Efficacy and safety of dose-dense modified TCF regimen (TCF-dd) in metastatic or locally advanced gastroesophageal cancer (GEC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4112-4112
Author(s):  
Laura Toppo ◽  
Gianluca Tomasello ◽  
Wanda Liguigli ◽  
Margherita Ratti ◽  
Rossana Poli ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Intention To Treat ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Dose Dense ◽  
Metastatic Sites ◽  
Chemotherapy Efficacy

4112 Background: TCF is a standard first line option for GEC. The Norton-Simon hypothesis suggests that chemotherapy efficacy can be enhanced by decreasing intervals between cycles. We previously reported on the high activity of TCF-dd in GEC (Tomasello 2010). The aim of this study is to investigate the efficacy and safety of this intensified dose-dense regimen in a single-center large cohort of patients (pts). Methods: 150 pts with measurable or evaluable GEC, PS 0-2, with adequate organ function, treated in our center from 2004 to 2012 received TCF-dd: Docetaxel (60-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h continuous infusion d 1-2), plus Pegfilgrastim 6 mg d 3, every 14 days. Pts aged ≥ 65 years received the same schedule with a dose reduction by 30%. Analysis was based on the intention to treat population. Results: At a median follow-up of 44 months, 128 pts were evaluable for response, all for survival. Median age 65 (range 31-81), M:F 112:38. 17 pts (11%) with locally advanced inoperable GEC, 133 pts (89%) with metastatic GEC. Metastatic sites: liver 40%, peritoneum 31%, bone 14%, lung 12%. A median of 4 cycles (range 1-7) per patient was administered. 33% required a dose reduction. 33% were treated without any delay. 10 CR, 74 PR, 24 SD and 20 PD were observed, for an ORR of 66% (95% CI 57-74). Median OS was 13 months (95% CI 9.7-14.2). Most frequent grade 3/4 toxicities: neutropenia (34%), asthenia (28%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (11%), febrile neutropenia (10%), anemia (9%), and stomatitis (4%). 11 pts (7%) [7 metastatic, 4 locally advanced] became operable after TCF-dd and underwent surgery. We identified 12 metastatic pts (8%) with overall survival > 3 years and 7 (5%) still maintaining a long lasting CR at the time of the current analysis. Conclusions: TCF-dd in GEC is very active and may be an option for conversion therapy. Toxicity can be relevant and requires a careful monitoring.

Rate of durable complete remission (CR) using two sequential, dose-dense regimens of cisplatin, gemcitabine, paclitaxel (CGP) followed by m-VAC in patients with metastatic urothelial cancer (mUC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15502-e15502
Author(s):  
Matteo Brighenti ◽  
Stefano Panni ◽  
Bruno Perrucci ◽  
Mariangela Maltese ◽  
Wanda Liguigli ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Supportive Therapy ◽  
Complete Response ◽  
Improve Response Rate ◽  
Metastatic Urothelial Cancer ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Dose Dense ◽  
Metastatic Sites

