Veliparib (Vel) in combination with chemoradiotherapy (CRT) of carboplatin/paclitaxel (C/P) plus radiation in patients (pts) with stage III non-small cell lung cancer (NSCLC) (M14-360/AFT-07).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8510-8510
Author(s):  
David E. Kozono ◽  
Tom Stinchcombe ◽  
Joseph Kamel Salama ◽  
Jeffrey Bogart ◽  
William J. Petty ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase 1 ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Phase 2 ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

8510 Background: CRT is standard treatment (Tx) for pts with unresectable stage III NSCLC. Vel, a potent oral PARP1/2 inhibitor, interferes with repair of chemotherapy- or radiation-induced DNA damage. In a phase 2 study, Vel showed favorable efficacy vs placebo when added to C/P in stage IV NSCLC. The reported phase 1 trial assessed the safety and efficacy of Vel + C/P-based CRT in Tx of stage III NSCLC (NCT02412371). Methods: Eligible pts (≥18 yr, unresectable stage III NSCLC, no prior NSCLC therapy) received Vel + CRT of weekly C area under the curve (AUC) 2 + P 45 mg/m2 weekly + 60 Gy (2 Gy/day) RT over 6–9 weeks (wk). Vel was dose escalated from 60 mg twice daily (BID) to 240 mg BID followed by Vel 120 mg BID added to consolidation therapy (CON) once every 3 wk of C AUC 6 + P 200 mg/m2 for 2 cycles (cohort 1–5). Cohort 6 received Vel 240 mg BID + CRT followed by Vel 240 mg BID + CON. Samples for pharmacokinetic (PK) analysis were collected on wk 4 day –3. The primary endpoint was to establish the recommended phase 2 dose (RP2D) of Vel + CRT/Vel + CON. Results: As of Sep 2018, 48 pts enrolled into cohorts 1–6 at Vel 60 mg/120 mg (n = 7), 80 mg/120 mg (n = 9), 120 mg/120 mg (n = 7), 200 mg/120 mg (n = 8), 240 mg/120 mg (n = 12), and 240 mg/240 mg (n = 5) added to CRT/CON; median age 65 yr (range, 48–81). Vel PK was dose proportional; 39 (81.3%) pts completed therapy. Grade ≥3 Tx-emergent adverse events (AEs) were reported in 37 (77.1%) pts; anemia and febrile neutropenia (10.4% each) were the most common. Serious AEs were observed in 19 (39.6%) pts. Dose-limiting toxicities occurred at 200 mg/120 mg (n = 1; influenza and pneumonia), 240 mg/120 mg (n = 1; insomnia), and 240 mg/240 mg (n = 2; febrile neutropenia, neutropenia, thrombocytopenia, esophagitis, suprapubic pain, sepsis); Vel 240 mg BID + CRT/Vel 120 mg + CON was chosen as the maximum tolerated dose/RP2D. Of 41 pts evaluable for tumor assessment, 26 (63.4%) had a confirmed response. Interim median progression-free survival was 24.1 mo (range, 8.9 – not reached); updated results will be reported. Conclusions: Vel 240 + CRT/Vel 120 mg BID + CON was well tolerated with promising antitumor activity in stage III NSCLC and was determined as RP2D. Clinical trial information: NCT02412371.

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8511-8511
Author(s):  
David R. Spigel ◽  
Corinne Faivre-Finn ◽  
Jhanelle Elaine Gray ◽  
David Vicente ◽  
David Planchard ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Stage Iii ◽  
Smoking History ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
The Pacific ◽  
Patient Reported ◽  
Stage Iii Nsclc

8511 Background: In the placebo-controlled Phase III PACIFIC trial of patients with unresectable Stage III NSCLC whose disease had not progressed after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab improved overall survival (OS) (stratified hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53–0.87; p=0.0025; data cutoff [DCO] Mar 22, 2018) and progression-free survival (PFS) (stratified HR 0.52, 95% CI 0.42–0.65; p<0.0001; DCO Feb 13, 2017) based on the DCOs used for the primary analyses, and the degree of benefit remained consistent in subsequent updates. Durvalumab was associated with a manageable safety profile, and did not detrimentally affect patient-reported outcomes, compared with placebo. These findings established consolidation durvalumab after CRT (the ‘PACIFIC regimen’) as the standard of care in this setting. We report updated, exploratory analyses of OS and PFS, assessed approximately 5 years after the last patient was randomized. Methods: Patients with WHO PS 0/1 (and any tumor PD-L1 status) whose disease did not progress after cCRT (≥2 overlapping cycles) were randomized (2:1) 1–42 days following cCRT (total prescription radiotherapy dose typically 60–66 Gy in 30–33 fractions) to receive 12 months’ durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (<65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). The primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the intent-to-treat (ITT) population. HRs and 95% CIs were estimated using stratified log-rank tests in the ITT population. Medians and OS/PFS rates at 60 months were estimated with the Kaplan–Meier method. Results: Overall, 709/713 randomized patients received treatment in either the durvalumab (n/N=473/476) or placebo (n/N=236/237) arms. The last patient had completed study treatment in May 2017. As of Jan 11, 2021 (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated treatment effect estimates for patient subgroups will be presented. Conclusions: These updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS plus durable PFS benefit with the PACIFIC regimen. An estimated 42.9% of patients randomized to durvalumab remain alive at 5 years and approximately a third remain both alive and free of disease progression. Clinical trial information: NCT02125461.

