A phase I study of oncolytic immunotherapy of metastatic neuroendocrine tumors using intralesional rose bengal disodium: Cohort 1 results.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4102-4102 ◽  
Author(s):  
Timothy Jay Price ◽  
Gabby Cehic ◽  
Eric Andrew Wachter ◽  
Ian Kirkwood ◽  
Rubin Sebbon ◽  
...  
Keyword(s):  
Disease Control ◽  
Rose Bengal ◽  
Treatment Cycle ◽  
Systemic Disease ◽  
Objective Response ◽  
Neuroendocrine Neoplasms ◽  
Contrast Enhanced Ct ◽  
Patient Reported ◽  
Oncolytic Immunotherapy ◽  
Hepatic Lesions

4102 Background: Metastatic neuroendocrine neoplasms (mNEN’s) originating in the gastrointestinal tract are frequently slow growing yet both symptom and disease control remain important. Treatment options include resection, chemoablation, systemic somatostatin analogues (SSA) or peptide receptor radionuclide therapy (PRRT), but additional options are needed and one such option is hepatic intralesional (IL) rose bengal disodium (PV-10), an oncolytic immunotherapy under development for solid tumours. Methods: This phase 1 study is evaluating the safety, tolerability and reduction of biochemical markers and symptoms resulting from percutaneous administration of PV-10 in 12 subjects with progressive mNEN with hepatic lesions not amenable to resection or other potentially curative therapy. Target lesion(s) must be 1.0 - 3.9 cm in longest diameter. In Cohort 1 (n = 6) subjects receive PV-10 to a single hepatic lesion per treatment cycle, and can receive PV-10 to additional uninjected hepatic lesions ≥6 weeks after prior injection. Cohort 2 (n = 6) subjects may receive injection of multiple lesions per treatment cycle. The primary endpoint is safety. Secondary endpoints include objective response rate (ORR) assessed by contrast enhanced CT and 68Ga-DOTATATE PET, biochemical response (CgA) and patient-reported outcome (EORTC QLQ-C30 and GI.NET21). Results: Cohort 1 has fully enrolled, with 4 of 6 subjects male, median age 65yrs, range 47-72. Primary sites were: small bowel 3, pancreas 2, caecal 1; grade: Gd1 = 5, Gd2 = 1. All patients received prior SSA and PRRT. Median CgA was 645 (range 30-2819). To date 1 subject has received 4 PV-10 treatment cycles, 1 has received 2 cycles, and 4 have received a single cycle. Toxicity has been acceptable, including pain post procedure, carcinoid flare and nausea. LFT’s have remained stable. Overall QOL score was stable for 5 of 6 subjects. ORR in injected lesions is 50% (progression in 1 subject), with overall disease control of 84%. CgA response: 5 stable, 1 progression. One subject with “carcinoid pellagra” had rash resolution. Response follow-up is ongoing and additional efficacy and functional data will be presented. Conclusions: Hepatic IL PV-10 elicited no safety concerns with encouraging evidence of both local and systemic disease control. Enrolment to Cohort 2 is underway. Clinical trial information: NCT02693067.

Phase I study of autolytic immunotherapy of metastatic neuroendocrine tumors using intralesional rose bengal disodium.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4115-4115
Author(s):  
Timothy Jay Price ◽  
Gabby Cehic ◽  
Eric Andrew Wachter ◽  
Ian D. Kirkwood ◽  
Jessica Reid ◽  
...  
Keyword(s):  
Disease Control ◽  
Rose Bengal ◽  
Treatment Cycle ◽  
Phase 1 ◽  
Systemic Disease ◽  
Symptom Control ◽  
Objective Response ◽  
Neuroendocrine Neoplasms ◽  
Contrast Enhanced Ct ◽  
Patient Reported