e15502 Background: mUC is a chemotherapy sensitive tumor. Currently, CGP and MVAC are the most active regimens in this setting. According to Norton and Simon hypothesis, the administration of two sequential non cross-resistant, dose-dense chemotherapy regimens may target different cancer cells, avoid drug resistance, improve response rate and CR. Methods: Patients with histological diagnosis of mUC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP dose-dense (Gemcitabine 1000 mg/m2 d 1, Paclitaxel 140 mg/m2 d 1, Cisplatin 70 mg/m2 d 2 plus PegFilgrastim 6 mg on day 3, every 2 weeks) followed by 4 cycles of M-VAC (Methotrexate 30 mg/m2 d 1,Vinblastine 3 mg/m2 d 2, Doxorubicin 30 mg/m2 d 2, Cisplatin 70 mg/m2 d 2 plus Pegfilgrastim 6 mg on day 3 every 2 weeks). All were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for two years and 6 months thereafter. Metastatic sites included retroperitoneal nodes, lung, liver and bone. Results: From January 2007, 35 consecutive pts followed in the same oncology institution were included. Male were 74%; median age 65 years; median PS ECOG was 1; Bajorin risk factors was 0 in 37%, 1 in 43%, 2 in 20%. All pts were hospitalized for three days and received chemotherapy with hydration and supportive therapy. After the first 4 cycles of CGP we observed 14.3% CR, 48.6% PR, 22.9% SD and 14.3% PD. After the 4 sequential cycles of M-VAC we observed a global 37.1% of CR, 25.7% of PR, 8.6% of SD and 28.6% of PD. Median TTP was 9.9 months ( 95 % CI, 7.53-14.83) and median OS was 24.27 months ( 95 % CI, 10.03-38.43). Main grade 3–4 toxicity included asthenia ( 27%), anemia (21%), neutropenia (12 %), febrile (9%), thrombocytopenia (9%) and peripheral neuropathy (6 %). After a median follow up of 33 months, 6 of 13 patients who obtained a complete response are free of disease. Conclusions: These data confirm that the sequential use of this two dose-dense regimens is very active and 17 % of patients maintained a CR status.

A phase II study of dose-dense neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5104-5104
Author(s):  
Rajkumar Bikramjit Singh ◽  
Lalit Kumar ◽  
Subhash Chandra ◽  
B. K Mohanti ◽  
Sushmita Pathy ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Weekly Paclitaxel ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Grade 3 ◽  
Dose Dense

5104 Background: We prospectively studied dose dense neoadjuvant chemotherapy (NACT) designed for an enhanced cell kill, better local control and eradication of micrometastases prior to standard concurrent chemoradiation (CRT) in locally advanced cervical cancer. Methods: Between June 2010 and December 2011, 21 patients (median age - 51 years, range 35 - 67) of cervical cancer with locally advanced disease received NACT using paclitaxel (60mg/m2) and carboplatin (AUC-2) weekly for 6 doses. Patients (pts) then received concurrent CRT (external and brachytherapy) with weekly cisplatin (40mg/m2 for 6 doses) at a mean interval of 15 days (range 7–20 days). The primary end-point was response rate i.e. complete response (CR) and partial response (PR) 12 weeks post CRT. Results: Baseline stages were: stage 2A - 19%, 3B - 71.4%, 4A - 9.5%. Squamous cell carcinoma and adenocarcinoma constituted 95.2% and 4.7% pts respectively. Following NACT, 66.6% pts responded (CR -9.5% %; PR – 57.1 %), 23.8% had stable disease (SD) and 4.7% had progressive disease (PD). A total of 18 pts completed NACT and CRT of which 17 were in CR and 1 in PR. One patient with stage 4A disease developed vesicovaginal fistula at end of NACT for which she underwent pelvic exenteration and was in pathological CR. After NACT, one patient developed choroid metastases and was taken off study protocol while another patient was lost to follow up. At a mean follow up 5.8 months (range 1 - 14), 90% pts were in CR, 5% in PR and 5% had PD. During NACT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 33.3%, 4.7% & 9.5% of pts, respectively and grade 3/4 non-hematological toxicities in 9.5% pts. Following CRT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 25%, 5% and 10% of pts, respectively while 20% pts had grade 3/4 non-hematological toxicities. G-CSF was used in 30% pts during NACT and 25% pts during CRT, respectively. Conclusions: NACT with weekly paclitaxel and carboplatin followed by radical CRT is feasible and is associated with a high response rate in locally advanced cervical cancer. This approach needs to be studied in a phase III trial.

