Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Anthony P. Lam ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

299 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been achieved in trials evaluating drugs as single agents or in combination regimens. Paclitaxel has activity when used alone and in combination in urothelial cancer, and pazopanib is active in solid tumors secondary to its potent anti-angiogenic effect. We report the results of an ongoing multicenter phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Patients (pts) eligible for the study have histologically confirmed UC, with relapse after receiving up to 2 chemotherapeutic regimens. Pazopanib (800 mg) is administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment is continued until disease progression or unacceptable toxicity. Primary endpoint of the study is the response-rate (RR) based on RECIST criteria. Secondary endpoints include safety, and progression free-survival (PFS). For designing the study, Simon’s two-stage method was applied, and 9 pts were recruited in the first stage. After having ≥1 response in the first group, a full enrollment of 32 pts has been initiated. Results: 25 pts were enrolled from April 2010 to September 2013. Their median age was 67 years (47-89), with a median ECOG performance status of 1 (0-2). 10 pts (40%) had UC of the upper urinary tract and 15 had primary bladder/ureter tumors. All pts had multiple metastatic sites, including 11 (44%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Based on RECIST (v1.1) criteria,13 pts (52%) had partial response (PR), 5 (20%) had stable disease (SD), and 2 (8%) had complete response (CR) (80% clinical benefit). The side effects included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). 14 pts required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity of combining paclitaxel in relapsed/refractory UC. This combination is safe, and is worthy of evaluation in larger studies. Clinical trial information: 1108055.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.

1998 ◽  
Vol 16 (10) ◽  
pp. 3392-3397 ◽  
Author(s):  
L Sengeløv ◽  
C Kamby ◽  
B Lund ◽  
S A Engelholm
Keyword(s):  
Peripheral Neuropathy ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Complete Response ◽  
World Health ◽  
Eligibility Criteria ◽  
Metastatic Urothelial Cancer

PURPOSE Docetaxel and cisplatin has documented single-agent activity and different toxicity profiles in patients with metastatic urothelial cancer. We performed a phase II study in which docetaxel was combined with cisplatin to evaluate response rate, toxicity, and survival. PATIENTS AND METHODS Eligibility criteria included performance status (World Health Organization [WHO]) less than 3; normal bone marrow, liver, and renal function; and no concurrent malignancy or symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week. Patients received premedication with prednisolone and clemastine. RESULTS A total of 25 patients were assessable for response and toxicity. Median age was 64 years; five patients had locoregional disease only and 20 had metastatic disease. Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to 79%), including seven patients (26%) who achieved a complete response. Overall median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was observed in 56% of patients, but only one had febrile neutropenia. Mucositis and diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%, respectively. Fluid retention and hypersensitivity reactions were infrequent and mild. CONCLUSION The combination of docetaxel and cisplatin is effective and feasible in patients with metastatic urothelial cancer with a manageable safety profile.

Phase II Trial of Cisplatin, Gemcitabine, and Bevacizumab As First-Line Therapy for Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU 04-75

2011 ◽  
Vol 29 (12) ◽  
pp. 1525-1530 ◽  
Author(s):  
Noah M. Hahn ◽  
Walter M. Stadler ◽  
Robin T. Zon ◽  
David Waterhouse ◽  
Joel Picus ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
First Line ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

PurposeNovel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC.Patients and MethodsChemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2on day 1, gemcitabine 1,000 to 1,250 mg/m2on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days.ResultsForty-three patients with performance status of 0 (n = 26) or 1 (n = 17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progression-free survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met.ConclusionCGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study

1999 ◽  
Vol 17 (1) ◽  
pp. 25-25 ◽  
Author(s):  
M. J. Byrne ◽  
J. A. Davidson ◽  
A. W. Musk ◽  
J. Dewar ◽  
G. van Hazel ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Symptom Improvement ◽  
Median Response ◽  
Grade 3

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

Phase II study with preoperative oxaliplatin (O), cisplatin (P), 5-fluorouracil (F) (OPF) and radiation (XRT) in patients with esophageal (ES), gastroesophageal (GE), and gastric (G) cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15612-e15612
Author(s):  
M. Pera ◽  
R. Gallego ◽  
M. Martin-Richard ◽  
C. Montagut ◽  
M. Iglesias ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Performance Status ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Surgical Oncology ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria

e15612 Background: A phase I study showed the feasibility of the triplet combination (OPF) with XRT in ES and GE cancer (Maurel et al, IJRBOP, 2005). We conducted a phase II study to evaluate the efficacy of the regimen. Methods: Enrolled pts had resectable, high-risk (HR) based on endoscopic ultrasonography (EUS) (uT3, uN1 or uT4 if deemed resectable) ES, GE and G cancer. The primary objective was to determine the pathologic complete response (pCR). If 2 or more pCR were reported in the first 18 pts treated, enrollment continues with 23 additional pts. Eligibility criteria: squamous cell or adenocarcinoma of the ES, GE or G cancer and ECOG Performance status (PS) 0–1. Staging was done with EUS and computed spiral tomography. Laparoscopic staging was mandatory for pts with ES, GE and G adenocarcinoma. Pts received 2 cycles of O 85 mg/m2, P 55 mg/m2, F (3 g/m2 in 96h CI) q4w, with concomitant 45 Gy XRT in 25 fractions; surgery was planned 5–8 weeks after XRT. All pathological specimens were reviewed by a unique pathologist and regression analysis was recorded using Cologne (C) and M.D.Anderson (MDA) classification for ES and European Journal of Surgical Oncology (EJSO) for GE and G. Results: Between 5/04 to 12/07, 41 pts were enrolled in 5 Spanish Institutions. Median age 62 yrs (39–75 yrs); Male/female 83%/17%; PS 0/1 27%/73%; ES/GE/G 39%/32%/29%; EUS stageT3N0 (20%), T2–3N1 (65%) and T4 (10%). G3/4 adverse events included asthenia (27%), infection (7%), diarrhea (7%) and stomatitis (5%). There were 2 toxic deaths. Of the 31 pts who underwent surgery, there were R0=94%/R1=3%/R2= 3%. 7/41 pts (17%) achieved pCR. Using C and MDA classification, 9/14 (61%) and 12/14 (85%) ES achieved grade IV/III and P0/P1 regression, respectively. With EJSO classification 3/17 (18%) GE and G tumors achieved pCR. Median time to progression or death (PFS) was 16.2 (CI:12.2-NR) months (mo). Median overall survival (OS) was 28.9 mo. (CI: 22.5-NR). Conclusions: Although in the whole group pCR, PFS and OS does not appear superior to results achieved in other trials with preoperative P/F/XRT in HR pts, the OPF regimen seems specially active in ES cancer. No significant financial relationships to disclose.

Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
J. R. Fischer ◽  
F. Griesinger ◽  
T. Fink ◽  
E. Buchholz ◽  
T. Salm ◽  
...  
Keyword(s):  
Phase Ii ◽  
Partial Remission ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Benefit Risk Assessment

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Ultrafractionated radiation therapy (3x per day) for glioblastoma: Preliminary results of a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1570-1570
Author(s):  
P. D. Beauchesne ◽  
L. Taillandier ◽  
V. Bernier ◽  
M. Djabri ◽  
X. Michel ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase Ii ◽  
High Efficiency ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Who Grade ◽  
Primary Endpoints ◽  
Grade 3

1570 Background: Ultrafractionation radiation therapy consists in irradiating cells or tumors several times daily, delivering low doses at which hyperradiosensitivity occur. We recently reported the high efficiency of ultrafractionation radiotherapy in glioma cell lines and xenografts, and are now conducting a phase II clinical trial to determine the effect of an ultrafractionation regimen for glioblastoma patients. Methods: A prospective, multicenter, phase II study has opened for accrual in September 2003. Patients over 18 years of age who are able to give informed consent and have histologically proven, newly diagnosed and unresectable, supratentorial glioblastoma (WHO grade IV) are eligible. Three doses of 0.75 Gy spaced by at least four hours are delivered daily, five days a week for six consecutive weeks for a total of 67.5 Gy. Conformal irradiation includes the tumor bulk including a margin of 2.5 cm. Tolerance and toxicity are the primary endpoints; survival and progression-free survival are secondary endpoints. Results: To date 25 patients have been enrolled in this study, 19 currently evalualbe: 11 men and 8 women, median age 58 (range 37 to 76), median Karnofsky performance status (80 range from 70 to 100). The median time between histological diagnosis and the start of treatment is 7 weeks. The ultrafractionated radiation therapy has been well tolerated; no acute grade 3 and/or 4 CNS toxicity has been observed. Minor responses at the end of irradiation were seen in 5 patients. Median survival from initial diagnosis was 13.5 months, nine patients remain alive. Conclusions: Ultrafractionated radiation therapy is safe and well tolerated. No acute CNS toxicitiy has been observed. Overall survival of over 13 months for patients without prior debulking surgery compares favorably with other reports. Updated definitive results will be presented. No significant financial relationships to disclose.

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