scholarly journals A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer

2021 ◽  
Author(s):  
Megumi Kai ◽  
Angela N. Marx ◽  
Diane D. Liu ◽  
Yu Shen ◽  
James M. Reuben ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Locoregional Recurrence ◽  
Injection Site Reaction ◽  
Progression Free Survival ◽  
Median Number ◽  
Talimogene Laherparepvec ◽  
Best Response ◽  
Registration Number ◽  
Number Of Cycles

Abstract Purpose: Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer.Methods: Patients had to have cutaneous, subcutaneous, or nodal tumors injectable with T-VEC. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥3). Local lesions were photographed before each cycle.Results: Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n=7, 78%).Conclusion: None of the patients was able to complete the planned 10 cycles due to the disease progression. Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02658812; registered [January 14, 2016]

scholarly journals A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megumi Kai ◽  
Angela N. Marx ◽  
Diane D. Liu ◽  
Yu Shen ◽  
Hui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Injection Site Reaction ◽  
Progression Free Survival ◽  
Median Number ◽  
Talimogene Laherparepvec ◽  
Distant Disease ◽  
Best Response ◽  
Common Grade ◽  
Number Of Cycles

AbstractTalimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

scholarly journals Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Sun Lee ◽  
Susan E. Yost ◽  
Suzette Blanchard ◽  
Daniel Schmolze ◽  
Hongwei Holly Yin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Median Number ◽  
Primary Objective ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. Methods The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). Results Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0–8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). Conclusion Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. Trial registration ClinicalTrials.gov, NCT02120469. Registered 18 April 2014

Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A randomized phase III trial of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study (HECTOR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Jalid Sehouli ◽  
Werner Meier ◽  
Pauline Wimberger ◽  
Radoslav Chekerov ◽  
Antje Belau ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Platinum Sensitive ◽  
Best Response ◽  
Phase Iii Study ◽  
Number Of Cycles

5031 Background: We present the efficacy data from a phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m²/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Progression free survival at 1 year was defined as primary endpoint. Results: Median number of cycles was 6 (range 0-9) in both arms. Most patients preferred GC (78%) in the standard therapy arm.. Best Response (CR+PR) was 73.1% (95%CI) and 75.1% (95%CI) for the CA. Median follow-up was 18 (0-52) months for TC and 20 (0-48) months for standard therapy. TC failed to show any advantage regarding 1-yr.-PFS or OAS. Conclusions: The combination of topotecan plus carboplatin failed to improve PFS or OAS in platinum sensitive relapsed ovarian cancer. In addition, carboplatin plus gemcitabine was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities compared to paclitaxel-carboplatin. [Table: see text]

Outcomes of advanced stage non-small cell lung cancer (NSCLC) patients reexposed to platinum-based chemotherapy upon progression

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17136-17136
Author(s):  
P. H. Souza ◽  
A. N. Rodrigues ◽  
R. Dienstmann ◽  
I. A. Small ◽  
W. Roriz ◽  
...  
Keyword(s):  
Disease Progression ◽  
Progression Free Survival ◽  
Median Number ◽  
Advanced Stage ◽  
Line Treatment ◽  
Consensus Definition ◽  
Platinum Based Chemotherapy ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Nsclc Patients

17136 Background: Platinum-based chemotherapy (PtCT) is the standard 1st-line treatment for advanced stage NSCLC patients. Nearly all patients (pts) that respond to 1st-line CT will relapse and some of them will be candidates for 2nd-line CT. There is no consensus definition of sensitive or resistant pts to PtCT and there are conflicting results about the relationship between response to prior PtCT and response to a 2nd-line reexposure. The aim of this study was to evaluate the outcomes of a subset of pts considered sensitive to platinum, who were reexposed to a PtCT regimen as 2nd-line CT. Methods: Based on a criterion of disease progression > 6 months of completing 1st-line as a hallmark platinum-sensitivity, pts were retrospectively selected. We reviewed the outcomes of 11 advanced NSCLC pts (stages IIIB or IV) treated between Jan 2000 and Jun 2005 at 1st-line with a PtCT (cisplatin or carboplatin combined to etoposide) and who upon progression were reexposed to a regimen of Carboplatin plus etoposide. Pts were evaluated for overall (OS) and progression-free survival (PFS) after 1st- and 2nd-line CT by Kaplan-Meyer method. Results: There were 6 women (54.5%) and 5 men (45.5%). Median age was 62 (range 49–78) and adenocarcinoma was the most prevalent histology (54.5%). At 1st-line CT, 6 patients (54.5%) were stage IIIB and ECOG PS 0/1 were 36.4 and 63.6%, respectively. The median number of cycles per patient was 6 (range 2–8) at 1st-line and 4 (range 2–4) at 2nd-line treatment. With a median follow-up of 29 months, there were 4 deaths (36.5%) with a median OS of 49 months (CI 95%; 29.38–68.62). The median PFS after first-line was 17 months (IC 95%; 13.87–20.13). To date, 7 pts have progressed after 2nd-line CT with a median PFS of 8 months (IC 95%; 5.92–10.09). Conclusions: This subset of pts with longer progression-free interval (> 6 months) after 1st-line PtCT seems to remain sensitive to platinum compounds upon disease progression. Despite the high proportion of stage III in our sample, based on the long DFS and OS observed, it seems that this population has a more favorable biology than the general population with NSCLC. Further studies, in particular pharmacogenetic analyses, are needed in order to better characterize and treat this population. No significant financial relationships to disclose.