Long-term efficacy and safety outcomes of the modified (simplified) combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) as front-line therapy for unresectable or metastatic urothelial cancer (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 284-284
Author(s):  
Andrea Necchi ◽  
Luigi Mariani ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Efficacy And Safety ◽  
Metastatic Urothelial Cancer ◽  
Dose Dense

284 Background: MVAC and cisplatin-gemcitabine (CG) are the established standard of care for untreated patients (pts) with locally advanced-metastatic UC. CG is the preferred choice in most cases due to the better toxicity profile. Modifying MVAC by reducing side-effects may have the potential to improve efficacy. Methods: Data relative to unresectable T/N+/M+ pts entering sequential single-institution trials were collected. Chronologically, these changes to classic MVAC were provided: deletion of day 22 and administration of 25 mg/m2CDDP d2-5 (modified MVAC [mMVAC]); deletion of day 22 only, and deletion of days 15 and 22 in a 3-week schedule (simplified [s]MVAC1 and 2). 4-6 cycles were provided. Multivariable analysis was undertaken for recognized clinical variables. ITT analysis was applied. Results: From 09/86 to 04/12, 157 pts were treated (25 mMVAC, 72 sMVAC1, 60 sMVAC2). 84% had a bladder primary, 70% had distant metastases, 53% and 36% had nodal and visceral mets, respectively. 43.9% had a Bajorin score 1-2. 65.8% attained a complete (19.1%) or partial response (46.7%), 24.3% a stable disease, with no difference among regimens. After a median follow up of 87 mos (IQR 37-161), median (95% CI) PFS was 10.2 mos (8.4-10.8) and median OS was 19.5 mos (16.3-24.1). 2yr (95% CI) PFS and 5yr OS were 30.9% (23.8-40.1) and 25.3% (18.8-34.1). Responses were mainly seen in nodal mets (OR: 2.48, 95%CI, 1.12-5.54). Presence of visceral (HR: 2.42, 95%CI, 1.37-4.30), nodal mets (HR: 1.70, 95%CI, 1.07-2.69) and mMVAC regimen (HR: 1.73, 95%CI, 1.02-2.92) were negative prognostic factors for OS. G3-4 toxicities were similar among regimens and were 36% neutropenia, 14% thrombocytopenia, 12% anemia, 10% mucositis, and 4% renal toxicity. 2 pts died for toxicity. Conclusions: Simplifying MVAC schedule may result in improved activity and efficacy while reducing toxicity. Though retrospective, the combined results of MVAC modification would claim a benefit over either classic/dose-dense MVAC or CG in terms of efficacy and safety. A reappraisal of the upfront management of advanced/metastatic UC is warranted.

Nab-paclitaxel/S-1(AS) versus nab-paclitaxel/gemcitabine(AG) for first-line chemotherapy in advanced pancreatic ductal adenocarcinoma (aPDAC): A retrospective analysis of efficacy and safety.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15743-e15743 ◽  
Author(s):  
Yuan Zong ◽  
Zhi Peng ◽  
Ming Lu ◽  
Xicheng Wang ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Primary Lesion ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Efficacy And Safety ◽  
Phase Ii Trials ◽  
First Line ◽  
Intention To Treat ◽  
Grade 3 ◽  
Line Chemotherapy

