scholarly journals Sunitinib – vom Paradigmenwechsel zu einem Therapiestandard beim metastasierten Nierenzellkarzinom (mRCC)

2010 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 2-4
Author(s):  
Lothar Bergmann
Keyword(s):  
Interferon Alpha ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Iii ◽  
Expanded Access ◽  
Zielgerichtete Substanzen

Zielgerichtete Substanzen haben in der Behandlung des metastasierten Nierenzellkarzinoms (mRCC) zu einem Paradigmenwechsel gefÜhrt. Der Multi-Kinase-Inhibitor Sunitinib konnte sich innerhalb kurzer Zeit als ein neuer Standard in der Erstlinientherapie etablieren. In einem umfassenden Studienprogramm wurde Sunitinib ausgehend von Phase-II-Studien in der Zweitlinientherapie Über eine Phase-III-Studie zur Erstlinientherapie bis hin zum breiten Einsatz in der klinischen Praxis systematisch entwickelt. Die Prognose fÜr Patienten mit mRCC hat sich durch die EinfÜhrung des Multi-Kinase-Hemmers deutlich verbessert: GegenÜber Interferon-alpha wurde mit Sunitinib eine Verdopplung des progressionsfreien Überlebens und eine Vervierfachung der Ansprechrate erreicht. Die hohe Wirksamkeit Übersetzte sich auch in das mediane GesamtÜberleben von Über 2 Jahren im Sunitinib-Arm der Studie. Zusammen mit den konsistenten Ergebnissen des internationalen Sunitinib-Expanded-Access-Programms verfÜgt die Substanz Über eine breite Evidenzbasis und umfassende praktische Erfahrung fÜr den Einsatz in allen Patientenpopulationen. Dies spiegelt sich auch in den Empfehlungen nationaler und internationaler Fachgesellschaften wider. In Deutschland ist Sunitinib die am hÄufigsten eingesetzte Substanz beim mRCC.

Witnessing a New Era? – The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2010 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signalling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomised Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2012 ◽  
Vol 08 (02) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
B. Escudier ◽  
C. Szczylik ◽  
T. Demkow ◽  
M. Staehler ◽  
F. Rolland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Prognostic Score ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]

Phase II evaluation of cisplatin plus cetuximab in the treatment of recurrent and persistent cancers of the cervix: A limited access phase II study of the Gynecologic Oncology Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5521-5521
Author(s):  
J. H. Farley ◽  
M. Sill ◽  
J. L. Walker ◽  
R. J. Schilder ◽  
J. T. Thigpen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Gynecologic Oncology ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Poor Prognostic Factor

5521 Background: A majority of cervical cancer patients overexpress epidermal growth factor receptor (EGFR), which is a poor prognostic factor. Cetuximab (C225) is a murine monoclonal antibody that binds to EGFR and competes with ligand binding and tyrosine kinase activation.Given the evidence of activity in squamous carcinomas of the head and neck, the purpose of this study was to evaluate the safety and efficacy of cisplatin and cetuximab chemotherapy. Methods: Women with advanced, persistent, or recurrent carcinoma of the cervix not amenable to cure were eligible for this study. Only prior chemotherapy (CT) administered in conjunction with primary radiation as a radiosensitizer was allowed. Women could not have received prior anti-EGFR antibody therapy or therapy with a tyrosine kinase inhibitor that targets the EGFR pathway. All women had measurable disease and a GOG performance status ≤ 2. The women received cisplatin at 30 mg/m2 days 1 and 8. The first dose of C225 was given at 400 mg/m2. All subsequent doses of C225 were given at 250 mg/m2. C225 was given on days 1, 8, and 15. Each cycle was 21 days. Adverse events were assessed with CTCAE v 3.0. Primary measure of clinical efficacy was the frequency of tumor response. The study was stratified by prior CT. The design required at least 16 responses in a sample of 40 with prior CT and 29 without prior CT before the regimen was considered for phase III testing. Results: Between September 2004 and March 2008, 76 patients were entered onto the study. Of these, 69 were eligible and evaluable. Three patients were on study at the time of the analysis. 56 (81%) patients had received prior radiation. 40 (58%) patients previously received prior CT. There were 8 (12%) responses. The response rate was 8% among patients with prior CT, and 17% among CT naïve patients. One woman had grade 4 anemia. The most common grade 3 toxicities were metabolic (14), dermatologic (8), fatigue (6), and gastrointestinal (6). Conclusions: The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy. Stratification of patients based upon K-ras mutation and/or EGFR status may select a group for which this regimen is most effective. No significant financial relationships to disclose.

