Phase II prospective open label study of neoadjuvant pertuzumab, trastuzumab, and nab-paclitaxel in patients with HER-2 positive advanced breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 583-583
Author(s):  
Sayeh Moazami Lavasani ◽  
Susan Elaine Yost ◽  
Paul Henry Frankel ◽  
Christopher Ruel ◽  
Mireya Murga ◽  
...  
Keyword(s):  
Menopausal Status ◽  
Locally Advanced ◽  
Patient Characteristics ◽  
Her2 Overexpression ◽  
Loading Dose ◽  
Breast Cancers ◽  
Open Label ◽  
Median Treatment ◽  
Prior Surgery ◽  
Grade 3

583 Background: HER2 overexpression occurs in 20-25% of breast cancers (BC) and is associated with poor prognosis. The addition of trastuzumab (trast) to chemotherapy significantly improves disease-free (DFS) and overall survival (OS) in the adjuvant setting. Pertuzumab (pert) inhibits ligand-activated signaling and in combination with trast has synergistic inhibition of BC cells overexpressing HER2. In the neoadjuvant therapy (NT) setting, the combination of trast, pert, and docetaxel can improve the pCR rate. PCR may predict for improved DFS and OS. De-escalation with weekly paclitaxel combined with trast and pert appeared to be safe and efficacious but requires steroid premedication, whereas nab-paclitaxel (nab) does not require steroid premedication. To decrease treatment-associated toxicity in patients with HER2+ BC, we utilized a non-anthracycline regimen with pert, trast, and nab as NT. The objectives of this study were to evaluate the safety and efficacy of pert added to trast and nab in HER2+ locally advanced BC (LABC) to determine the pCR, as well as DFS and OS. Methods: A total of 45 patients with biopsy-confirmed HER2+ LABC or inflammatory BC were enrolled from 2013-2017, and were treated with 6 cycles of neoadjuvant pert (840 mg loading dose, then 420 mg IV day 1 every 21 days), weekly trast (4 mg/kg loading dose, then 2 mg/kg), and weekly nab (100 mg/m2 IV). Patient characteristics, including age, race, menopausal status, grade, stage, and prior surgery and radiation were recorded. Median treatment cycles determined, and events (AE) were identified for each arm. PCR rate, DFS and OS were calculated. Results: Median age was 56 (31-78) years. 1/45 (2%) was stage I, 30/45 (67%) were stage II, 14/45 (31%) were stage III. pCR rate was 29/45 (64.4%). The initial primary tumor size was similar in pCR and non-pCR patients (mean 4.1 cm vs. 3.2 cm, respectively). Median follow-up was 36.1 months (95% CI [27.1, 41.8]). Median treatment cycles completed was 6 (1-6). A total of 4/45 (9%) patients had >1 cycle delayed, and 32/45 (71%) patients had >1 cycle modified. For the patients achieving pCR, the DFS (95% CI) at 3 years was 85.9% (66.7%, 94.4%) and for those without pCR, it was 87.5% (58.6%, 96.7%). OS was not reached (95% CI [NR, NR]). Grade 3 AEs (> 2 patients) included 7/45 (16%) of patients with hypertension; 4/45 (9%) with anemia; and 2/45 (4%) with diarrhea, ALT, fatigue, or rash. Conclusions: This anthracycline-free regimen which included nab achieved great pCR rate of 64.4% in HER2+ BC patients with fewer treatment-related toxicities. The pCR rate is comparable with docetaxel, carboplatin, trast, and pert (TCHP) therapy in NT setting, but without the treatment-associated toxicities. This suggests we may be able to safely avoid anthracyclines and carboplatin for NT in HER2+ BC patients. The improved pCR did not translate into DFS benefit. Clinical trial information: NCT01730833.

281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A307-A307
Author(s):  
Gabriella Galffy ◽  
Iwona Lugowska ◽  
Elena Poddubskaya ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Maintenance Treatment ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Open Label Phase ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11550-e11550
Author(s):  
Stephen Tiley ◽  
Rachel Elizabeth Raab ◽  
Lisa Sheri Bellin ◽  
Jan H. Wong ◽  
Jackie Unger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Breast Cancers ◽  
Grade 3

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.

Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
Noah M. Hahn ◽  
Thomas Powles ◽  
Christophe Massard ◽  
Hendrik-Tobias Arkenau ◽  
Terence W. Friedlander ◽  
...  
Keyword(s):  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Anticancer Therapy ◽  
Clinical Activity ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

4525 Background: Anti-PD-L1 immunotherapy shows promising clinical activity in UC. We report a planned update of the safety and efficacy of durvalumab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. Methods: Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. Primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review (RECIST v1.1). Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Tumor PD-L1 expression was assessed by Ventana SP263 assay (PD-L1 high = ≥25% PD-L1 expression on tumor or immune cells). Results: As of Oct 24, 2016 (data cutoff [DCO]), 191 pts had received treatment. Median follow-up was 5.78 mo (range, 0.4–25.9). All pts had Stage 4 disease and 99.5% had prior anticancer therapy (95.3% post-platinum). As of DCO, ORR was 17.8% (34/191), including 7 CRs, with responses observed regardless of PD-L1 status (Table). Responses occurred early (median time to response, 1.41 mo) and were durable (median DoR not reached [NR]). Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively; the 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%). Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated (im)AEs occurred in 4 pts; 2 pts discontinued due to imAEs (acute kidney injury and autoimmune hepatitis). Conclusions: Durvalumab 10 mg/kg Q2W shows favorable clinical activity and an excellent safety profile in locally advanced/metastatic UC pts. Table. Antitumor activity in UC pts, including second-line or greater (≥2L) post-platinum pts Clinical trial information: NCT01693562. [Table: see text]

A phase II study of efficacy and safety of RC48-ADC in patients with locally advanced or metastatic HER2-overexpressing gastric or gastroesophageal junction cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4560-4560 ◽  
Author(s):  
Zhi Peng ◽  
Tianshu Liu ◽  
Jia Wei ◽  
Airong Wang ◽  
Yifu He ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Her2 Overexpression ◽  
Efficacy And Safety ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Microtubule Inhibitor ◽  
Eligibility Criteria

4560 Background: RC48-ADC is an antibody-drug conjugate (ADC) drug comprised of a novel humanized anti-HER2 IgG1, a linker, and a microtubule inhibitor, MMAE. The MoA included inhibition of HER2 signal pathway and cytotoxicity of MMAE. RC48-ADC has demonstrated promising anti-tumor activity in pre-clinical and early clinical studies. The current study is designed to evaluate the efficacy and safety of RC48-ADC in heavily treated patients with HER2-overexpressing (IHC 2+ or 3+) gastric or gastro-esophageal junction cancers. Methods: This is an open-label, multicenter, single-arm, phase II study. Eligibility criteria include: histologically confirmed gastric or gastro-esophageal junction cancers, HER2-overexpression (IHC 2+ or 3+), ECOG PS 0-1, post-to ≥2 prior systemic treatment. The patients received RC48-ADC, 2.5 mg/kg, q2w until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was ORR. PFS, OS, and safety were also evaluated. Results: Patient enrollment started in July 2017, and completed in November 2019. By the data cut-off date on 17-Dec-2019, 127 patients were enrolled. The median age was 58 years. At baseline, 59 patients (46.5%) had received ≥ 3 lines prior treatment. For the overall 127 patients, the investigator-assessed confirmed ORR was 18.1% (95% CI: 11.8%, 25.9%). Sub-group ORR was 19.4% and 16.9% for the patients post to 2 lines and ≥ 3 lines, respectively. For the 111 patients who were monitored for ≥ 2 cycles of efficacy assessments (i.e. 12 weeks), the ORR was 20.7% (95% CI: 13.6%, 29.5%). For the 127 patients, the mPFS was 3.8 months (95% CI: 2.7, 4.0, 89 events [70.1%]) and the mOS was 7.6 months (95% CI: 6.6, 9.2, 52 events [40.9%]). The most commonly reported treatment-related AEs were leukopenia (52.0%), alopecia (51.2%), neutropenia (48.0%), and fatigue (42.5%). Conclusions: RC48-ADC demonstrated a clinically meaningful response and survival benefit in the heavily treated patients with HER2-overexpressing gastric or gastro-esophageal junction cancers. The safety profile was in line with the previously reported data of RC48-ADC. RC48-ADC showed positive benefit/risk ratio for the target population. Clinical trial information: NCT03556345 .

FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
David I. Quinn ◽  
Daniel Peter Petrylak ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Activating Mutations ◽  
Stage Iv Disease ◽  
Dna Alterations ◽  
Grade 3 ◽  
Muscle Invasive

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

scholarly journals A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

2017 ◽  
Vol 7 (2) ◽  
pp. 28
Author(s):  
Gregory A. Vidal ◽  
Namratha Vontela ◽  
Mary Chen ◽  
Julie M. Ryder ◽  
Struti Sheth ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Breast Conservation ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Skin Reactions ◽  
Grade 3

