A phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma

2020 ◽  
Author(s):  
Kageaki Watanabe ◽  
Yusuke Okuma ◽  
Shoko Kawai ◽  
Makoto Nagamata ◽  
Yukio Hosomi
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Pleural Mesothelioma ◽  
Previously Treated ◽  
Number Of Treatment

Abstract Background Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. We conducted a phase II trial of this drug in patients with previously treated MPM.Methods Eligible patients with MPM having adequate organ function and a performance status of 0–2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1–3 every 3 weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate (ORR). Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events (AEs) were evaluated as secondary endpoints.Results This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2–11.2) months, and the median OS was 9.1 (range, 6.2–22.0) months. The median number of treatment cycles was three (range, 2–11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.Conclusion Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.Trial registration number and date of registrationUMIN000010739, May 16, 2013, retrospectively registered

scholarly journals Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653)

2019 ◽  
Vol 37 (29) ◽  
pp. 2682-2688 ◽  
Author(s):  
Sarmad Sadeghi ◽  
Susan G. Groshen ◽  
Denice D. Tsao-Wei ◽  
Rahul Parikh ◽  
Amir Mortazavi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Median Number ◽  
Final Report ◽  
Curative Surgery ◽  
Metastatic Urothelial Carcinoma

PURPOSE Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program–sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated

3595 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with fluoropyrimidines-, oxaliplatin- and irinotecan-containing regimens. Methods: 36 pts were enrolled, with the following characteristics: 19 females (53%), median age 57 (28-72), 30 EOGO PS 0-1 (83%). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was 5 (range 1-9), ORR was 16.7% (95% confidence interval [CI] 4.5-28.9%) and disease control rate was 61.1% (95% CI 45.2-77.0%) with 6 partial responses and 16 stable diseases. Median duration of disease control was 5.8 months (95% CI 4.1-7.5 months). Median progression-free survival was 3.7 months (95% CI 2.2-5.2 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Grade 3-4 toxicities were rare (neutropenia 12%, anemia 11%, leucopenia 6%, thrombocytopenia 3% and diarrhea 3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was a convenient, well tolerated and efficacious for heavily pre-treated pts with mCRC. This regimen warrants further evaluation in pts with good PS but no further treatment options.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

A phase II study of the halichondrin B analog, E7389, in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. A California Consortium/University of Pittsburgh/University of Chicago NCI/CTEP sponsored trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8056-8056
Author(s):  
B. J. Gitlitz ◽  
A. M. Davies ◽  
C. P. Belani ◽  
A. Argiris ◽  
S. S. Ramalingam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Median Number ◽  
Disease Rate ◽  
Hematologic Toxicity ◽  
Halichondrin B ◽  
Grade 3

8056 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of halichondrin B and has a unique mechanism of microtubule binding and interaction, distinct from other agents in this class. Thus, it was our hypothesis that pts with prior taxane based therapy would respond to this agent. We conducted a phase II trial of E7389 in prior taxane-treated NSCLC pts. Methods: Eligible pts included: histologically confirmed advanced NSCLC, previous treatment with platinum-based therapy and a taxane, no more than 2 prior regimens, measurable disease, Zubrod performance status ≤ 2. Pts were classified by taxane-sensitivity status: taxane sensitive (TS) (progression >90 days after taxane) or taxane resistant (TR) (progression during or ≤90 days after taxane). Treatment: E7389 1.4 mg/m2 intravenously over 1–2 minutes on day 1 and 8 of a 21 day schedule until disease progression or unacceptable toxicity. Results: 41 pts were entered. There were 3 (15%) objective responses (7.2+, 8.5+, 10.6 mo) of 20 TS pts; and no response of 21 TR pts. Stable disease rate was 60% and 24% in TS and TR pts. respectively. Median progression free survival (PFS) is 6.3 mos TS pts. 95%CI (2.5–8.6 mos) and 1.2 mos TR pts. 95%CI (1.1–4.1 mos). Median number of cycles (range): TS 4 (1–14); TR 2 (1–7). Major toxicity included: 19 pts (46%) with grade 3 or 4 hematologic toxicity including only 1 episode of febrile neutropenia and 8 pts (20%) with grade 3 or 4 non-hematologic toxicity attributable to drug including: fatigue (1), dehydration (2), nausea (2), constipation (2). Only 1 pt developed grade 3 neuropathy (course 9). Conclusions: E7389 was well tolerated with encouraging objective response, PFS and disease control rate in the TS cohort. This cohort will be expanded, using a 2-stage design, to accrue up to another 25 pts. No significant financial relationships to disclose.