4115 Background: Metastatic neuroendocrine neoplasms (mNEN) originating in the gastrointestinal tract are frequently slow growing yet both symptom and disease control remain important. Treatment options include resection, systemic somatostatin analogues (SSA), and systemic peptide receptor radionuclide therapy (PRRT). Additional options are needed; we have explored intralesional (IL) rose bengal disodium (PV-10), an investigational autolytic immunotherapy that can yield immunogenic cell death and disease-specific functional adaptive immunity. Methods: This phase 1 study evaluated safety, tolerability and impact on symptoms and biochemical markers resulting from IL PV-10 administered percutaneously to hepatic lesions in patients (pts) with progressive mNEN not amenable to resection or other potentially curative therapy. Eligible lesion(s) were 1.0 - 3.9 cm in longest diameter with amount of PV-10 administered proportional to size. Cohort 1 (n = 6 pts) received PV-10 to a single lesion per treatment cycle; Cohort 2 (n = 6) could receive injection to multiple lesions per treatment cycle. Pts could receive further PV-10 ≥6 weeks after prior injection. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR) assessed by contrast enhanced CT (RECIST 1.1) and 68Ga-DOTATATE PET, biochemical response (CgA) and patient-reported outcome (EORTC QLQ-C30 and GI.NET21 QOL instruments). Results: Twelve pts were enrolled, 50% male, median age 66 yrs (range 47-79). Primary sites: 7 small bowel, 2 pancreas, 1 caecal, 2 unknown; grade: Gd1 = 5, Gd2 = 7. All pts had received SSA and PRRT as part of previous therapy and all had symptomatic, progressive disease. Median CgA was 1585 (range 35-10370). One lesion was injected per cycle for all 12 pts; none were suitable for multiple injections. One pt received 4 sequential PV-10 treatment cycles, 3 received 2 cycles, and 8 received 1 cycle. Toxicity was consistent with experience in other hepatic malignancies: post-procedure pain was reported by most pts; grade 3 photosensitivity reaction occurred in 1 pt; and grade 1 elevation of hepatic enzymes attributed to PV-10 occurred in 2 pts, resolving by day 7. Additionally, carcinoid flare occurred in 1 pt. ORR of injected lesions was 42%; patient-level disease control was 84%. Estimated PFS was 9.2 months; median OS was 22.5 months. CgA remained stable in 10 pts and upregulation of NK and activated CD4+ T lymphocytes was observed post-injection. QOL data at months 1 and 3 showed stable or improved carcinoid symptoms and global health status in 9 pts. Conclusions: PV-10 elicited no safety concerns with encouraging evidence of both local and systemic disease and symptom control in a heavily pre-treated population. Multiple cycles were delivered safely in suitable patients. Adaptive immune upregulation is consistent with other solid tumors and supports potential systemic benefit. Clinical trial information: NCT02693067.

Cohort 1 results of a phase I study of autolytic immunotherapy of metastatic neuroendocrine neoplasms using intralesional rose bengal disodium.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16694-e16694
Author(s):  
Mark McGregor ◽  
Timothy Jay Price ◽  
Gabby Cehic ◽  
Ian D. Kirkwood ◽  
Ruben Sebben ◽  
...  
Keyword(s):  
Disease Control ◽  
Rose Bengal ◽  
Treatment Cycle ◽  
Phase 1 ◽  
Systemic Disease ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Hepatic Lesion ◽  
Neuroendocrine Neoplasms ◽  
Contrast Enhanced Ct

