scholarly journals Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study

2020 ◽  
Vol 12 ◽  
pp. 175883592097084
Author(s):  
Keke Nie ◽  
Ling Zhang ◽  
Yunhong You ◽  
Hongmei Li ◽  
Xiuhui Guo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Pancreatic Adenocarcinoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Patient Death ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Secondary Endpoints ◽  
Study Population ◽  
Grade 3 ◽  
Moderate Nausea

Objective: To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma. Patients and methods: Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m2 and oxaliplatin 85 mg/m2 on day 1, and oral S-1 40 mg/m2 twice daily on days 1–14, repeating the regimen every 21 days until one of the following occurred: disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021. Results: A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI): 2.83–5.88] and the median OS was 11.00 months (95% CI: 9.16–12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively. The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed. Conclusion: Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Weekly docetaxel in patients with metastatic breast cancer: A Bangladeshi perspective.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11533-e11533
Author(s):  
Ehteshamul Hoque ◽  
Shanaz Karim ◽  
Rakib Uddin Ahmed
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Docetaxel ◽  
Previous Regimen ◽  
High Antitumor Activity ◽  
Grade 3

e11533 Background: Docetaxel has demonstrated high antitumor activity in first and second line treatment of metastatic breast cancer. Usually it is administrated three weekly at a dose of 75mg/ m2. We evaluated the efficacy and toxicity of Docetaxel in metastatic breast cancer in weekly bases. This study analyzed the efficacy and toxicity of docetaxel given weekly. Methods: Thirty eight patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks interval. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression or death. All patients had received prior chemotherapy. Of them 32 patients previously received anthracycline-containing regimens and 5 patients had received taxane based regimens. Results: Out of thirty eight patients thirty seven were evaluable. There was one complete response (3%), 11 patient has partial responses (30%), 17 patients with stable disease (46%) and six with disease progression (16%). Overall response rate was 78%. Median progression-free survival was 9.2 months. Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1–2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haemalotoxicity and stopped in one patient due to painful nail toxicity. Conclusions: Docetaxel is effective in three weekly regimens. In our study we found weekly docetaxel is as effective as the previous regimen. The efficacy of weekly docetaxel (35 mg/m2) can be an effective schedule for metastatic breast cancer who has received chemotherapy previously. The toxicity in this regimen is very low and manageable.

Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15176-e15176 ◽  
Author(s):  
Matheus Bongers Alessandretti ◽  
Erika Pereira Brandao ◽  
Carina Meira Abrahão ◽  
Aline Rocha Lino ◽  
Rodnei Macambira Junior ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Location ◽  
Ethical Committee Approval ◽  
Head Of The Pancreas ◽  
Grade 3 ◽  
Few Data ◽  
Advanced Pancreatic Adenocarcinoma

e15176 Background: Few data regard efficacy and safety of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, fluorouracil bolus of 400 mg/m2 and continuous infusion of 2400 mg/m2 over 46 hours and leucovorin 400 mg/m2) in patients over 65 years with advanced pancreatic adenocarcinoma. Methods: After Ethical Committee approval, consecutive patients age over 65 with biopsy proven pancreatic adenocarcinoma that received at least one cycle of modified dose-attenuated FOLFIRINOX (no bolus FU and reduced dose of at least one agent since first cycle) were selected (São José Hospital database) for a retrospective review for safety, response, and survival. Results: Nineteen consecutive patients were selected from our database. Patients characteristics included 12 (63,1%) males, 7 (36,9 %) females, median age 72,7 (range 66-79). Tumor location was 11 (57,8 %) head of the pancreas, 6 (31,57 %) body and 2 (11 %) in other sites. Grade 3/4 toxicities were reported in 10 patients (52,6 %): nausea/vomiting 1 (5,2 %), diarrhea 1 (5,2 %), fatigue 3 (15,7%), neutropenia 4 (21 %), thrombocytopenia 1 (5,2%) and febrile neutropenia 3 (15,6 %). Elevations in AST and ALT above the upper limit of normality were identified in 5 (26,31%). No deaths reported due to toxicity. Prophylactic granulocyte colony stimulator factor (G-CSF) was given to 14 (73 %). Seventeen patients completed at least four cycles; disease control was obtained in 15 (83, 3 %) with 1 complete response, 5 partial response and 9 stable diseases. Median reductions in doses in the first cycle of chemotherapy by drugs were: oxaliplatin 23,3 % (10%-30%), irinotecan 24,6 % (0%-60%), fluorouracil 20,6% (0%-40%). Median reductions in doses in the fourth cycle of chemotherapy by drugs were: oxaliplatin 20,8 % (0%-42%), irinotecan 24,9 % (0%-75%), fluorouracil 17,6% (0%-40%).With a median follow up of 4.5 months, median overall or progression free survival is not reached. Conclusions: Modified dose-attenuated FOLFIRINOX is a therapeutic option to elderly with advanced pancreatic adenocarcinoma. Although grade 3 and 4 toxicities were reported, they were manageable. Modified attenuated-dose of FOLFIRINOX needs further investigated.