Weekly docetaxel and cisplatin with capecitabine and bevacizumab (AVDCX) in patients with advanced esophagogastric cancer: Results of a phase Ib/II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15078-e15078
Author(s):  
Ofer Purim ◽  
Yulia Kundel ◽  
Udi Sadeh Gonik ◽  
Efraim Idelevich ◽  
Gal Medalia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Ib ◽  
Weekly Docetaxel ◽  
Esophagogastric Cancer ◽  
Dose Levels

e15078 Background: Many efforts are being made to improve treatment options for advanced esophagogastric cancer (AEGC). The aim of this phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. Methods: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). To assure regimen's safety a short phase Ib part, with three dose levels, was planned. The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX and to determine the tumor response rate. Results: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%) and these were usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. Eventually, the recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). The objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. Eighteen patients (82%) derived a clinical benefit: improvement of pain, weight or performance status without a deterioration of any of these factors, from treatment. The median overall survival was 11.3 months (range, 1.5-39.2+ months) and median progression-free survival was 8.7 months (range, 1.3–26.6 months). The 2-year OS rate reached 22.7%. Conclusions: AVDCX was associated with bevacizumab-related fatal toxicities. It seems to reproduce the efficacy of bevacizumab regimen AVAGAST trial, without a clue for significant improvement over common docetaxel regimens in AEGC.

A phase II trial of nintedanib in recurrent malignant pleural mesothelioma (MPM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20061-e20061
Author(s):  
Antoinette J. Wozniak ◽  
Bryan J. Schneider ◽  
Gregory Peter Kalemkerian ◽  
Robert Michael Daly ◽  
Wei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Unmet Need ◽  
Small Subset ◽  
Pleural Mesothelioma ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e20061 Background: Malignant pleural mesothelioma (MPM) is a disease that is resistant to chemotherapy and there remains an unmet need for better therapeutic options. Nintedanib (BIBF 1120) is an oral multikinase inhibitor impacting VEGFR, FGFR, PDGFR, and other kinase activity such as TGFß signaling pathways. VEGF, FGF, and TGFβ are commonly expressed in MPM. We conducted a phase II trial in patients with recurrent MPM after platinum-based chemotherapy. Methods: Patients (pts) with MPM previously treated with platinum-based chemotherapy, performance status (PS) 0-1, adequate organ function, and no contraindications to anti-angiogenic therapy were eligible for treatment. Nintedanib 200 mg twice per day was administered until disease progression or unacceptable toxicity. The primary endpoint was the 4-month progression-free survival (PFS). A two-stage design was used and > 4 pts had to have a PFS of ≥4 months to proceed to the second stage. Results: Twenty pts. were enrolled. The median age was 70 yrs. (32-81), 90% were male, and 80% were PS = 1. The histology was 70% epithelioidal, 5% sarcomatoid, 10% biphasic, and 15% unknown. 15% had prior bevacizumab. The median follow-up is 16.4 mo. A median of 2 treatment cycles (range 1-18) were delivered. There were no responses but 40% had stable disease. The median PFS was 1.8 mo. (95% CI: 1.68, 3.55) and the PFS rate at 4 mo. was 13%. The median OS was 4.2 mo. (95% CI: 2.53, 8.74) and the OS rate at 4 mo. was 55%. Toxicities were usually grade 1-2 and included diarrhea, fatigue, edema, transaminase elevation, anorexia, nausea, vomiting and dyspnea. Conclusions: The activity of nintedanib in previously treated MPM pts. was modest. The trial did not meet the primary PFS endpoint. However, there was a small subset of pts. that had prolonged stable disease for > 4 months thus potentially deriving some clinical benefit from treatment. Supported by Boehringer Ingelheim. Clinical trial information: NCT02568449.

Phase II study of amrubicin for previously treated patients with malignant pleural mesothelioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21095-e21095
Author(s):  
Kazumasa Akagi ◽  
Takaya Ikeda ◽  
Katsumi Nakatomi ◽  
Hirokazu Taniguchi ◽  
Midori Shimada ◽  
...  
Keyword(s):  
Survival Time ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Phase Ii Study ◽  
Performance Status ◽  
Pleural Mesothelioma ◽  
Line Treatment ◽  
Second Line ◽  
Previously Treated Patients ◽  
Previously Treated

