Everolimus (EVE) plus endocrine therapy in patients with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (BC): First- and second-line data from the BOLERO-4 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1010-1010 ◽  
Author(s):  
Fatima Cardoso ◽  
Cristian Villanueva ◽  
Melanie Royce ◽  
Felipe Cruz ◽  
Marc Debled ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adverse Events ◽  
Disease Progression ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Second Line ◽  
Prior Therapy ◽  
Estrogen Receptor Positive

1010 Background: Initial first-line (1L) data from the phase 2 BOLERO-4 (NCT01698918) study of EVE + letrozole (LET) in postmenopausal patients (pts) with ER+, HER2− metastatic BC (MBC) or locally advanced BC (LABC) have been previously reported. Here, we present updated 1L progression-free survival (PFS) data, plus new data describing second-line (2L) EVE + exemestane (EXE) in pts with disease progression after EVE + LET. Methods: Postmenopausal pts with ER+, HER2− MBC or LABC with no prior therapy for advanced disease received EVE 10 mg/day + LET 2.5 mg/day. After disease progression, pts could receive EVE + EXE 25 mg/day until further disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint: 1L PFS. Secondary endpoints: overall response rate (ORR), clinical benefit rate (CBR), 2L PFS, overall survival (OS), and safety (1L and 2L). Results: Among 202 pts (median age, 64 years) with 1L MBC (96%) or LABC (4%), median PFS (95% CI) was 21.7 (18.1–23.9) months, ORR was 43.6%, and CBR was 74.3%. 42 pts (median age, 62 years) with MBC (88%) or LABC (12%) who progressed on 1L EVE + LET received optional 2L EVE + EXE. 2L median PFS (95% CI) was 3.7 (1.8–9.1) months, ORR was 4.8%, and CBR was 21.4%. Common 1L adverse events (all grades, regardless of drug relationship) were stomatitis (69%), weight loss (44%), diarrhea (40%), nausea (37%), and anemia (35%); 2L adverse events included stomatitis (19%) and weight loss (19%). Median duration of follow-up from start of 1L to the data cutoff for these new analyses (17 June 2016) was 23.5 months. OS will be analyzed at a later data cut. Conclusions: EVE + LET is an effective regimen in 1L ER+, HER2− advanced BC. Thesedata support previously reported BOLERO-2 data demonstrating a PFS improvement from addition of EVE to an aromatase inhibitor. 2L data, although limited by the small number of pts, show preliminary evidence of EVE activity when continued beyond disease progression. No new safety signals were seen. Lower rates of stomatitis in 2L were noted. Clinical trial information: NCT01698918.

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

2012 ◽  
Vol 30 (13) ◽  
pp. 1484-1491 ◽  
Author(s):  
José Baselga ◽  
José Getúlio Martins Segalla ◽  
Henri Roché ◽  
Auro del Giglio ◽  
Hélio Pinczowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Mucosal Inflammation ◽  
Second Line ◽  
Double Blind ◽  
Multikinase Inhibitor

PurposeSorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) –negative breast cancer.Patients and MethodsPatients were randomly assigned to first- or second-line capecitabine 1,000 mg/m2orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS).ResultsIn total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively).ConclusionAddition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

A retrospective analysis of apatinib in advanced non-small cell lung cancer patients refractory to chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20562-e20562 ◽  
Author(s):  
Jianping Xu ◽  
Xiaoyan Liu ◽  
Sheng Yang ◽  
Xiangru Zhang ◽  
Yuankai Shi
Keyword(s):  
Adverse Events ◽  
Brain Metastases ◽  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Second Line ◽  
Lung Cancer Patients ◽  
Hand Foot Syndrome ◽  
Line Setting

e20562 Background: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. A phase II clinical study proved that 750 mg qd apatinib showed clinical benefit in patients with advanced non-squamous NSCLC refractory to two or more lines of chemotherapy (Zhang et al. 2012 ASCO, 7548). In this retrospective study, we assessed the efficacy of apatinib at a more frequently used dose of 500 mg qd in advanced chemo-refractory NSCLC. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. Methods: Clinical data of 25 advanced NSCLC patients who received oral apatinib 500 mg once daily as second-line and beyond therapy between August 2015 and May 2016 were reviewed. Results: The median progression-free survival (PFS) was 5.17 months (95% CI: 0.76–9.57 months). The response rate (RR) and disease control rate (DCR) were 8.0% and 68.0%, respectively. In the second-line setting (n=13), the mPFS was 7.37 months (95% CI: 0.01–14.72 months), and the RR and DCR were 0.0% and 61.5%, respectively. In the third-line and beyond setting (n=12), the mPFS was 5.17 months (95% CI: 1.78–8.55 months), and the PR and DCR were 16.7% and 75.0%, respectively. The DCR was 57.1% for 7 patients with brain metastases following apatinib administration. All patients were well tolerant to apatinib without any Grade 3 or 4 adverse events. The most common Grade 1 or 2 adverse events included hypertension (72.0%), hand-foot syndrome (24.0%), fatigue (24.0%), abnormal liver function (20.0%), nausea (12.0%) and palpitation (8.0%). Conclusions: Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dose of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases.