e16694 Background: Metastatic neuroendocrine neoplasms (mNEN’s) originating in the gastrointestinal tract are frequently slow growing yet both symptom and disease control remain important. Treatment options include resection, chemoablation, systemic somatostatin analogues (SSA) or peptide receptor radionuclide therapy (PRRT), but additional options are needed, especially when available options have been exhausted. Intralesional (IL) rose bengal disodium (PV-10), an autolytic immunotherapy under development for solid tumors, is being investigated as a potential option for treatment-refractory patients (pts) with hepatic metastases. Methods: This phase 1 study is evaluating the safety, tolerability and objective response resulting from percutaneous administration of PV-10 in 12 pts with progressive mNEN refractory to SSA and PPRT; pts must have at least one injectable hepatic lesion (1.0-3.9 cm in longest diameter) not amenable to resection or other potentially curative therapy. In Cohort 1 (n = 6) pts received PV-10 to a single hepatic lesion per treatment cycle, and could receive PV-10 to additional uninjected hepatic lesions ≥6 weeks after prior injection. The primary endpoint is safety. Secondary endpoints include objective response rate assessed by independent review of contrast enhanced CT and by 68Ga-DOTATATE PET. Results: Cohort 1 has fully enrolled, with 4 of 6 pts male, median age 65 yrs, range 47-72. Primary sites were: small bowel 3, pancreas 2, caecal 1. NET grade: Gd1 = 5, Gd2 = 1. All pts had progressed on prior SSA and PRRT. Median baseline CgA was 645 (range 30-2819). One pt received 4 PV-10 treatment cycles, 1 received 2 cycles, and 4 received a single cycle. Toxicity was acceptable, including transient pain post procedure, carcinoid flare and nausea. A partial response of injected lesions was observed in 50% of pts (injected lesion progression in 1 pt), with an overall response of stable disease achieved in 84% of pts by RECIST 1.1 (progressive disease in 1 pt). Progression free survival (PFS) was not reached by CT (range 2.4-25.3+ months), and was 6.1 months by PET. Median overall survival (OS) was ≥22.5 months, with three subjects alive at the data cut-off of Jan 2020 (range 18.1-33.8 months). Conclusions: Hepatic IL PV-10 elicited no safety concerns with encouraging evidence of both local response of injected tumors and prolonged systemic disease control in some pts. Enrolment to Cohort 2 is nearing completion where an additional 6 pts may receive injection of multiple lesions per treatment cycle. Clinical trial information: NCT00986661 .

scholarly journals Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial

2016 ◽  
Vol 34 (8) ◽  
pp. 786-793 ◽  
Author(s):  
George D. Demetri ◽  
Margaret von Mehren ◽  
Robin L. Jones ◽  
Martee L. Hensley ◽  
Scott M. Schuetze ◽  
...  
Keyword(s):  
Disease Control ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Prior Therapy ◽  
Risk Of Death ◽  
End Point ◽  
Patient Reported

Purpose This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients and Methods Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control—progression-free survival (PFS), time to progression, objective response rate, and duration of response—as well as safety and patient-reported symptom scoring. Results A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Conclusion Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.

scholarly journals Stereotactic Ablative Radiotherapy for the Management of Liver Metastases from Neuroendocrine Neoplasms: A Preliminary Study

2021 ◽  
Author(s):  
John Monte Hudson ◽  
Hans Tse-Kan Chung ◽  
William Chu ◽  
Amandeep Taggar ◽  
Laura Ellen Davis ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Local Control ◽  
Systemic Disease ◽  
Objective Response ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Response To Treatment ◽  
Neuroendocrine Neoplasms ◽  
Stereotactic Ablative Radiotherapy

Introduction: Liver metastases are common in patients with neuroendocrine neoplasms. The role of stereotactic ablative radiotherapy (SABR) is not well understood in this population. Objective: To evaluate the safety and efficacy of SABR in treating well-differentiated neuroendocrine liver metastases (WD-NELM). Methods: A retrospective review of patients with WD-NELM treated with SABR between January 2015-July 2019. Demographic, treatment and clinical/radiographic follow-up data were abstracted. RECIST 1.1 criteria were applied to each individual target to evaluate the response to treatment. Local control (LC) and progression free survival (PFS) were determined using Kaplan-Meier methodology. Toxicity was reported according to CTCAE v5.0. Results: Twenty-five patients with a total of 53 liver metastases treated with SABR were identified. Most patients (68%) had midgut tumors, were Grade II (80%) and had high volume intrahepatic and/or extrahepatic disease (76%). Median number of liver metastases treated was 2 with a median size of 2.5 cm. Median radiation dose delivered was 50Gy/5 fractions. Median follow-up was 14 months; 24 of the 25 patients were alive at time of analysis. The objective response rate (ORR) was 32%, with improvement or stability in 96% of lesions treated. The median time to best response was 9 months. The 1-year LC and PFS were 92% and 44% respectively. No Grade III/IV acute or late toxicity was identified. Conclusions: Liver SABR is a safe and promising means of providing local control for WD-NELM. This treatment modality should be evaluated in select patients in concert with strategies to manage systemic disease.