Phase II study of oxaliplatin-based chemotherapy in patients with advanced gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14119-14119
Author(s):  
E. Vattemi ◽  
R. Pedersini ◽  
B. Kildani ◽  
J. Stocker ◽  
S. Baier ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Progression ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Median Number ◽  
Clinical Activity ◽  
Who Grade ◽  
Number Of Cycles

14119 Background: The aim of the study was to assess the toxicity and the clinical activity of oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks in patients with advanced gastric cancer. Methods: 26 patients with recurrent and/or metastatic gastric cancer were enrolled. They received oxaliplatin 85 mg/mq on day 1, FA 200 mg/mq as a 2 h infusion followed by bolus 5-FU 400 mg/mq repeated for 2 consecutive days (FOLFOX-4). Treatment was repeated every two weeks until disease progression or limiting toxicity. Results: Patients had a median age of 62 years (range, 74–40); 19 patients had a PS of 0–1. Twenty patients had a newly diagnosed metastatic disease and 6 patients had recurrent disease. The median number of sites involved was 2. Four patients had prior adjuvant chemotherapy with cisplatin, 5-FU and epirubicin. So far, 22 of 26 patients are evaluable. The mean number of cycles was 8.6 (range, 2–15). One complete response (4.5%) and 9 partial responses (41%) were observed for an overall response rate of 45%. Stable disease was seen in 8 patients (36%) and disease progression occurred in 4 patients (18%) Median progression free survival was 4.7 months and median overall survival was 9.8 months. No WHO grade IV toxicity occurred and the only grade III toxicity was peripheral neuropaty (10%). The most commonly reported hematologic event was grade II neutropenia (20%) and trombocytopenia (15%). Conclusions: FOLFOX-4 regimen shows good efficacy and accetable safety profile in advanced gastric patients. No significant financial relationships to disclose.

Bevacizumab as maintenance therapy (mBev) in metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22149-e22149 ◽  
Author(s):  
Loredana Militello ◽  
Paolo Carli ◽  
Vincenzo Di Lauro ◽  
Simon Spazzapan ◽  
Simona Scalone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Objective Response ◽  
Median Number ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Number Of Cycles

e22149 Background: Preclinical models suggest that the anti-VEGF may improve the efficacy of anti-estrogen therapies in Hormonal Receptor positive (HR+) breast cancer, but there is lack of informations about the maintenance therapy with Bev (mBev) and Hormonal Therapy (HT). Methods: sixty-one pts with HER-2 negative MBC were treated, at our institution from 2007, with Bev+Taxanes (BT) as 1stline chemotherapy and with HT in HR+ pts as maintenance therapy. Primary endpoints were the evaluation of Progression Free Survival (PFS) and Overall Survival (OS). Secondary endpoint was the safety with HT in HR+ pts. Results: Hormonal status was positive in 52/61 (85%). Antracyclines were administered as adjuvant therapy in 26 pts (42%), antra+tax in 26 (42%) pts, no adjuvant therapy in 9 pts (14%). At the time of first relapse, median age was 50 y/o (range 33-72). First line HT was given to 12 pts. Metastatic sites were only bone in 20 pts (32%), visceral in 15 pts (25%), bone + visceral in 19 pts (31%), lymph nodes in 7 pts (11%). ECOG PS was 0 in 56 pts and 1 in 5. Median number of cycles of BT was 7 (1-14). All pts were evaluated for PFS and OS and 45 pts were evaluated for objective response: complete response (CR) was achieved in 5/45 pts (11%) (duration 12 months), partial response (PR) in 34/45 pts (75%) (duration 6-7 months), stable disease (SD) in 6/45 pts (14%) (6 months). After the assessment of the response, 34/61 pts received maintenance Bev (mBev); among this group, 24/34 pts with HR+ were also treated with HT until disease progression. The median number of cycles of mBev was 8 (1-42). Median PFS was 13.5 months (95%CI: 10.2-18.2) and median OS was 36 months (95%CI: 22-51). The BT regimen was well tolerated: 2 pts experienced cardiotoxicity with a reduction in left ventricular ejection fraction (LVEF); the most common side effects were hypertension (grade 1 in 11 pts e grade 2 in 16 pts), bleeding in 8 pts, proteinuria in 7 pts (grade 1 in 5 pts and grade 2 in 2 pts). Conclusions: Hormonalmaintenance and Bev can extend the overall benefit of therapy and it is well tolerated and associated with long-term clinical outcome. Our results are encouraging for prolonging Bev in association with HT as maintenance therapy until disease progression.