Results of a phase II trial of ramucirumab plus irinotecan as second-line treatment for patients with advanced gastric cancer (HGCSG 1603).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 217-217
Author(s):  
Yasuyuki Kawamoto ◽  
Satoshi Yuki ◽  
Kentaro Sawada ◽  
Michio Nakamura ◽  
Osamu Muto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Therapy ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Primary Endpoint ◽  
Causal Relation ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line

217 Background: Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody. The RAINBOW trial showed RAM plus paclitaxel (PTX) increased overall survival (OS) compared with PTX alone for advanced gastric cancer (AGC) in second-line treatment. WJOG 4007 trial demonstrated equivalent efficacy between irinotecan (IRI) and PTX. We conducted this trial to examine the efficacy and safety of RAM plus IRI combination therapy in the second-line treatment for AGC. Methods: This non-randomized, single arm, phase 2 trial was carried out at 22 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM 8 mg/kg and IRI 150 mg/m2 combination therapy administered every two weeks were continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint was progression-free survival (PFS) rate at six-month, the target was set as 16% with an expected threshold of 39%. A total of 35 cases are planned for registration. The secondary endpoints were OS, PFS, response rate (RR) and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011180029. Results: Between Jan 2018 and Sept 2019, 35 patients were enrolled. Median age was 70 (range, 47-80); female/male were 10/25; ECOG PS 0/1, 22/13. PFS rate at six months was 26.5% (95%C.I., 13.2-41.8%, p = 0.1353). Median PFS and OS were 4.2 (95%C.I., 2.5-5.4 months) and 9.6 months (95%C.I., 6.5-16.6 months), respectively. RR was 26% and disease control rate was 85%. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), febrile neutropenia (11%), diarrhea (9%), hypertension (9%), proteinuria (9%), hypokalemia (9%), hypoalbuminemia (9%), thrombocytopenia (6%), and hyponatremia (6%). No death and new safety signals with a causal relation to study treatment were observed. Conclusions: Although the primary endpoint was not achieved statistically, the results are clinically encouraging, especially take into account that more elderly patients enrolled in this trial. The combination of RAM plus IRI has anti-cancer activity and manageable safety profile in second-line treatment for patients with AGC. Clinical trial information: jRCTs011180029.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Tao Sun ◽  
Yanxia Shi ◽  
Jiuwei Cui ◽  
Yongmei Yin ◽  
Quchang Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

1087 Background: Breast cancer is the most common cancer among women, with up to 37% of patients (pts) harboring germline BRCA1/2 mutations (g BRCA1/2m) that appear to be sensitive to poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) inhibition. Pamiparib is an orally administered selective PARP1/2 inhibitor that has the potential to cross the blood-brain barrier. This study evaluated the efficacy and safety of pamiparib in pts with locally advanced/metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious g BRCA1/2m, who received ≤ 2 prior lines of chemotherapy. Methods: In this open-label, phase 2, multi-center study in China (NCT03575065), pts with locally advanced/metastatic HER2- breast cancer with deleterious or suspected deleterious g BRCA1/2m triple negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+ cohort) were enrolled. Pts received pamiparib 60 mg orally twice daily in 28-day cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and progression free survival (PFS) by IRC, overall survival (OS), safety and tolerability. Results: 88 pts were enrolled (median age 45.5 years), 76 pts (TNBC cohort n = 55; HR+ cohort n = 21) had measurable disease at baseline per IRC. 60 pts (68.2%) received 1 or 2 prior lines of chemotherapy; 42 pts (47.7%) were treated with platinum previously. Median follow-up was 13.77 months (TNBC cohort, 10.87 months; HR+ cohort, 18.45 months). In the TNBC cohort: confirmed ORR was 38.2% (95% CI: 25.4–52.3); median DOR (mDOR) was 6.97 months (95% CI: 3.94–not estimable[NE]); median PFS (mPFS) was 5.49 months (95% CI: 3.65–7.33); median OS (mOS) was 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR was 61.9% (95% CI: 38.4–81.9); mDOR was 7.49 months (95% CI: 5.55–14.75); mPFS was 9.20 months (95% CI: 7.39–11.93); mOS was not reached (NR; 95% CI 18.10–NE). ≥ Grade 3 treatment emergent adverse events (TEAEs) occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuations due to TEAEs occurred for 2 pts (2.3%). Conclusions: Pamiparib showed a promising response in pts with locally advanced/metastatic HER2- breast cancer with a g BRCA1/2m. The safety profile of pamiparib was considered acceptable and was generally consistent with therapies in the same class. Clinical trial information: NCT03575065 .[Table: see text]

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

2020 ◽  
Author(s):  
Ke Cheng ◽  
Yu-Wen Zhou ◽  
Ye Chen ◽  
Zhi-Ping Li ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Free Survival ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

Abstract Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

scholarly journals Efficacy and Safety of CAP7.1 as Second-Line Treatment for Advanced Biliary Tract Cancers: Data from a Randomised Phase II Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3149
Author(s):  
Ulrich-Frank Pape ◽  
Stefan Kasper ◽  
Johannes Meiler ◽  
Marianne Sinn ◽  
Arndt Vogel ◽  
...  
Keyword(s):  
Disease Progression ◽  
Biliary Tract ◽  
Phase Ii ◽  
Topoisomerase Ii ◽  
Clinical Investigation ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
Efficacy And Safety ◽  
Biliary Tract Cancers

CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2; iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%; treatment difference: 30%, 95%CI −18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31; 95%CI 0.11, 0.86; p = 0.009; FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.

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