Phase I/II study of ramucirumab plus nivolumab in patients in second-line treatment for advanced gastric adenocarcinoma (NivoRam study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 129-129 ◽  
Author(s):  
Hiroki Hara ◽  
Hirokazu Shoji ◽  
Daisuke Takahari ◽  
Taito Esaki ◽  
Nozomu Machida ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Second Line ◽  
Phase 2 ◽  
Primary Analysis ◽  
Secondary Endpoints ◽  
Advanced Gastric Adenocarcinoma ◽  
Grade 3 ◽  
Line Chemotherapy

129 Background: Nivolumab (Nivo) showed a survival benefit in salvage line of advanced gastric cancer (AGC) patients in ATTRACTION-2 trial. Based on synergistic anti-tumor effects by simultaneous blockade of PD-1 and VEGFR-2, this phase 1/2 study was conducted to investigate the safety and efficacy of Nivo plus ramucirumab (Ram) in the second line chemotherapy for AGC. Methods: AGC patients with measurable lesions, PS 0-1, disease progression on first line chemotherapy containing platinum were eligible. Patients received Nivo (3mg/kg, Q2W) and Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase 1 part), additional 40 patients were required in a phase 2 part with the primary analysis (expected 6-months progression-free survival (PFS) rate of 36%, threshold of 18%, one-sided alpha level of 10%, power of 90%). Secondary endpoints included overall response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. Results: 46 AGC patients (median age 66 years, PS 1 40%) were enrolled. No dose limiting toxicities were observed in the phase 1 part. With median follow up time of 10.2 month, 6-month PFS rate was 37.4% (90% confidential intervals: 25.7-49.2%), which met the primary endpoint of the phase 2 part. ORR/DCR were 26.7%/62.2%. Median PFS/OS were 2.9/9.0 months. Among all enrolled patients, grade 3 or 4 treatment related adverse events were hypertension (n = 2), diarrhea (n = 2), perforation at jejunum (n = 1), hemorrhage (n = 1), colitis (n = 1), pancreatitis (n = 1), liver dysfunction (n = 1), cholangitis (n = 1), hematoma (n = 1), neutropenia (n = 1) and proteinuria (n = 1). There were no treatment-related deaths. Conclusions: Combination of Nivo and Ram showed promising antitumor activity and mild toxicity profile for second line AGC, which is worth evaluating in a further confirmatory study. Clinical trial information: NCT02999295.

Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): Results of a multicenter phase II international thyroid oncology group trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6512-6512 ◽  
Author(s):  
Bryan Haugen ◽  
Jena French ◽  
Francis P. Worden ◽  
Bhavana Konda ◽  
Eric Jeffrey Sherman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Time ◽  
Phase Ii ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maculopapular Rash ◽  
Multicenter Phase ◽  
Secondary Endpoints ◽  
Grade 3