Deep proteomic analysis of plasma exosomes in patients with advanced, hormone receptor-positive breast cancer treated with palbociclib and tamoxifen.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
Xiuyuan Ma ◽  
Yu Gao ◽  
Gayatry Mohapatra ◽  
Louis Coleman ◽  
Yael Simons ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Hormone Receptor ◽  
Proteomic Analysis ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
First Line Therapy ◽  
Hormone Receptor Positive ◽  
Best Response ◽  
Extraction And Purification

1030 Background: Combining a CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) in advanced, hormone receptor (HR)-positive, HER2-negative breast cancer (BC) doubles median progression-free survival, but eventually drug resistance and disease progression occur. For most patients, the mechanism of resistance is unknown. Exosomes are membrane-bound extracellular vesicles that contain lipids, proteins, and nucleic acids, and are released from tumors as a form of intercellular communication. Exosomes can be recovered from plasma, and analysis of their cargo provides a dynamic read-out of biological pathways that are activated in cancer cells. Proteomic analysis of plasma exosomes may provide insight into mechanisms of resistance that emerge during treatment with CDK4/6i-ET. Methods: The Big Ten Cancer Research Consortium conducted a single arm, phase II trial of palbociclib plus tamoxifen as first line therapy for advanced, HR+/HER2- BC (NCT02668666). Whole blood was collected in Streck tubes from study participants (n = 49) at baseline, at disease progression, and at time points during study treatment. Plasma was separated and stored at -80C within 48 hours of collection. Exosomes were isolated from thawed plasma using commercially available kits and ultracentrifugation. Exosome extraction and purification was optimized for protein recovery. Purified exosomes were processed for proteomic analysis and labeled with TMT10 (tandem mass tag 10plex) and quantified with the QExactive HF mass spectrometer. Ultrasensitive mass spectrometry provided deep proteomic coverage of exosomal proteins and detected various post-translational modifications (PTM). Data were analyzed with a pipeline developed in our lab using an improved SEQUEST/ProLuCID database search engine and Percolator data filtering toolchain. Exosome protein expression was determined at baseline, at best response and at the time of progression. Results: With our ultrasensitive proteomic method, we detected more than 500 exosome proteins from as little as 100 ng of purified exosomes. A significant enrichment of exosome specific markers was observed when comparing patient samples with healthy donor samples. Enrichment of surface glycoproteins (e.g. CD44) was seen in BC patient samples, as in previous reports. Ultrasensitive proteomics also detected PTM including phosphorylation, methylation, oxidation, deamidation, and glycosylation. Differential proteomic and PTM profiles comparing samples collected from responding patients at baseline vs. at progression will be presented. Conclusions: Our innovative method provided an unparalleled portrait of the proteomic landscape of plasma exosomes during treatment with CDK4/6i-ET. This powerful approach may provide novel insights into mechanisms of resistance that emerge during treatment. This study was funded by Pfizer. Clinical trial information: NCT02668666 .