Background: The use of HER2 targeting therapy has revolutionized the treatment of HER2 positive breast cancers. Here, we investigate whether a sequential approach to dual HER2 blockade of lapatinib followed by trastuzumab will result in improved clinical outcomes.Methods: This was a single institution, open label, single arm, phase II trial in women with HER2 positive breast cancer. Volunteers were treated with sequential neoadjuvant doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) for 4 cycles followed by docetaxel (100 mg/m2) concurrent with lapatinib (1,250 mg) (TL) daily for 21 days for four cycles before definitive surgery. The primary end point was pathologic complete response (pCR).Results: The study accrued only 21 of the 71 planned patients from 2/28/2007 to 5/25/2010. All patients (100%) experienced down staging. The pCR rate was 41% (7/18). 11 patients had tumor size of T3 or greater, 3 of which experienced pCR and only 1 underwent breast conservation (lumpectomy). The most common hematologic AE (all grades) was anemia 17/21 (81%). There were no incidences of grade 3 or 4 anemia. 10 of 21 (48%) patients experience a non-hematologic grade 3 AE. The most common non-hematologic AEs (all grades) were irregular menses 20/21 (95%) and hand-foot-skin reactions 20/21 (95%). No increase cardiac abnormalities were noted. The DFS at data cut off was 87.5%.Conclusion: The provocative pCR and DFS results in this high risk locally advanced patient population should be viewed with caution given results of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation study (ALTTO) clinical trial.

scholarly journals Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hanna Huebner ◽  
Christian M. Kurbacher ◽  
Geoffrey Kuesters ◽  
Andreas D. Hartkopf ◽  
Michael P. Lux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Menopausal Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Patient Characteristics ◽  
Breast Cancer Patients ◽  
Patient Identification ◽  
Eligibility Criteria

Abstract Background Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. Methods Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. Results Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. Conclusion Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. Trial registration Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Ezra E. W. Cohen ◽  
Theodore Karrison ◽  
Masha Kocherginsky ◽  
Chao H Huang ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
High Survival ◽  
Open Label ◽  
Free Survival ◽  
Prior Therapy ◽  
Distant Failure ◽  
Grade 3

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]

Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 256-256 ◽  
Author(s):  
Edward Samuel James ◽  
Xiaopan Yao ◽  
Xiangyu Cong ◽  
Stacey Stein ◽  
Kristin Kaley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Historical Data ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Sensory Neuropathy ◽  
Open Label ◽  
Grade 3 ◽  
Ecog Ps

256 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, we are conducting a prospective phase II open label study to evaluate the efficacy & tolerability of mFOLFIRINOX in pts with advanced pancreatic cancer (PC). Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX with 25% dose reductions of irinotecan & bolus 5-FU given every two wks until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. FDG-PET scans were obtained at baseline & after 2 cycles. CAT scans were obtained after every 4 cycles. Toxicities & response rate (RR) were compared to historical data reported by Conroy. Results: 53 pts with ECOG PS ≤1 have been enrolled to date between 11/11 and 08/13, Pt characteristics: LAPC 22; MPC 31; median age 62 yrs (range 46-86); male 30. Median # of cycles was 8 (range 1-21). Grade 3/4 toxicities were: anemia, febrile neutropenia (FN) & peripheral sensory neuropathy (PSN) – 3.8% each; ALT increased & thromboembolism – 5.7% each; diarrhea 7.5%; fatigue 11.3%; neutropenia 17%; thrombopenia 11.3% & vomiting 1.9%. Anemia ( p< 0.04), FN (p<0.04), PSN (p<0.04) and vomiting (p<0.02) were significantly decreased compared to historical data (Conroy). Response by RECIST (CR+PR) in 26 evaluable pts with MPC was 29% (0 CR, 9 PR, 14 SD, 3 PD) & similar to historical data (31.6%; p 0.85). 6/13 evaluable pts with LAPC underwent resection (46%).13/36 pts evaluable for PET response had a >50% decrease in SUV(max)(36%). Evaluation for OS & PFS is ongoing. Conclusions: Findings from our interim analysis suggests that mFOLFIRINOX, given along with prophylactic pegfilgrastim is associated with a similar RR and improved tolerability compared to full dose FOLFIRINOX in advanced PC. In pts with LAPC, neoadjuvant FOLFIRINOX appears to have substantial activity with 46% of evaluable pts undergoing resection. Accrual will continue to reach a goal of 70 pts. Clinical trial information: NCT01523457.

Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 366-366
Author(s):  
Naoya Ikeda ◽  
Takahiro Akahori ◽  
Sohei Satoi ◽  
Hiroaki Yanagimoto ◽  
Minako Nagai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Impact ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Conversion Surgery ◽  
Open Label ◽  
Grade 3 ◽  
Medical University

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

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