6512 Background: Lenvatinib is an approved therapy for patients with RAIR DTC. While the overall response rate (ORR) is high, few patients achieve a complete response (CR) and most patients eventually have progressive disease (PD). Combination lenvatinib and pembrolizumab is being explored in many different cancers, and this combination has been approved for advanced endometrial carcinoma. Methods: Patients with RAIR DTC with Response Evaluation Criteria in Solid Tumor (RECIST v1.1) measurable PD (<14 months (mo) prior to registration) were enrolled in this single-arm multicenter phase II study. Patients were excluded if they had received previous VEGFR-directed multikinase therapy. The lenvatinib starting dose was 20 mg/day orally and pembrolizumab was 200mg IV every 3 weeks. The primary endpoint was CR. ORR, progression-free survival (PFS) and safety graded by Common Terminology Criteria for Adverse Events v4.0 were secondary endpoints. Results: Thirty patients were enrolled. The median age was 62.5 years, and 53% of the patients were women. Seventy percent of patients had grade 3 adverse events (AEs) and 10 percent had grade 4 AEs. There were no treatment-related deaths. The most common > grade 3 AEs were hypertension (47%), weight loss (13%), maculopapular rash (13%), leukopenia (7%), diarrhea (7%) and oral mucositis (7%). Twenty-one patients (70%) required lenvatinib dose reduction. Of 29 evaluable patients, 18 (62%) had a partial response (PR) and 10 (35%) had stable disease (SD). The clinical benefit rate (ORR +SD) was 97%. Median time to tumor nadir was 7.4 mo (1.6-17.8 mo). Median PFS was not yet reached. The PFS at 12 months was 74%. Median time on therapy was 9.9 mo (3.2-18.9 mo). Fourteen patients are continuing therapy (7.6-18.9 mo). Six of these patients (43%) have not yet reached tumor size nadir. Three patients (10%) had > 80% target tumor shrinkage. Conclusions: Lenvatinib plus pembrolizumab is reasonably tolerated in patients with RAIR DTC. To date, there have been no documented complete responses. Combination lenvatinib plus pembrolizumab therapy has a high ORR in patients with RAIR DTC. Continuation of this study will help determine the depth and length of the responses. Clinical trial information: NCT02973997 .

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Aiwu Ruth He ◽  
Thomas Yau ◽  
Chiun Hsu ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Subgroup Analyses ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.

Paclitaxel, ifosfamide, and cisplatin (TIP) efficacy for first-line treatment of patients (pts) with intermediate- or poor-risk germ cell tumors (GCT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4501-4501
Author(s):  
Darren Richard Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Sujata Patil ◽  
Lindsay Joy Van Alstine ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Neutropenic Fever ◽  
First Line ◽  
Poor Risk ◽  
Study Results ◽  
Secondary Endpoints ◽  
Grade 3

4501 Background: Durable progression-free survival (PFS) rates for pts with intermediate- and poor-risk GCT approximate only 75% and 50%, respectively with standard BEP. This multicenter phase II study investigated first-line TIP in this population. Methods: Pts age ≥18 with untreated, IGCCCG intermediate- (LDH modified to ≥3x upper limit of normal) or poor-risk GCT were eligible. Pts received 4 cycles of TIP every 21 days, consisting of paclitaxel 120mg/m2 days 1-2; ifosfamide 1200mg/m2 days 1-5; and cisplatin 20mg/m2days 1-5, followed by G-CSF and levofloxacin for neutropenic fever prophylaxis. The primary endpoint was the complete response (CR) rate; secondary endpoints included PFS and toxicity. A Simon’s 2-stage design required a CR in ≥11/18 pts to proceed to stage 2, where with ≥27/41 CRs overall, the regimen would be considered active and worthy of further study. Results: Of 44 men (median age 27) enrolled; 38 had nonseminoma and 6 seminoma; 29 were poor-risk and 15 intermediate-risk. Primary site was testis in 30, mediastinum in 11, and retroperitoneum in 3. 42 pts had elevated markers and 14, 6, and 1 had liver, bone, and brain metastasis, respectively. The trial met its primary endpoint; of 41 evaluable pts, 28 achieved a CR (see Table) and 6 pts (5 with seminoma) achieved a partial response with negative markers (PR-). Two pts relapsed. With a median follow-up of 2.2 years, estimated 3-year PFS was 79% and 3-year overall survival (OS) 98% (see Table). There were no treatment-related deaths. Grade 3/4 toxicities were primarily hematologic and 6 (14%) pts developed neutropenic fever. Conclusions: TIP demonstrates promising efficacy and is well-tolerated in intermediate- and poor-risk GCT pts. A randomized trial of TIP vs. BEP has been initiated to compare efficacy. Clinical trial information: NCT00470366. [Table: see text]

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 91-91
Author(s):  
Geoffrey Y. Ku ◽  
Yelena Yuriy Janjigian ◽  
Manish A. Shah ◽  
Jessica Herrera ◽  
Laura H. Tang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Secondary Endpoints ◽  
Grade 3

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.

