption ◽

Clinical Activity ◽

Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

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