Weekly Carfilzomib, Cyclophosphamide and Dexamethasone (wCCyd) in Elderly Newly Diagnosed Multiple Myeloma Patients: Results of a Phase 2 Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1828-1828 ◽  
Author(s):  
Sara Bringhen ◽  
Davide Rossi ◽  
Alessandra Larocca ◽  
Paolo Corradini ◽  
Piero Galieni ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Board Of Directors ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Background Carfilzomib is a novel second generation proteasome-inhibitor with significant anti-MM activity and favorable toxicity profile. In a recent phase 1/2 study in relapsed/refractory patients (pts) a weekly schedule of carfilzomib in combination with dexamethasone showed to be effective (overall response rate of 77%) and safe (ASCO 2015). The ongoing phase 3 ARROW study is comparing once- with twice-weekly carfilzomib. In the newly diagnosed setting, no data are available on weekly carfilzomib. We designed a phase 1/2 study of weekly carfilzomib in combination with cyclophosphamide and dexamethasone (wCCyd) for newly diagnosed MM pts. Results of the dose-escalation phase 1 portion of study were previously reported (Palumbo A et al, Blood 2014), the maximum tolerated dose of weekly carfilzomib was established as 70 mg/m2. Here we report efficacy and safety results of the phase 2 portion of the study. Methods Newly diagnosed pts ineligible for autologous stem-cell transplantation due to age or co-morbidities were enrolled in the phase 2 portion of the study. Pts received IV carfilzomib at the maximum tolerated dose 70 mg/m2 on days 1, 8, 15 combined with oral cyclophosphamide at 300 mg/m2 on days 1, 8, 15 and oral dexamethasone at 40 mg on days 1, 8, 15, 22, in 28-daycycles. After the completionof 9 cycles, pts received 28-day maintenance cycles with carfilzomib at 70 mg/m2 on days 1, 8, 15 until disease progression or intolerance. The primary objectives were to determine the efficacy and safety of wCCyd. The secondary objectives included the evaluation of time to progression, progression-free survival, time to next therapy and overall survival. Response was assessed according to the modified International Uniform Response Criteria. Adverse events (AEs) were graded following NCI-CTCAE v4. Results As of July 15, 2015, 47 newly diagnosed MM pts were enrolled in the phase 2 portion of the study. Median age was 72 years, 23% of pts were older than 75 years, 30% had ISS stage III, 34% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. Toxicityand response data were available in 40 pts, who completed atleast the first cycle; 7 pts were still receiving their first cycle of treatment. Pts received a median of 6 cycles (range 1-9). Overall, 80% of pts achieved at least a partial response, 60% at least a very good partial response, and 28% a near complete response. Responses improved over time (Table 1). During the study, 9 pts progressed or died, the progression-free survival at 1 year was 75%. Grade (G) 3-4 drug-related adverse events included neutropenia (22%, 9 pts), thrombocytopenia (7%, 3 pts), infection (10%, 4 pts), acute pulmonary edema (5%, 2 pts), creatinine increase (5%, 2 pts), fever (2.5%, 1 pt), fatigue (2.5%, 1 pt) and headache (2.5%, 1 pt). G1-2 hypertension was reported in 6 pts (15%). No peripheral neuropathy was reported. Overall, the wCCyd regimen was well tolerated, 4 pts (10%) required carfilzomib dose-reduction (G3 hematologic toxicities [2 pts], G3 headache [1 pt] and G2 fatigue [1 pt]) and 9 pts (22%) required treatment discontinuation due to adverse events (2 infections, 1 acute pulmonary edema, 1 creatinine increase, 1 fever, 1 pt condition, 1 second tumor, 1 pericardial effusion, 1 sudden death). Conclusions This is the first prospective study evaluating once-weekly carfilzomib in treatment-naïve MM. wCCyd therapy appears safe and effective in newly diagnosed MM pts. Responses became deeper with subsequent cycles and toxicities were manageable. The response rate observed with weekly carfilzomib compares favorably with similar studies with standard twice-weekly carfilzomib infusion. Updated results will be presented at the meeting. Table 1. 2nd cycle 6th cycle 9th cycle Complete Response 17% 26% 33% At least near Complete Response 29% 39% 40% At least Very Good Partial Response 66% 82% 87% At least Partial Response 86% 87% 87% Disclosures Bringhen: Janssen-Cilag, Celgene, Novartis: Honoraria; Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Larocca:Janssen-Cilag, Celgene: Honoraria. Offidani:Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria. Gaidano:Celgene, Onyx: Membership on an entity's Board of Directors or advisory committees. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:Janssen-Cilag, Celgene, Onyx, Karyopharm: Honoraria, Research Funding; novartis: Honoraria. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria.