Phase II study of bevacizumab (Bv) in combination with paclitaxel-carboplatin (PC) as first-line chemotherapy for nonsquamous (SQ) non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19021-e19021
Author(s):  
Motohiro Tamiya ◽  
Tomonori Hirashima ◽  
Akihiro Tamiya ◽  
Norio Okamoto ◽  
Hidekazu Suzuki ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Complete Response ◽  
Severe Bleeding ◽  
Vascular Endothelial ◽  
Bleeding Events ◽  
Overall Response ◽  
Grade 3 ◽  
Endothelial Growth Factor

e19021 Background: Vascular endothelial growth factor (VEGF) plays an important role in NSCLC with MPE, but the evidence regarding the efficacy of Bv with PC for treatment of NSCLC with MPE is lacking. Therefore, we prospectively evaluated the efficacy and safety of Bv and PC in non-SQ NSCLC pts. Methods: Chemotherapy-naive non-SQ NSCLC pts with MPE were eligible to participate. Pleurodesis before chemotherapy was not allowed. The treated pts received PC without Bv in the first cycle to prevent Bv-induced delayed wound healing after chest drainage. Subsequently, they received 2–6 cycles of PC with Bv. Patients who completed more than 3 cycles of PC and Bv without disease progression or severe toxicities continued to receive Bv alone as a maintenance therapy. The primary endpoint was overall response, although an increase in MPE was allowed in the first cycle. The plasma and MPE VEGF levels were measured at baseline and the plasma VEGF levels after 3 cycles of chemotherapy. Results: Between September 1, 2010 and June 30, 2012, 23 pts were enrolled. The overall response rate was 60.8%, and the disease control rate was 87.0%. No pts showed complete response, 14 showed partial responses, 6 showed stable disease, 2 showed disease progression, and 1 died in the first cycle. Sixteen pts received maintenance therapy, following a median of 3 cycles. The median progression-free survival period for all pts was 200 days (95% CI, 156–263 days), whereas the median overall survival was 328 days (95% CI, 206–415 days). All pts experienced high levels of hematological toxicities, with most pts experiencing neutropathic toxicities above grade 3. However, none of the pts experienced severe bleeding events. The median baseline MPE VEGF level was 1798.6 (range, 223.4–35,633.4) pg/mL. The plasma VEGF levels showed a significant decrease after 3 chemotherapy cycles (baseline, 513.6 ± 326.4 pg/mL; post-chemotherapy: 25.1 ± 14.1 pg/mL; p < 0.01), regardless of the degree of efficacy. Conclusions: The combination of PC with Bv was confirmed to be effective and reasonably well-tolerated in chemotherapy-naïve non-SQ NSCLC pts with MPE. Clinical trial information: UMIN000005284.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
Thomas Yau ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
Anthony B. El-Khoueiry ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4012 Background: NIVO monotherapy (mono) is approved for sorafenib (SOR)-treated pts with HCC based on data from CheckMate 040 (NCT01658878), which reported an objective response rate (ORR) of 14% and median overall survival (mOS) of 16 months (mo). This is the first report of efficacy and safety of the NIVO + IPI combination in SOR-treated pts with aHCC. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety and tolerability. Secondary endpoints included ORR (BICR per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS. Cutoff was 25 Sep 2018. Results: 148 SOR-treated pts were randomized. Minimum follow-up for OS from last pt randomization date to data cutoff was 24 mo. At baseline: 88% had vascular invasion or extrahepatic spread, 91% had BCLC stage C, 84% discontinued SOR due to disease progression and 14% due to toxicity. Overall, ORR was 31% (7 had a complete response [CR]) with a median DOR of 17 mo; DCR was 49% and 24-mo OS rate was 40%. Pts in arm A had a mOS of 23 mo and 4 pts had a CR. The table shows additional efficacy results by arm. Overall, NIVO + IPI was well tolerated; 37% of pts had a grade 3–4 treatment-related adverse event (TRAE; most common: pruritus and rash); 5% had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + IPI led to clinically meaningful responses and had an acceptable safety profile in SOR-treated pts, with an ORR twice that of NIVO mono (31% and 14%, respectively). Pts in arm A had the most promising mOS of 23 mo. Clinical trial information: NCT01658878. [Table: see text]

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