Use of yttrium-90 (Y90) glass microspheres (TheraSphere) as neoadjuvant to transplantation/resection in hepatocellular carcinoma: Analyses from the LEGACY study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 300-300
Author(s):  
Robert Lewandowski ◽  
Guy E. Johnson ◽  
Edward Kim ◽  
Ahsun Riaz ◽  
Vivian Bishay ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Partial Response ◽  
Neoadjuvant Therapy ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
The United States ◽  
Glass Microspheres ◽  
Eligibility Criteria ◽  
Yttrium 90

300 Background: The objective of the LEGACY study was to assess the Objective Response Rate (ORR) and Duration of Response (DoR) following treatment with Yttrium-90 (Y90) glass microspheres in patients with unresectable solitary hepatocellular carcinoma (HCC). The objective of the analyses presented here are to evaluate ORR, DoR, and Overall Survival (OS) by transplant/resection status and to compare these outcomes with patients who did not go on to transplantation/resection after receiving treatment with Y90. Methods: LEGACY is a single-arm, multicenter, retrospective study of patients with unresectable HCC who received treatment with Y90 glass microspheres (TheraSphere) at one of three sites in the United States. LEGACY included all consecutive eligible patients who received treatment between January 2014 and December 2017 and met the eligibility criteria (Child-Pugh A; ECOG score of 0 or 1; BCLC A or C; and a solitary tumor > 2 and ≤8 cm). Primary efficacy endpoints included ORR and DoR. ORR included patients who achieved either a complete response or partial response based on localized mRECIST; response was assessed via blinded, independent, central review. Secondary endpoints include OS and number and type of subsequent treatments, including transplantation and resection. Results: Among all 162 patients enrolled in LEGACY, ORR was 72.2% (117/162; 95% CI = 64.9%, 78.5%); the majority of patients experienced DoR ≥ 6 months (89/117, 76.1%, 95% CI = 67.6%, 82.9%). Median follow-up time for all 162 patients enrolled in LEGACY was 29.9 months by reverse Kaplan-Meier analysis; 3-year OS was 86.6%. For 45/162 (27.8%) of patients, Y90 treatment served as neoadjuvant therapy; 34 went on to transplantation (21.0%) and 11 (6.8%) went on to resection. For neoadjuvant treatment, ORR was 80.0% (36/45, 95% CI = 66.2, 89.1), DoR ≥ 6 months was 30.6% (11/45, 95% CI = 18.0, 46.9), and 3-year OS was 92.8% (95% CI = 74.2, 98.2). Of these 45 patients, 35 patients achieved complete response (CR), 1 achieved partial response (PR), and 9/45 (20.0%) were deemed not evaluable as they underwent surgery prior to the 6-month mark and did not have imaging assessments post-Day 46. These nine patients were censored, lowering the DoR; however, histopathology revealed that 7/9 (77.8%) achieved complete pathologic necrosis, 1/9 (11.1%) had extensive pathologic necrosis, and 1 (11.1%) had partial pathologic necrosis. For the 117/162 (72.2%) patients who did not go on to surgical treatment, ORR was 91.5% (107/117, 95% CI = 85.0, 95.3), DoR ≥ 6 months was 72.9% (78/117, 95% CI = 63.8, 80.4), and 3-year OS was 83.5% (95% CI = 72.2, 90.5). Conclusions: Treatment of solitary unresectable HCC with Y90 glass microspheres provides strong ORR, DoR, and OS both as neoadjuvant therapy to transplantation/resection and as treatment in non-surgical candidates.

scholarly journals P01.01 Safety and Efficacy Study of Pembrolizumab in Combination With LENvatinib in Participants With Hepatocellular Carcinoma (HCC) Before Liver Transplant as Neoadjuvant TherapY——PLENTY Randomized Clinical Trial

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A3.1-A3
Author(s):  
H Feng ◽  
Q Xia ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Neoadjuvant Therapy ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
Milan Criteria ◽  
Full Time ◽  
Safety And Efficacy ◽  
Neoadjuvant Immunotherapy ◽  
Block Randomization