Dose intensive chemotherapy (Cx) in advanced thymoma: Initial report of Japan Clinical Oncology Group trials (JCOG 9605 and 9606)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7080-7080
Author(s):  
H. Kunitoh ◽  
T. Tamura ◽  
H. Fukuda ◽  
K. Nakagawa ◽  
K. Takeda ◽  
...  
Keyword(s):  
Thymic Carcinoma ◽  
Local Therapy ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Initial Report ◽  
Free Survival ◽  
Unresectable Stage ◽  
Short Course ◽  
Ecog Ps

7080 Background: Thymoma is considered to be sensitive to Cx. Dose intensive Cx might well be suitable for such tumors, especially in combination with local therapy. Objectives of the trials were to evaluate the safety and efficacy of the dose intensive CODE (cisplatin[C]- vincristine[O]- doxorubicin[D]- etoposide[E]) Cx in thymoma. The primary endpoint was progression-free survival time (PFS). Methods: Patients (pts) with 15–70 years of age with histologically documented Cx-naïve thymoma with stage IVa/IVb disease (JCOG 9605) or unresectable stage III disease (JCOG 9606) were eligible. Tumors of other histology, such as thymic carcinoma, carcinoid or lymphoma were excluded; pts were to have ample organ function and ECOG PS of 0–2. Myasthenia was allowed. Signed consent form was obtained. Pts received CODE Cx of 9 weeks (w): C 25 mg/m2 Cx day 1 on each w1–9; O 1mg/m2 d1 on w1,2,4,6,8; D 40 mg/m2 d1 and E 80 mg/m2 d1,2,3 on w 1,3,5,7,9. Cx courses were supported by GCSF. Steroids were used only for antiemesis. Those with stage III disease (JCOG 9606) went on to surgery, if judged to be resectable, and post-operative radiotherapy (RT) of 48Gy; those with unresectable disease received 60Gy RT. Results: From Jul./97 to Apr./05, 53 pts were entered to the studies. Five were found ineligible because of different histology. Pt characteristics and response to the Cx were summarized in the table . Toxicity of the Cx was mainly hematologic and generally well tolerated, with no toxic death; 70% of the pts completed planned 9 weeks. Thirteen pts in JCOG 9606 (stage III) received thoracotomy; tumor was resected in 11 pts, completely in 9 (39% of enrolled pts). Pathologic CR was observed in 3. The median PFS was 9.5m for stage IV and 4.5 y for stage III diseases. Overall survival at 2 & 5 yrs were 82% & 57% for stage IV and 96% & 77% for stage III pts. Conclusions: Short-course, dose intensive Cx was active against thymoma. Although it does not seem to bring long PFS in stage IV pts, it could improve resectability in limited disease. [Table: see text] No significant financial relationships to disclose.

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 1/2 study of safety/efficacy using trabectedin, ipilimumab, and nivolumab as first-line treatment of advanced soft tissue sarcoma (STS).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS46-TPS46 ◽  
Author(s):  
Erlinda Maria Gordon ◽  
Victoria S. Chua-Alcala ◽  
Katherine Kim ◽  
William W. Tseng ◽  
Doris M Quon ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Categorical Variables ◽  
Phase 2 ◽  
First Line ◽  
First Line Therapy ◽  
Number Of Patients

TPS46 Background: Sarcoma cells are most immunogenic at the onset of cancer when the immune system can recognize and destroy them. Hence, immune checkpoint inhibitors would be most effective when given as first line therapy. Objectives: (1) To investigate the maximum tolerated dose of trabectedin, an alkylating agent, when given sequentially with ipilimumab, a CTLA4 inhibitor, and nivolumab, a PD-1 inhibitor, in advanced STS, (2) To investigate the objective response rate (ORR), progression free survival (PFS) and overall survival (OS) , and (3) To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty patients ≥18 years of age with advanced STS will be enrolled. This is a phase 1/2 study using a defined dose of ipilimumab (1 mg/kg i.v. q 12 weeks), nivolumab (3 mg/kg i.v. q 2 weeks), and escalating doses of trabectedin (1.0, 1.3, 1.5 mg/m2 i.v. q 3 weeks). I. Dose Escalation Phase 1 (previously treated patients): The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 2 (previously untreated patients): An additional 22-28 patients will receive trabectedin at the MTD and defined doses of ipilimumab and nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: NIH CTCAE v4.03 and RECIST v1.1 will be used. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. The analyses of all study objectives will be descriptive and hypothesis generating, for planning Phase 2/3 studies. Clinical trial information: NCT 03138161.