e15743 Background: AG significantly improved PFS and OS compared with gemcitabine monotherapy in patients (pts) with metastatic PDAC, but the confirmed ORR was limited to 23% with increased grade 3 or 4 myelosuppression. In GEST and JASPAC01 studies, S-1 showed non-inferior or superior activity to gemcitabine in advanced and postoperative PDAC. S-1 also developed less hematologic adverse events especially in neutropenia and was a convenient oral alternative. Two single-arm phase II trials in China demonstrated high ORR of 50.0-53.1% with AS. We investigated the efficacy and safety of first-line chemotherapy with AS versus AG in pts with aPDAC. Methods: A retrospective review was conducted of aPDAC pts treated with first-line AS and AG in GI dpt. Of PUCH between 11/2013 and 12/2018. Pts received 125mg/m2 nab-paclitaxel intravenously (IV) on day1, and 80-100mg S-1 orally per day on day1-7 every two weeks in AS cohort, while pts received 125mg/m2 nab-paclitaxel IV on day1,8, and 1000mg/m2 gemcitabine IV on day1,8 every three weeks in AG cohort. ORR, ORR of primary lesion, DCR, PFS, OS and safety were analysed between two cohorts. Survival outcomes were evaluated by Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazard model was made to determine independent predictors of survival. Results: A total of 70 pts (45 in AS cohort, 25 in AG cohort) with locally advanced (4%) and metastatic (96%) PDACs were identified. 75% were male and the median age was 65(range 36-72). Among intention-to-treat population, the ORR and DCR were 40.0% vs 32.0% (p = 0.70) and 75.6% vs 64.0% (p = 0.57) in AS and AG cohort, respectively. The ORR of primary lesion was 31.1% with AS vs 20.0% with AG (p = 0.73). With the median follow-up of 9.8 months(range 2.3-22.2), the median PFS and OS were 4.7m vs 6.7m (HR, 1.2; 95% CI, 0.6 to 2.4; p = 0.62) and 10.3m vs 11.3m (HR, 0.9; 95% CI, 0.5 to 1.8; p = 0.78) in AS and AG cohort, respectively. Grade 3/4 toxicities occurred in 31.1% AS vs 36.0% AG (p = 0.59). Most G3/4 toxicities were: leukopenia/neutropenia (26.7% vs 20.0%), febrile neutropenia (2.2% vs 8.0%), thrombocytopenia (0 vs 12%), fatigue (4.4% vs 12%), peripheral neuropathy (0 vs 8.0%). In multivariate analysis, liver metastasis was the only independent predictor of poor OS (HR 0.3, 95%CI 0.1-0.8, p = 0.014). Conclusions: AS was a comparable and convenient alternative with manageable toxicities in aPDAC. There was a trend towards improved ORR of primary lesion compared with AG.

The efficacy and safety of toripalimab combined with definitive chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16043-e16043
Author(s):  
Mian Xi ◽  
Yujia Zhu ◽  
Qiao-Qiao Li ◽  
Lei Zhao ◽  
Yadi Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Esophageal Squamous Cell Carcinoma ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Advanced Esophageal Cancer ◽  
Definitive Chemoradiotherapy ◽  
Genetic Biomarkers ◽  
Grade 3

e16043 Background: Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, the loco-regional and distant recurrences after definitive CRT were as high as 50%. Immunotherapy targeting the PD-1/PD-L1 axis has demonstrated antitumor activity in advanced esophageal cancer. With the potential benefit of combining PD-1 blockade to CRT, we performed a phase II trial to evaluate the efficacy and safety of the combination of toripalimab (an anti-PD-1 antibody) and definitive CRT in locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with previously untreated, unresectable, stage II–IVA ESCC were enrolled. Patients received concurrent radiotherapy (50.4 Gy in 28 fractions), chemotherapy (weekly paclitaxel 50 mg/m2 and cisplatin 25 mg/m2 for 5 cycles), and toripalimab (240 mg, every 3 weeks until 12 months or disease progression). The primary endpoint was clinical complete response (cCR) rate at 3 months after CRT according to PET-CT scan and esophagogastroduodenoscopy with biopsies. Second endpoints were overall survival (OS), progression-free survival (PFS), adverse events (AEs). Exploratory endpoints included PD-L1 expression, tumor mutational burden, and genetic biomarkers as potential efficacy predictors. Results: Between November 2019 and December 2020, 42 eligible patients (2 stage II, 19 stage III, and 21 stage IVA) were included. Of them, 39 completed CRT and 3 remained under treatment. Twenty-eight patients were included for efficacy analysis (median follow-up: 7.2 months) and 42 for safety analysis (median follow-up: 5.8 months). The cCR rate was 60.7% (17/28) and the median OS and PFS were not reached. Thirty-nine patients (92.9%) had AEs, 20 patients (47.6%) experienced grade ≥3 AEs, and 1 patient (2.4%) suffered grade 5 esophageal fistula. The most common grade ≥3 AEs were lymphopenia (45.2%), neutropenia (33.3%), and anemia (28.6%), respectively. Conclusions: The addition of toripalimab to definitive CRT for locally advanced ESCC demonstrated encouraging efficacy and acceptable toxicity. The exploratory endpoints including PD-L1 expression and genetic biomarkers analyses are ongoing. Clinical trial information: NCT04005170.