BackgroundPatients with hepatocellular carcinoma (HCC) who exceed standard Milan criteria suffered from high post-transplant recurrence rate.This study will evaluate the safety and efficacy of pembrolizumab in combination with lenvatinib as neoadjuvant therapy in participants with HCC exceeding Milan criteria before liver transplant.Materials and MethodsParticipates would be randomly assigned (1:1) to experimental or Comparator/Control by computer-generated allocation based on the envelope method and the hierarchical block randomization method(hierarchy: BCLC stage and AFP level). The envelopes are sealed opaque, and sequentially numbered.Randomization is performed by the trial coordinator.The random number table and the block assignment number table will be kept confidential by the full-time secretary of this project.Center-stratified block-permuted randomization is used in this trial. Then permuted block randomization is used for each stratum with a block size of 4.ResultsThe initial first patient was recruited in August.2020, the primary hypothesis of this study are that neoadjuvant pembrolizumab plus lenvatinib is superior to regularly waiting in the list with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) Objective Response Rate (ORR).The investigators design a clinical study to explore whether the combination above as a neoadjuvant treatment in patients with advanced HCC before liver transplant could reduce postoperative recurrence and to analyze potential immune biomarker of therapeutic response.ConclusionsThe study is still ongoing and the preliminary short term outcome was positive. HCC patients who exceeded milan criteria may benefit from neoadjuvant immunotherapy combined with TKI before liver transplantation.Disclosure InformationH. Feng: None. Q. Xia: None.

scholarly journals Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Myung Ji Goh ◽  
Joo Hyun Oh ◽  
Yewan Park ◽  
Jihye Kim ◽  
Wonseok Kang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Disease Progression ◽  
Real World ◽  
Medical Center ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Background:</i></b> Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. <b><i>Methods:</i></b> A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. <b><i>Results:</i></b> A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. <b><i>Conclusion:</i></b> Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

scholarly journals CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 516
Author(s):  
Daan Linders ◽  
Marion Deken ◽  
Maxime van der Valk ◽  
Willemieke Tummers ◽  
Shadhvi Bhairosingh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Pathological Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Response Evaluation ◽  
Tumor Bed ◽  
Upar Expression ◽  
Diagnostic Biopsy

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Therapeutic Effects

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.

RA03.05: COMPARISON OF OUTCOME OF ESOPHAGECTOMY VERSUS NON-SURGICAL TREATMENT FOR RESECTABLE ESOPHAGEAL CANCER WITH CLINICAL COMPLETE RESPONSE TO NEOADJUVANT THERAPY

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 24-24
Author(s):  
Shuhei Koga ◽  
Yu Ohkura ◽  
Masaki Ueno ◽  
Harushi Udagawa
Keyword(s):  
Esophageal Cancer ◽  
Surgical Treatment ◽  
Neoadjuvant Therapy ◽  
Neoadjuvant Treatment ◽  
Residual Tumor ◽  
Complete Response ◽  
Intergroup Difference ◽  
Clinical Complete Response ◽  
Significant Intergroup Difference ◽  
Non Surgical Treatment

Abstract Background Treatment for patients who have achieved clinical complete response (cCR) after neoadjuvant therapy has not been established, with no consensus regarding the indications for either esophagectomy or non-surgical treatment. Methods Among 1545 patients with esophageal cancer at Toranomon Hospital between January 2006 and August 2017, 39 who achieved cCR after neoadjuvant treatment were divided into two groups according to treatment: esophagectomy group (n = 18) andtreatment group (n = 21) for comparison. Results No significant intergroup difference was observed in baseline characteristics. Pathological complete response was confirmed in 13 (72.2%) of the 18 patients who underwent esophagectomy, while residual tumor was detected at the location of primary tumor in 2 (11.1%) patients and lymph node metastasis was found in 3 (16.7%) patients. Recurrence-free survival (RFS) was significantly longer in the esophagectomy group than in the non-surgical group (P = 0.002). Disease-specific survival (DSS) was significantly longer in the esophagectomy group (P = 0.007). However, no significant intergroup difference was observed in overall survival estimated based on all deaths, including (P = 0.451). Conclusion With improved diagnostic accuracy, non-surgical treatment can be an option for patients estimated as cCR after treatment administered in a neoadjuvant setting. However, surgical resection is considered more appropriate because of residual tumor in some patients with cCR and because of superior DSS and RFS following esophagectomy compared with non-surgical treatment. Future studies must focus on ameliorating late postoperative complications such as respiratory failure and aspiration pneumonia. Disclosure All authors have declared no conflicts of interest.