Chemoablation of melanoma with intralesional rose bengal (PV-10)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9060-9060
Author(s):  
S. S. Agarwala ◽  
J. Thompson ◽  
M. Smithers ◽  
M. Ross ◽  
B. Coventry ◽  
...  
Keyword(s):  
Disease Control ◽  
Rose Bengal ◽  
Phase 1 ◽  
Skin Flap ◽  
Objective Response ◽  
Safety Data ◽  
Stage Iii ◽  
Bystander Response ◽  
The Usa ◽  
Grade 3

9060 Background: Intralesional rose bengal (PV-10, a sterile 10% solution in saline) can elicit selective ablation of solid tumors and an apparent bystander response in untreated lesions. In phase 1 testing in 20 subjects with AJCC Stage III (19 subjects) or IV (1 subject) melanoma, a single injection of PV-10 into 1–20 lesions led to durable objective response (OR) at 12–24 weeks in 40% of subjects (20% CR + 20% PR by modified RECIST) and locoregional disease control (CR + PR + SD) in 75% of subjects. Untreated bystander lesions achieved an OR in 15% of subjects, and all subjects with an OR of their injected lesions achieved disease control of their bystander lesions. PV-10 was well tolerated, with only one Grade 3 adverse event (photosensitivity reaction). The most common AEs were transient pain at the treatment site (75% of subjects), followed by local inflammation or infection (25%). Methods: Expanded phase 2 testing commenced in late 2007 in up to 80 subjects with measurable Stage III or IV melanoma. After an initial treatment of 1–20 cutaneous, subcutaneous or nodal lesions, new or incompletely responsive lesions can be retreated at weeks 8, 12 or 16, with follow-up to 52 weeks. An additional 1–2 lesions, including visceral lesions, remain untreated for assessment of bystander response. Seven centers in Australia and the USA are enrolling subjects, with completion of enrolment expected by mid-2009. A modified Fleming design allows interim assessment of safety and OR at weeks 4 and 24, respectively, after treatment of the 20th and 40th subjects. The primary end-point is OR of injected lesions in the intent-to-treat population; secondary endpoints include OR of bystander lesions and PFS. Results: Interim safety data for the first 40 subjects treated is comparable to phase 1, with transient mild to moderate locoregional pain, vesicles or edema most common; Grade 3 AEs have been rare (1 case each of vesicles and skin flap necrosis), with no Grade 4 or 5 AEs attributed to PV-10. Interim efficacy for the first 20 subjects is also comparable to that of phase 1 (15% CR + 15% PR); efficacy data for the first 40 subjects will be presented at the meeting. Conclusions: The safety and efficacy profile of intralesional therapy with PV-10 compares favorably with available therapeutic options for this patient population. No significant financial relationships to disclose.

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

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.

Regorafenib plus PD-1 inhibitors in Chinese patients with microsatellite stable/mismatch repair proficient metastatic colorectal cancer: A real-world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Kaili Yang ◽  
Lu Han ◽  
Yun-Bo Zhao ◽  
Yang Ge ◽  
Qin LI ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Real World ◽  
Objective Response ◽  
Disease Control Rate ◽  
Chinese Patients ◽  
Hand Foot Syndrome

e15585 Background: A previous phase 1b trial has shown encouraging efficacy of regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of this regimen in Chinese patients in the real world. Methods: We retrospectively identified patients with MSS/pMMR mCRC who received at least one dose of programmed cell death-1 (PD-1) inhibitors plus regorafenib from 5/2019 to 2/2021 in 10 Chinese medical centers. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the safety. Results: Fifty-two patients were identified. Liver metastases were presented in 35 patients (67%). A total of 48 patients (92%) received regorafenib plus a PD-1 inhibitor as the third or later line treatment. At the data cut-off, 11 patients (21%) were still on treatment. Other patients terminated treatment because of progressive disease (45%), treatment-related adverse events (TRAEs) (14%) or treatment-unrelated deaths (6%). The median treatment cycle was 3 (range, 1-18). At a median follow-up of 4.9 months, the median OS was 17.3 months (95% CI, 10.2-NR) and the median PFS was 3.1 months (95%CI, 2.5-6.0). Baseline liver metastases were associated with inferior PFS (2.7 versus 6.3 months, p <0.05), but not OS (17.3 months versus NR, p =0.6). Among 38 patients evaluable for response, two patients (5%) achieved partial response, and 17 patients (45%) experienced stable disease as the best response. The DCR was 50% (95%CI, 5.0-NR) and was similar among different PD-1 inhibitors (Table). TRAEs were observed in 30 patients (58%). Fatigue (21%), hand-foot syndrome (19%) and rash (13%) were the most common TRAEs. Eight patients (15%) experienced grade 3-4 TRAEs, including rash (n=3), hand-foot syndrome (n=2), hypertension (n=1), myocardial enzyme elevation (n=1) and visual field loss (n=1). No treatment-related death occurred. Conclusions: The combination of regorafenib plus PD-1 inhibitors was generally tolerated and exhibited potential benefit in terms of OS and DCR. The presence of baseline liver metastases was predictive for shorter PFS but requires further investigation. Disease control rate of different PD-1 inhibitors.[Table: see text]