scholarly journals Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhei Miyasaka ◽  
Hidemasa Kawamura ◽  
Hiro Sato ◽  
Nobuteru Kubo ◽  
Tatsuji Mizukami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Therapeutic Benefit ◽  
Carbon Ion Radiotherapy ◽  
Safety And Efficacy ◽  
Carbon Ion ◽  
Grade 3 ◽  
Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

scholarly journals Role of interstitial brachytherpy using template (mupit) in locally advanced carcinoma cervix

2016 ◽  
Author(s):  
Ashish Bhange ◽  
Abhishek Gulia ◽  
Anirudh Punnakal ◽  
Anil Kumar Anand ◽  
Anil Kumar Bansal ◽  
...  
Keyword(s):  
Local Control ◽  
Residual Disease ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Interstitial Brachytherapy ◽  
Carcinoma Cervix ◽  
Advanced Carcinoma ◽  
Needle Position ◽  
Grade 3

Introduction: Locally advanced carcinoma cervix includes stages IIB, IIIA, IIIB and IVA. Interstitial brachytherapy has the potential to deliver adequate dose to lateral parametrium and to vagina. Hence, it is preferable in cases with distorted anatomy, extensive (lower) vaginal wall involvement, bulky residual disease post EBRT and parametrium involvement upto lateral pelvic wall. Aim and Objective: To determine clinical outcome and complications (acute and chronic) in locally advanced carcinoma cervix, treated with interstitial brachytherapy using template (MUPIT - Martinez universal perineal interstitial template). Materials and Methods: This study is a retrospective analysis of 37 cases of locally advanced carcinoma cervix (stage IIB-2, IIIB-30, IVA-5), treated with EBRT (dose-median 45Gy/25#) ± concurrent chemotherapy (CCT) - Inj. Cisplatin/Inj Carboplatin, followed by interstitial brachytherapy using MUPIT from December 2009 to June 2015. Initial treatment with EBRT ± CCT was followed by intertstitial brachytherapy. Under spinal anaesthesia and epidural analgesia, MUPIT application was done. Straight and divergent needles (median 26, range 19-29) were inserted to cover parametrium adequately. Needle position was verified with planning CT scan and Brachytherapy planning was done. Dose was normalized to 5 mm box surface from outermost needle with optimization of dose to OAR (Bladder, Rectum and Sigmoid colon). Prescription dose –25Gy in 5#. Treatment was delivered by Microselectron HDR using Ir192 source. Treatment fractions were delivered twice daily with min 6 Hrs. gap in-between fractions. Results: The median duration of follow-up was 25 months. Local control was achieved in 28 patients with residual disease in 7 patients and local recurrence in 2 patients. 10 patients had acute lower GI toxicity {Grade1 (n=6), Grade 2 (n=4)}, 2 patients had acute Grade 1 bladder toxicity. 1 patient had grade 3 and 1 patient had grade 4 chronic bladder toxicity. Chronic rectal toxicity was seen in 10 patients {Grade 2 (n=4), Grade 3 (n=4), Grade 4 (n=2)}. Conclusion: Local control was achieved in 28/37 patients (75.6%) and overall survival rate of 81.1% at median follow up of 25 months in patients with locally advanced carcinoma cervix and unfavorable prognostic factors.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

scholarly journals 354 Lenvatinib and pembrolizumab in advanced endometrial carcinoma (EC): long-term efficacy and safety update from a phase 1b/2 study