e21095 Background: Malignant pleural mesothelioma (MPM) is a rare disease with few effective treatments and poor prognosis. Although pemetrexed (PEM) and cisplatin for the first-line treatment, and nivolumab for the second-line are considered as the standard treatment for patients with unresectable disease, these effects are still limited. There are no other effective agents for second-line treatment, although PEM-based regimens, vinorelbine, gemcitabine are recommended by some guidelines. Novel therapeutic strategies for the treatment of MPM are urgently required. Amrubicin (AMR) is a chemically synthesized anthracycline-based anticancer drug that inhibits cell growth by stabilizing the cleavable complex via topoisomerase II. The same anthracycline; adriamycin was one of the key drugs for MPM prior to the appearance of PEM, but its efficacy against MPM has not been revealed. Thus, we planned a phase II study of AMR therapy for previously treated MPM. Methods: Eligibility criteria were previously treated patients with unresectable MPM, performance status 0-2, age≦75, and adequate hematological, hepatic and renal function. Patients were treated with injections of AMR 35 mg/m2 on days 1, 2, and 3. The treatments were repeated every 3-4 weeks. The primary endpoint was the response rate (RR), the secondary endpoints were safety, progression-free survival time (PFS), overall survival time (OS). Results: Although the number of target cases was 32 cases, case registration was delayed and evaluation was performed with 10 cases enrolled. Patients' characteristics were as follows: male/female = 9/1; performance status 0/1/2 = 0/10/0; median age (range) = 67 (49-73); histology epithelial/sarcomatoid/mixed = 4/3/3; stage (IMIG) I/II/III/IV/postoperative recurrence = 0/1/4/4/1. RR was 10.0% (1/10), median PFS was 1.6 months and median OS was 6.6 months. Disease control rate was 50.0% (5/10). Adverse events of Grade 3 or 4 were neutropenia 60.0% (6/10), thrombocytopenia 10.0% (1/10), anemia 10.0% (1/10), febrile neutropenia 10.0% (1/10), and pneumonia 10.0% (1/10). Conclusions: This study demonstrated that AMR therapy for previously treated MPM was tolerable. The efficacy was limited, but may be effective in some cases. Clinical trial information: UMIN000006381 .

Efficacy and safety of continuous daily sunitinib dosing in previously treated advanced non-small cell lung cancer (NSCLC): Results from a phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7542-7542 ◽  
Author(s):  
J. R. Brahmer ◽  
R. Govindan ◽  
S. Novello ◽  
R. Rosell ◽  
C. P. Belani ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Mucosal Inflammation ◽  
Previously Treated ◽  
Ecog Ps ◽  
Continuous Dosing

7542 Background: Sunitinib malate (SU), an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, has demonstrated activity in recurrent advanced NSCLC on the 4/2 schedule (4 weeks [wks] on treatment followed by 2 wks off), with a partial response (PR) rate of 11% (Socinski, ESMO 2006). A continuous dosing (CD) schedule of SU was additionally evaluated for safety and efficacy in this multicenter phase II study. Methods: Eligible patients (pts) had stage IIIB/IV NSCLC previously treated with 1–2 chemotherapy regimens, ECOG PS =1, and adequate organ function. Pts with brain metastases or recent gross hemoptysis were excluded. Pts received oral SU 37.5 mg/day continuously in 4-wk cycles. The primary endpoint was objective response rate per RECIST. Secondary endpoints included progression-free survival (PFS), overall survival, and safety. Results: Forty-seven pts were treated on the CD schedule: median age 60 yrs (range 37–81); male 57%; ECOG PS 0/1/2 49%/49%/2%; adenocarcinoma 53%, squamous cell carcinoma 15%, other 32%; median number of SU cycles initiated: 3 (range 1–10). One pt (2%) had a confirmed PR and 8 pts (17%) had stable disease >3 months. Median PFS was 12.1 wks (95% CI: 8.6–13.7). SU was generally well tolerated; most adverse events (AEs) were grade 1/2 and included fatigue/asthenia, pain/myalgia, nausea/vomiting, diarrhea, dyspnea, and stomatitis/mucosal inflammation. Grade =3 AEs included fatigue/asthenia (15%), hypertension (6%), hypoxia (6%), dyspnea (4%), and hemoptysis (2%). Treatment-related serious AEs included congestive heart failure (CHF; 1 pt), gastrointestinal bleeding (1 pt), hypomagnesemia (1 pt), and hypoxic respiratory failure (1 pt). One pt died due to possible treatment-related CHF. Conclusions: SU on a CD schedule is associated with an acceptable safety profile when administered to previously treated NSCLC pts, and there is documented preliminary evidence of activity, with 1 PR and a median PFS of 12.1 wks. These data support further study of continuous dosing of SU in combination with other treatments for NSCLC. No significant financial relationships to disclose.

Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

2021 ◽  
pp. 1-2
Author(s):  
Sarah Matz
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy Analysis ◽  
Duration Of Response ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

<b>Purpose:</b> Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. <b>Methods:</b> Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. <b>Results:</b> At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. <b>Conclusion:</b> Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. <b>Trial registration:</b> ClinicalTrials.gov NCT02501096.

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