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

Clinical outcomes in patients (pts) with a history of central nervous system (CNS) metastases receiving talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 EMBRACA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1090-1090
Author(s):  
Jennifer Keating Litton ◽  
Johannes Ettl ◽  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Henri Roche ◽  
...  
Keyword(s):  
Stable Disease ◽  
Subgroup Analysis ◽  
Odds Ratio ◽  
Objective Response ◽  
Locally Advanced ◽  
Cns Metastases ◽  
Intracranial Disease ◽  
Patient Reported ◽  
History Of ◽  
Baseline Characteristics

1090 Background: In the EMBRACA trial (NCT01945775) of pts with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (ABC), the poly(ADP-ribose) polymerase (PARP) inhibitor TALA significantly improved progression-free survival (PFS) vs PCT (8.6 vs 5.6 mo; HR [95% CI] 0.54 [0.41-0.71]; P < 0.0001). Patient-reported outcomes favored TALA, and most common adverse events included anemia, fatigue, and nausea. Previous subgroup analyses found that pts with a history of CNS metastases had improved PFS for TALA vs PCT (HR [95% CI] 0.32 [0.15-0.68]; P = 0.0016) and improved objective response rate (ORR) 63.2% vs 15.8%, respectively (odds ratio [95% CI] 8.95 [1.86-52.26]; P = 0.0013). This retrospective subgroup analysis further explored the clinical characteristics and outcomes in pts with a history of CNS metastases in EMBRACA. Methods: Pts were randomized 2:1 to TALA or PCT. Pts with adequately treated and stable CNS metastases not requiring corticosteroids were included. This analysis assessed intracranial ORR and best overall response (BOR) based on investigator assessment per RECIST 1.1 in pts with intracranial disease at baseline (data cutoff 15-Sep-17), and overall survival (OS; data cutoff 30-Sep-19). Results: In the intent-to-treat (ITT) population, 63 pts (43/287 [15.0%] TALA and 20/144 [13.9%] PCT) had a history of CNS metastases, of which 33 (11.5%) pts (TALA) and 15 (10.4%) pts (PCT) had intracranial disease at baseline. Additional baseline characteristics are shown in the table. Intracranial ORR in pts with intracranial disease at baseline and unconfirmed complete or partial response was 18.2% (TALA) vs 20.0% (PCT) (odds ratio [95% CI] 0.78 [0.13-5.80]; P = 0.765). In pts with intracranial disease at baseline, an intracranial BOR of stable disease was 69.7% for TALA vs 33.3% for PCT. Median OS in pts with a history of CNS metastases was 12.9 mo (95% CI 9.4-15.6) for TALA and 13.4 mo (95% CI 8.8-17.6) for PCT (HR [95% CI] 0.67 [0.37-1.2]; P = 0.1936 [stratified log-rank test]). In the safety population ([n = 43, TALA]; [n = 19, PCT]), median treatment duration (range) with TALA was 5.0 (0.1-36.0) mo compared with 2.1 (0.4-6.9) mo for PCT. Conclusions: In this subgroup analysis, baseline characteristics between pts with a history of CNS metastases treated with TALA or PCT were comparable. More pts with intracranial disease at baseline treated with TALA vs PCT experienced stable disease. Intracranial ORR in pts with intracranial disease was 18.2% for TALA vs 20.0% for PCT. Treatment options for pts with a history of CNS metastases are limited and further investigation in larger data sets is warranted. Clinical trial information: NCT01945775 .[Table: see text]

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