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Capecitabine monotherapy for patients with brain metastases from advanced breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1102-1102 ◽  
Author(s):  
D. R. Naskhletashvili ◽  
V. A. Gorbounova ◽  
M. B. Bychkov ◽  
G. E. Chmutin ◽  
V. B. Karakhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Advanced Breast ◽  
Ecog Performance Status ◽  
Prior Chemotherapy ◽  
Best Response ◽  
The Brain

1102 Background: To assess the efficacy of capecitabine monotherapy for patients with chemotherapy-pretreated advanced breast cancer with brain metastases. Methods: Patients with brain metastases from breast cancer whose disease had progressed on prior chemotherapy for advanced disease received oral capecitabine 1,000 mg/m2 bid on days 1–14 every 3 weeks until disease progression. Results: Between July 2007 and August 2008, 10 women were treated. Median age was 50 years (range 36–66 years). ECOG performance status was 1 in 7 patients and 2 in 3 patients. All had received prior chemotherapy: one line in five patients; two lines in four patients; three lines in one patient. Six patients had received prior endocrine therapy and three had received prior salvage radiotherapy to the brain. Two patients had metastases limited to the brain and the remaining eight also had extracranial metastases. All patients were assessable for response. Six achieved a partial response in the brain (CT/enhanced-contrast MRI), three showed disease stabilization, and one had disease progression as best response. Median duration of response was 4 months and median time to progression was 6 months. Seven patients are still alive and therefore median overall survival has not been reached. A total of 58 cycles of capecitabine were delivered. The most common toxicities (% of cycles) were neutropenia (G1/2 43.1%, G3/G4 8.6%), hand-foot syndrome (G1/2 25.9%, G3 8.6%), anemia (G1/2 29.3%, G3 1.7%), diarrhea (G1/2 20.6%, G3 5.2%), nausea/vomiting (G1/2 24.1%), stomatitis (G1/2 12%), thrombocytopenia (G1 8.6%), and fatigue (G1/2 6.9%). Conclusions: Our small study suggests that capecitabine has pronounced anticancer activity in patients with brain metastases from breast cancer with reasonable tolerability and easy administration as outpatient treatment. Further investigation is warranted. No significant financial relationships to disclose.

Phase II dose escalation study of sorafenib in patients with metastatic renal cell carcinoma (mRCC) who have had prior treatment with VEGFR-TKI antiangiogenic treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
A. P. Mancuso ◽  
E. Donato De Paola ◽  
A. Catalano ◽  
F. Calabrò ◽  
C. Messina ◽  
...  
Keyword(s):  
Standard Dose ◽  
Progression Free Survival ◽  
Median Number ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Prior Therapy ◽  
Hand Foot Syndrome ◽  
Tki Treatment ◽  
Number Of Cycles ◽  
Metastatic Sites

e16027 Background: Sorafenib is an orally active multikinase inhibitor (Raf kinase, VEGFR 1, 2, 3 and PDGFR inhibitor) for the treatment of advanced RCC. The purpose of this study was to assess the efficacy and toxicity of Sorafenib in mRCC patients (pts) previously treated with an anti-angiogenic VEGFR-TKI using escalating dose levels. Methods: Pts with mRCC, PS 0–2 and adequate organ function were eligible. Pts received Sorafenib 400 mg/BID/continuously in 4-wk cycles. Pts with no progressive disease (evaluated at 12 weeks) continued to receive Sorafenib at the standard dose, while progressive pts received an increasing dose (600 mg BID) with early disease restaging after 4 weeks. Pts who progressed at 600 mg BID were taken off study. Efficacy was assessed by RECIST criteria. Results: 18 pts were entered; baseline characteristics: PS 0–1: 94%; median age 62 years (41–82); nephrectomy: 100%; surgery for metastatic disease: 28%, clear-cell 78%, papillary-cell 16%, sarcomatoid 6%.≥ 2 metastatic sites: 84%. 10 pts were refractory to cytokine treatment and all progressed or experienced unacceptable toxicity after anti-angiogenic VEGFR-TKI treatment, Sunitinib (13 pts) or Pazopanib (5 pts). Median number of cycles was 7.5 (1–16). Overall, 72% of pts had disease control without significant correlations between response to prior therapy and hypertension. 14 pts had progression free survival (PFS) of 4.3 months (mos). 4 pts are still in treatment with a median PFS > 8 mos. Of 6 pts in which the dose was escalated, 3 benefitted with a PFS of > 3 mos. The most common toxicity (NCIC 3.0, all pts) was grade (g) ≥ 1 diarrhea in 10 pts, g2–3 hand-foot syndrome in 7 pts and g-3 mucositis in 1 pt. Other hematological and non-hematological toxicities were g1 with a frequency < 15%. Conclusions: Sorafenib at doses of 400–600 mg/BID/continuosly results in acceptable and well tolerated salvage treatment after VEGFR-TKI failure. In progressive patients, treatment with a higher dose could be a valid option. Final and mature data will be presented in combination with translational research evaluating biological characteristics on tissue and blood. No significant financial relationships to disclose.

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