Defibrotide (DF) In the Treatment of Severe Hepatic Veno-Occlusive Disease (VOD) with Multi-Organ Failure (MOF): Results of a Treatment IND Expanded Access Protocol

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 906-906 ◽  
Author(s):  
Paul Richardson ◽  
Angela Smith ◽  
Sally Arai ◽  
Stephan A. Grupp ◽  
Nancy A Kernan ◽  
...  
Keyword(s):  
Late Onset ◽  
Pulmonary Hemorrhage ◽  
Complete Response ◽  
The United States ◽  
Best Supportive Care ◽  
Study Entry ◽  
Phase 3 ◽  
Eligibility Criteria ◽  
Rank Analysis ◽  
Common Diagnosis

Abstract Abstract 906 Background: Single-arm Phase 2 trials of DF in the treatment of severe VOD/MOF post-SCT demonstrated a complete response (CR) in 36–46% of patients (pts). A subsequent Phase 3 trial enrolling pts with more severe VOD (28%/24% with ventilator/dialysis dependence at study entry vs 5%/7%) demonstrated a CR of 24% compared to 9% in a matched Historical Control (HC); p=0.0148; Richardson ASH 2009). Given the life-threatening nature of VOD/MOF, DF was made available in the United States through a Treatment IND protocol (T-IND) in December 2007 to gather additional safety and response data. Methods: Pts were required to have a diagnosis of VOD based upon Baltimore criteria (total bilirubin ≥ 2.0 mg/dL with ≥ 2 of the following: hepatomegaly, ascites or 5% weight gain) with MOF (either renal and/or pulmonary failure). Pts without a Baltimore diagnosis could enroll with biopsy-proven evidence of VOD. Eligibility criteria were expanded to permit patients with late onset VOD (VOD diagnosed after 21 days (d) or VOD/MOF after 28d post-SCT). Key exclusion criteria included clinically significant bleeding or need for >1 pressor to maintain BP. CR was defined as bilirubin < 2 mg/dL + resolution of MOF. Mortality was assessed at D+100. DF was given at 6.25 mg/kg IV q6h (25 mg/kg/d); treatment duration was recommended for at least 21d. Results: This interim analysis is based on 104 pts enrolled between14Dec2007-29Sep2009 and treated at 36 institutions. Most sites (n=23) enrolled only 1–2 pts. Nearly all pts (n=98) had undergone prior SCT; 6 had prior chemotherapy only; and 29 pts had late onset VOD post-SCT. Of the SCT pts, 69 pts enrolled in the T-IND met eligibility criteria for the original Phase 3 trial. Baseline demographics included median age 17 years (range 0.1 – 66); 59% male; and 16% with prior SCT. The most common diagnosis was leukemia (30% AML; 22% ALL; 7% other leukemia). The majority of pts had undergone allogeneic SCT (88%) with conditioning consisting of cyclophosphamide (76%), busulfan (42%) and/or TBI (41%). Mean onset of VOD post-SCT was 17 days. At entry, 20% of pts were dialysis dependent; 28% were ventilator dependent. Mean number of days of DF administration was 20 (range 2–88). Of the 104 pts, 36 (35%) achieved a CR by D+100. For the various sub-populations, the CR by D+100 rate was 24% for pts with late-onset VOD (n=29); 35% for those pts undergoing SCT (n=98); and 39% for the 69 pts who matched the entry criteria for the Phase 3 trial. Comparison of this group of 69 pts to the Phase 3 HC showed a statistically improved outcome (p=0.0007). Similar to the Phase 3 results, the CR rate was higher in pts who were not on dialysis/ventilator at study entry (41% vs 23%). Although children had previously been noted to have a higher CR rate in prior studies, the CR rate in the T-IND was similar in children compared to adults (35% and 34%, respectively). Overall D+100 mortality rate equaled 61% (n=104). Comparing the 69 pts who met Phase 3 entry criteria, D+100 mortality was 58% (p=0.0465 compared to the HC using Kaplan Meier estimates by log-rank analysis). Toxicity proved manageable: 11 pts experienced a total of 13 drug-related AEs including pulmonary hemorrhage (n=5), GI hemorrhage (n=3), hypotension (n=2), rectal hemorrhage, cerebral hemorrhage and pulmonary alveolar hemorrhage (1 pt each). Overall, 10% of pts experienced a drug-related toxicity that led to discontinuation. Similar to the observation of decreased GvHD in pediatric pts undergoing SCT who received prophylactic DF compared to best supportive care, the incidence of all grade GvHD was relatively low (8%). Conclusions: In 104 pts with severe VOD/MOF enrolled at 36 US institutions, use of DF demonstrated a 35% CR by D+100. Comparing those pts who met criteria for the Phase 3 trial to the HC used in that study, D+100 CR and survival were significantly improved in this study population. DF-associated toxicities are consistent with prior studies. Following an amendment in 30Sep2009, entry criteria for the T-IND study were expanded to permit enrollment of pts without SCT (VOD post chemotherapy) as well as pts without MOF to evaluate earlier intervention. Analysis of this group will be performed separately. Enrollment into the T-IND study continues. Disclosures: Richardson: Gentium: Membership on an entity's Board of Directors or advisory committees. Massaro:Gentium: Consultancy. Hannah:Gentium: Consultancy. Iacobelli:Gentium: Employment.