ASPIRATION: Phase II study of continued erlotinib beyond RECIST progression in Asian patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7614-TPS7614 ◽  
Author(s):  
Keunchil Park ◽  
Chun-Ming Tsai ◽  
Myung-ju Ahn ◽  
Chong-Jen Yu ◽  
Sang-We Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
Life Threatening ◽  
Pre Treatment

TPS7614 Background: First-line erlotinib (an EGFR tyrosine-kinase inhibitor) significantly increased progression-free survival (PFS) vs chemotherapy in phase III trials of pts with EGFR mutation-positive NSCLC. Discontinuation of erlotinib on RECIST disease progression (PD) may lead to rapid disease flare-up; continued erlotinib beyond RECIST PD may extend clinical benefit by slowing progression of this life-threatening disease. We describe ASPIRATION, a large, Asian, multicenter, single-arm, open-label, phase II trial (NCT01310036), which will increase understanding of first-line erlotinib and erlotinib continuation beyond RECIST PD in pts with EGFR-mutated NSCLC. Methods: Pts (n=204) ≥18 yrs with stage IV/recurrent NSCLC, ≥1 measurable lesion (≥10mm), ECOG performance status (PS) 0-2 and positive EGFR mutation status established by local pathology laboratory (that underwent voluntarily QA/QC) are eligible. All pts receive erlotinib 150mg/day. Tumor response is evaluated using RECIST (v1.1). The primary endpoint is PFS. At investigator's discretion, pts may continue on erlotinib beyond RECIST PD, e.g. if they have slow PD (>6 months of partial response/stable disease), asymptomatic minimal PD, or new brain metastasis controlled locally. Pts should not continue erlotinib if they have extracranial PD with symptoms; rapid PD and/or worsening of PS; or life-threatening complications. Pts continuing erlotinib who present with second RECIST PD will discontinue. Secondary endpoints include objective response rate, disease control rate, overall survival, and safety. For the exploratory biomarker study, pre-treatment tumor tissue blocks are collected; remaining tissue (after EGFR mutation testing for eligibility) will be analyzed centrally to study the association of biomarkers and clinical outcomes. Pre-treatment and post-treatment plasma and serum samples will be obtained at various time points for biomarker assays, including EGFR mutations and other candidate NSCLC biomarkers. Recruitment began in Apr 2011; the estimated final data collection for the primary endpoint is Dec 2014.

Multicenter phase II clinical trial of everolimus in Japanese patients with unresectable or metastatic renal cell carcinoma (mRCC) after failure of treatment with first-line tyrosine kinase inhibitor (TKI) therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 455-455
Author(s):  
Seiichiro Ozono ◽  
Masafumi Oyama ◽  
Masahiro Nozawa ◽  
Kiyohide Fujimoto ◽  
Ken Kishida ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Line Setting

455 Background: Everolimus has shown the efficacy and the safety in the phase III trial (RECORD-1) in patients with mRCC after failure of Vascular Endothelial Growth Factor Receptor-TKI. However, 26% of patients received two TKIs (sunitinib and sorafenib) as previous therapy in RECORD-1. In addition, as pre-treatment before TKI, 65% of patients received cytokine therapy and 13% of patients received chemotherapy. Therefore, there is still no clear evidence of everolimus as second line setting after failure of 1st-line TKI therapy. Methods: This study is an open-label, multi-center, single-arm, phase II trial. Primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, objective response rate, time-to-treatment-failure, safety and quality of life (EORTC QLQ-C30, FKSI-DRS, EQ-5D). Key eligibility criteria are RCC with clear cell component, patients who received one TKI as first line therapy, patients who did not receive cytokine and chemotherapy and ECOG performance status 0-1. Results: 57 patients were enrolled from 02/11 to 12/12. Median age was 63 years, common sites of metastasis were lung (32.7%) and bone (12.2%), 79.6% had previous nephrectomy, previous TKI therapy were sunitinib (69.4%), sorafenib (22.4%) and axitinib (8.2%). Median PFS was 4.4 months (95% confidence interval: 3.7-6.0). 8.2% had partial response and 57.1% had stable disease according to RECIST v.1.0. The incidence of adverse events (AEs) of all grades was 95.9%. Major AEs were stomatitis (49.0%), hypertriglyceridemia (26.5%) and hypercholesterolemia (24.5%). Serious AEs were stomatitis (10.2%), interstitial lung disease (6.1%) and rash (6.1%). There were no treatment related deaths. All QOL scores were not changed at 2 months, while dyspnea and global health scores of EORTC QLQ-C30 and FKSI-DRS score were worsened at 4 months. Conclusions: This study is a first report of everolimus as second line setting after failure of 1st-line TKI. Further study and long-term follow-up would be warranted. Clinical trial information: UMIN000004742.

INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG), first results.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
Nick Pavlakis ◽  
Katrin Marie Sjoquist ◽  
Eric Tsobanis ◽  
Andrew Martin ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Prognostic Indicators ◽  
Controlled Study ◽  
Primary Analysis ◽  
Double Blind

9 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has limited options following failure of first or second line chemotherapy (CT). Regorafenib (REG) is an oral multi-kinase inhibitor of kinases involved in angiogenesis, tumor microenvironment, and oncogenesis. This study examined whether REG has sufficient activity and safety for further evaluation. Methods: International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) randomised phase II trial with 2:1 randomisation and stratification by: (1) Lines of prior CT for advanced disease (1 vs. 2) and (2) Region. Eligible patients received best supportive care plus 160mg REG or matching PBO orally on days 1-21 each 28-day cycle until disease progression or prohibitive adverse events. Primary endpoint was progression free survival (PFS) in the REG arm, assuming median 8 weeks (wks) in PBO arm, aiming for 13.2 wks with REG to be of interest. Results: From Nov 2012 to Feb 2014, 152 patients were enrolled, 147 evaluable [pre-specified primary analysis population]: (REG n=97: PBO n=50); well matched for key baseline prognostic indicators; male:female (118:29); primary location: OG Junction (56), stomach (85); lines of prior therapy: 1 (63), 2 (84); ECOG 0 (62): 1 (85). Time on treatment: Median: 7.9 (REG) v 4 (PBO) wks. In the evaluable population median PFS was 11.1 wks (95% CI: 7.7 - 12.3) (REG) and 3.9 wks (95% CI: 3.7 - 4.0) (PBO), log-rank p <0.0001; HR 0.41 (95% CI: 0.28 to 0.59). PFS results were maintained for secondary analysis including all randomized patients (n = 152). REG was well tolerated, with the spectrum of toxicity in keeping with previous reports. Conclusions: PFS was clearly significantly longer with REG than PBO, though PBO PFS was less than anticipated. The pre-specified exploratory comparisons provide compelling evidence that REG has sufficient activity with acceptable tolerability in refractory AOGC to warrant phase III evaluation. Mature OS results will be presented at the meeting. Clinical trial information: 12612000239864.

SAVANNAH: A Phase II trial of osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-driven (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC), following disease progression on osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9119-TPS9119 ◽  
Author(s):  
Geoffrey R. Oxnard ◽  
Mireille Cantarini ◽  
Paul Frewer ◽  
George Hawkins ◽  
Jane Peters ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Survival Duration ◽  
Common Mechanism ◽  
Egfr Mutant

TPS9119 Background: The toxicity profile of the third-generation EGFR-tyrosine kinase inhibitor (TKI) osimertinib makes it an attractive backbone for combination with other targeted agents, possibly overcoming acquired resistance mechanisms. Combination with a MET-inhibitor is an intuitive approach as MET-amplification was identified as the most common mechanism of resistance to osimertinib in preliminary ctDNA data from the Phase III FLAURA (15% of pts) and AURA3 (19% of pts) studies. Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent and highly selective MET-TKI that had an acceptable safety profile when combined with osimertinib in the Phase Ib TATTON study, providing the basis for this Phase II SAVANNAH study (NCT03778229). Other mechanisms of acquired resistance to osimertinib, including secondary EGFR mutations (e.g. C797S), RAS/RAF activation, and oncogenic gene fusions, provide additional opportunities for developing osimertinib-based combinations. Methods: Eligible pts will have histologically/cytologically confirmed EGFR-mutant NSCLC, and MET+ disease by central FISH, central IHC, or local NGS (retrospectively confirmed by central FISH/IHC). Pts must have documented radiological progression following 1–3 lines of prior therapy (must include osimertinib). Pts will receive osimertinib 80 mg plus weight-based dosing with savolitinib 300 or 600 mg PO QD, in 28-day cycles. The primary objective is efficacy (RECIST 1.1) by overall response rate (ORR) in pts who are MET+ by central FISH. Secondary endpoints include: ORR ( MET+ by central IHC and all pts); progression-free survival, overall survival, duration of response, percent change in tumor size, HRQoL, and EGFR mutation ctDNA clearance ( MET+ by central FISH, central IHC, and all pts); safety, and pharmacokinetics (all pts). Based on the TATTON study, we anticipate enrolling ~172 MET+ pts to include ≥117 pts with MET+ disease by central FISH. Enrolment began in Q1 2019. Ongoing development of complementary trials targeting other osimertinib resistance mechanisms will also be discussed. Clinical trial information: NCT03778229.