scholarly journals Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9033-9033
Author(s):  
Josiah An ◽  
Melissa Yan ◽  
Nanmeng Yu ◽  
Adithya Chennamadhavuni ◽  
Muhammad Furqan ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Poor Response ◽  
Median Number ◽  
Stage Iii ◽  
University Of Iowa ◽  
Patient Demographics ◽  
Check Point Inhibitors ◽  
Stage Iii Nsclc ◽  
The University

9033 Background: STK11 mutation ( STK11m) in patients with stage IV NSCLC is associated with inferior survival and poor response to immune check point inhibitors (ICI). The significance of STK11m in patients (pts) with stage III NSCLC treated with concurrent chemoradiation (CCRT) with and without consolidation ICI is unknown. Methods: Patient demographics, disease characteristics, treatment received and outcomes in pts with stage III NSCLC that harbor STK11m were retrospectively reviewed from 4 cancer centers. A cohort of pts with stage III NSCLC and wild type STK11 (STK11w) from the University of Iowa served as a comparison group. SPSS version 25 was used for data analysis. Results: 75 pts with stage III NSCLC who had gene sequencing were included. 16/75 (21%) had STK11m. The clinical characteristics for the 16 STK11m and 59 STK11w pts showed ( STK11m vs. STK11w): mean age: 58 vs. 64 yrs, non-squamous histology: 11/16 (69%) vs. 37/59 (63%), KRAS co-mutation: 6/16 (38%) vs. 11/59 (19%), TP53 co-mutation: 9/16 (56%) vs. 15/59 (25%), PD-L1 ≥ 50%: 2/16 (13%) vs. 10/59 (17%), received CCRT 11/16 (69%) vs. 59/59 (100%) and consolidation ICI 6/16 (38%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 7 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). Progression free survival (PFS) for the STK11m vs. STK11w pts who received CCRT but not ICI was (4.2 vs. 34.3 months, respectively. P = 0.168), for the STK11m vs. STK11w pts who received CCRT and ICI was (11.3 vs. 17.5 months, respectively. P = 0.174), and for the STK11m vs. STK11w pts who received CCRT regardless of receiving ICI (11.3 vs. 32.9 months, respectively. P = 0.021). The median overall survival for STK11m pts (16 pts) was 25.5 months (95% CI, 13.7 to 37.2) while not yet reached for the STK11w group. Conclusions: In stage III NSCLC, STK11m was associated with inferior clinical outcomes. Larger studies are needed to identify the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.

scholarly journals Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique

2021 ◽  
Author(s):  
Carol Mansfield ◽  
Kelley Myers ◽  
Kathleen Klein ◽  
Jeetvan Patel ◽  
Antonio Nakasato ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Risk Tolerance ◽  
Stage Iii ◽  
Acceptable Risk ◽  
Treatment Benefit ◽  
Free Survival ◽  
Unresectable Stage ◽  
Melanoma Patients

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8538-8538 ◽  
Author(s):  
R. Gonzalez ◽  
K. Lewis ◽  
W. Samlowski ◽  
L. Cranmer ◽  
J. Catlett ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Melanoma Tumor ◽  
Minor Response ◽  
Unresectable Stage

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI50) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m2/day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ongoing. Results are available for the first 26 pts. Median age was 59 y/o, (range 29 - 88) with ECOG PS of 0–1. There is one objective response of intrabdominal lymph nodes based on Investigator assessment at Cycle 2 confirmed at Cycle 4; another patient had a minor response (24% reduction) at Cycle 6 (currently at Cycle 8). Two subjects have shown stable disease after 6 cycles and remain on study. The median number of cycles is 3 (range 1 - 9). Two of 26 pts reported a grade 3 AE considered possibly related to YM155 (chest pain - nos and catheter related thrombosis). Nineteen of 26 pts have discontinued the study (18 PD, 1 withdrew consent). Conclusions: YM155 induced responses in 2 pts and was generally well tolerated. Given this encouraging response as a single agent, studies of YM155 combined with other agents are under consideration. [Table: see text]

Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7188-7188
Author(s):  
J. R. Gray ◽  
D. R. Spigel ◽  
J. D. Hainsworth ◽  
E. Vazquez ◽  
J. D. Peyton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Large Cell ◽  
Research Network ◽  
Stage Iii ◽  
Stage Iiia ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Ecog Ps

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]

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