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A381-A381
Author(s):  
Vicky Makker ◽  
Carol Aghajanian ◽  
Allen Cohn ◽  
Margarita Romeo ◽  
Raquel Bratos ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Center ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Efficacy Analysis ◽  
Phase 1B ◽  
Grade 3 ◽  
Cutoff Date

BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. Pembrolizumab is an anti-programmed death-1 monoclonal antibody. We previously reported results from a cohort of 108 patients with metastatic EC (data cutoff date, January 10, 2019) who received lenvatinib + pembrolizumab as part of an ongoing multicenter, open-label, phase 1b/2 study evaluating the combination treatment in patients with selected solid tumors (NCT02501096). Lenvatinib + pembrolizumab showed a tolerable safety profile and promising antitumor activity per immune-related (ir) Response Evaluation Criteria In Solid Tumors (RECIST) by investigator assessment, including an objective response rate (ORR) of 38.9% (95% confidence interval [CI], 29.7–48.7), median progression-free survival (PFS) of 7.4 months (95% CI, 5.3–8.7), and median overall survival (OS) of 16.7 months (95% CI, 15.0-not estimable).1 Here we present updated efficacy and safety data (data cutoff date: August 18, 2020).MethodsPatients included in the EC cohort had histologically confirmed, measurable metastatic EC and had received ≤2 prior chemotherapies (unless discussed with the sponsor). Patients received lenvatinib (20 mg orally once daily) and pembrolizumab (200 mg intravenously once every 3 weeks). The phase 2 efficacy endpoints included ORR, PFS, OS, and duration of response. Tumor assessments for primary and secondary endpoints were evaluated by investigators per irRECIST.ResultsThe 108 patients from the key efficacy analysis set for the previously reported results were all included in these updated analyses. Median follow-up duration for the study was 34.7 months. Efficacy outcomes are summarized in table 1. Treatment-related adverse events (TRAEs) occurred in 104 (96%) patients (94 [87%] grade ≤3, 10 [9%] grade ≥4). TRAEs led to study-drug interruption of 1 or both drugs in 80 (74.1%) patients and dose reductions of lenvatinib in 73 (67.6%) patients; 23 (21.3%) patients discontinued 1 or both drugs due to a TRAE. The most common grade ≥3 TRAEs were hypertension (33.3%), lipase increased (9.3%), fatigue (8.3%), and diarrhea (7.4%).Abstract 354 Table 1ConclusionsWith extended follow-up, our updated efficacy analysis continued to show clinical benefit in patients with metastatic EC who received lenvatinib + pembrolizumab. Moreover, the combination had a manageable safety profile that was generally consistent with the established safety profiles of the individual monotherapies. No new safety signals were detected. A phase 3 study of lenvatinib + pembrolizumab versus treatment of physician’s choice in advanced endometrial cancer further supports the lasting clinical benefits observed in our study.2Trial Registration www.clinicaltrials.gov NCT02501096ReferencesMakker V, Taylor MH, Aghajanian C, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 2020;38(26):2981–2992.Makker V, Colombo N, Casado Herráez A, et al. A multicenter, open-label, randomized, phase 3 study to compare Ethics ApprovalThis study was approved by the following ethics committees/institutional review boards (IRBs): Oregon Health & Sciences University IRB, IntegReview IRB, Memorial Sloan Kettering Cancer Center IRB, University of Pennsylvania Office of Regulatory Affairs IRB, Dana-Farber Cancer Institute IRB, The University of Chicago Biological Sciences Division IRB, University of Texas MD Anderson Cancer Center IRB, Western IRB, Quorum Review IRB, US Oncology, Inc. IRB, CEIm - Comité de Ética de la Investigación con Medicamentos, Regional Komite for Medisinsk og Helsefagli Forskningsetikk, and REC - Regional Committees for Medical and Health Research Ethics. All participants gave informed consent before taking part in this study.ConsentNo identifying information is contained in this abstract so no permission from participants is considered necessary.

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