Pyrotinib plus capecitabine for HER2-positive metastatic breast cancer patients with brain metastases (PERMEATE): A multicenter, single-arm phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1037-1037
Author(s):  
Min Yan ◽  
Quchang Ouyang ◽  
Tao Sun ◽  
Limin Niu ◽  
Jin Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Positive

1037 Background: HER2-positive metastatic breast cancer (BC) has a high risk of brain metastases (BM), leading to poor survival. Small molecule tyrosine kinase inhibitor (TKI) with enhanced penetrability to the blood brain barrier combined with capecitabine have demonstrated promising clinical outcomes in HER2-positive metastatic BC patients with untreated (such as lapatinib) or previously treated (such as neratinib) BM. The randomized phase III PHOEBE trial has proved better efficacy of pyrotinib, an irreversible pan-HER receptor TKI, versus lapatinib when in combination with capecitabine in HER2-positive local relapsed or metastatic BC. This study was conducted to investigate the efficacy and safety of pyrotinib plus capecitabine in HER2-positive metastatic BC patients with BM. Methods: In this multicenter phase II trial (NCT03691051), eligible patients received pyrotinib 400 mg orally once daily without breaks and capecitabine 1000 mg/m2 orally twice daily for 14 days followed by 7 days off. Treatment was continued until disease progression or intolerable toxicity. Prior HER2 TKIs were not allowed. Cohort A included patients with radiotherapy-naive BM, and cohort B included those with progressive BM after whole brain radiotherapy or stereotactic conformal radiotherapy. The primary endpoint was confirmed central nervous system (CNS) objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Results: Between January 2018 and July 2020, a total of 78 female patients were included (Table). For cohort A (n = 59), the CNS ORR was 74.6% (95%CI: 61.6%-85.0%). For cohort B (n = 19), the CNS ORR was 42.1% (95%CI: 20.3%-66.5%). By the cutoff date on 25 January 2021, the median progression-free survival was 12.1 months (95%CI: 9.0-14.7) in cohort A and 5.6 months (95%CI: 3.4-10.7) in cohort B. The most common grade ≥3 adverse events were diarrhea (23.1% [18/78]), neutrophil count decreased (12.8% [10/78]), white blood cell count decreased (12.8% [10/78]), anemia (9.0% [7/78]), hand-foot syndrome (7.7% [6/78]), hypertriglyceridemia (6.4% [5/78]), and hypokalemia (5.1% [4/78]). Conclusions: Pyrotinib plus capecitabine resulted as an effective and safe treatment for HER2-positive BC patients with radiotherapy-naive BM, but the efficacy was modest in those with radiotherapy-treated BM. Clinical trial information: NCT03691051 .[Table: see text]

Sunitinib-related thyroid dysfunction: A single-center retrospective and prospective evaluation

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3092-3092 ◽  
Author(s):  
P. Schoeffski ◽  
P. Wolter ◽  
U. Himpe ◽  
S. S. Dychter ◽  
C. Baum ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Prospective Cohort ◽  
Thyroid Dysfunction ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Phase Iii ◽  
Hormone Substitution ◽  
Data Set ◽  
Phase Iii Trial ◽  
Expanded Access

3092 Background: Sunitinib is a multi-target tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity mediated by signal blockade of VEGFR1/2, KIT, PDGFRα/β, and FLT-3. Phase II/III trials have demonstrated efficacy of the oral agent in Imatinib-resistant GIST and advanced renal cell cancer (RCC). We observed several cases of thyroid dysfunction in GIST during treatment with sunitinib suggesting that the drug may be associated with hypothyroidism. We therefore assessed the incidence and severity of thyroid dysfunction in cancer patients treated with sunitinib. Methods: Thyroid function (serum TSH, T3 and free thyroxin index) and thyroid antibodies (anti-TPO, -Tg and TSH-R-Ab) were evaluated retrospectively in a cohort of patients with GIST in a Phase III trial and in an expanded access program (1st part of the investigation) and in a prospective cohort of RCC and GIST patients treated in the framework of expanded access programs (2nd part). Sunitinib was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off. Thyroid parameters were assessed on days 1 and 28 of each treatment cycle in the prospective cohort. We report here the first TSH results, the full data set will be available at ASCO. Results: We identified a total of 46 patients who received sunitinib, and 33 of these patients were evaluable for thyroid function. 14 patients were analyzed retrospectively (all GIST), 19 patients prospectively (8 GIST, 11 RCC). 7 of these 19 patients (37%) showed an elevated TSH (>5 mIU/L) during treatment. In the retrospective analysis of 14 patients with a median treatment duration of 44 weeks, 8 patients (57%) had developed hypothyroidism. All patients with GIST in randomized Phase III trial remaining under active treatment with sunitinib for 58–80 weeks show an increased TSH (up to 83 mIU/L) during the course of treatment, requiring hormone substitution. In a cohort of 11 patients with RCC, after 6 weeks of treatment, 3 patients already have an increased TSH. Conclusions: Sunitinib is associated with a high incidence of thyroid dysfunction which requires further study. The mechanism by which Sunitinib induces thyroid dysfunction is yet unclear. No significant financial relationships to disclose.

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