Oral vinorelbine (NVBo) and anastrozole (A) as neoadjuvant treatment of locally advanced (LA) breast cancer (BC) in hormone receptor positive (HR+) postmenopausal patients: Results of an international phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 600-600
Author(s):  
M. Riggi ◽  
E. M. Moreno-Lopez ◽  
J. Rolski ◽  
P. Petruzelka ◽  
J. M. Ferrero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Conservative Surgery ◽  
Ultra Sound ◽  
Oral Vinorelbine ◽  
Hormone Receptor Positive

600 Background: Two recent randomized studies with anastrozole, as single agent or with an unspecified cytotoxic, produced an objective response rate (RR) of 24 and 39.5% by ultra-sound (US) [baseline primary tumor diameters (PTD) of 2.6 cm (median) and 3.6 cm (mean), respectively] in LA BC. This trial assessed the effect of the combined NVBo-A therapy. Methods: 55 assessable HR+ patients (pts) with LA breast cancer (tumor size > 3 cm) were expected, including 10 with pharmacokinetics (PK). Pts received 3 (if progression or complete response) to 6 courses of NVBo at day 1(D1) and 8 every 3 weeks (60 mg/m2 escalated to 80 mg/ m2 at cycle 2) with 1 mg of A daily. Both US (primary criteria) and calliper assessments were performed at cycle 3 and 6, with surgery within 4 weeks of the last D1 NVBo. Anastrozole interaction on NVBo was studied by comparing NVBo PK between D1 and D8. NVBo interaction on A was assessed by comparing trough concentrations between D8 and D21. Results: Between July 2005 and June 2008, 60 women were enrolled. The first 58 pts were analyzed: at baseline, median age 64.9 years, median and mean PTD 3.7 and 4 cm, respectively; 59% N1–2(17% N2), with a feasible breast conservative surgery (BCS) in only 12%; 19% were inoperable. The RR was 59% (95% CI 45–71%) by US and 69% (55–80%) by calliper. Clinical nodal invasion on TNM (N+) regressed by 32%. 10/11 inoperable pts at baseline became operable. Among 51 resections (concurrent events 4 pts, unresectable 3 pts) 20% were BCS. The pCR was 3.9%. Grade (G) 3–4 toxicities: haematological toxicities (neutropenia) in 6 pts; hepatic enzymes G3 1 pt; gastrointestinal toxicities G3 5 pts and 1 G4 musculoskeletal pain. PK interim analysis showed an absence of interaction between the 2 drugs. Conclusions: NBVo plus A led to an increased RR compared with previous experiences with A alone or not (IMPACT, PROACT trials). The operability rate was notably improved from baseline in this population with unfavorable characteristics and BCS was slightly increased. This combination treatment was well tolerated and pts could benefit from an oral therapy allowing preservation of daily living activities. [Table: see text]

Phase III Randomized Controlled Trial Comparing the Survival of Patients With Unresectable Hepatocellular Carcinoma Treated With Nolatrexed or Doxorubicin

2007 ◽  
Vol 25 (21) ◽  
pp. 3069-3075 ◽  
Author(s):  
Robert G. Gish ◽  
Camillo Porta ◽  
Lucian Lazar ◽  
Paul Ruff ◽  
Ronald Feld ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Karnofsky Performance Status ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Phase Iii ◽  
Study Objective

PurposeThe study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX).Patients and MethodsPatients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score.ResultsAt the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm.ConclusionNOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update

2017 ◽  
Vol 106 (4) ◽  
pp. 307-311 ◽  
Author(s):  
Emilio Bajetta ◽  
Laura Catena ◽  
Sara Pusceddu ◽  
Francesca Spada ◽  
Claudio Iannacone ◽  
...  
Keyword(s):  
Partial Response ◽  
Neuroendocrine Tumors ◽  
Objective Response ◽  
Study Drug ◽  
Complete Response ◽  
Neuroendocrine Neoplasms ◽  
First Line ◽  
Primary Tumor Site ◽  
Long Acting ◽  
Line Setting

Background: We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. Methods: Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of “long responder” patients and of time to progression (TTP) and overall survival (OS) at 5 years. Results: Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). Conclusion: In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.

Sign in / Sign up

Export Citation Format

Share Document