Effect of weekly administration of bevacizumab, eribulin, and oxalilplatin in patients with heavily pretreated serous ovarian carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16506-e16506 ◽  
Author(s):  
Yuji Ikeda ◽  
Masashi Takano ◽  
Naoki Sasaki ◽  
Tsunekazu Kita ◽  
Yoshihiro Kikuchi ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Gynecologic Cancer ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Activity ◽  
Weekly Administration ◽  
Serous Ovarian Carcinoma ◽  
Heavily Pretreated ◽  
Grade 3

e16506 Background: Eribulin, inhibiting a protein component of tubulin, extend the lifespan of patients with late-stage breast cancer who are not benefiting paclitaxel. Bevacizumab (B) is known to enhance chemotherapeutic efficacy of platinum agents. We evaluated the effect of weekly administration of B with eribulin and oxaliplatin (EriOX) in recurrent or refractory serous ovarian carcinoma patients (ROC) pretreated with paclitaxel and carboplatin. Methods: Thirteen patients with ROC had treated with weekly-B and EriOX consisting of B (2mg/kg), eribulin (1mg/m2) and oxaliplatin (30mg/m2). The response and adverse effects (AE) were evaluated using the response evaluation criteria in solid tumors (RECIST), CA125 Gynecologic Cancer Intergroup (GCIG) criteria, and common terminology criteria for adverse events (CTCAE) version 4.0. Results: One patient is still under treatment of two cycles. We evaluated 12 patients at least two or more cycles of weekly B and EriOX. Ten patients (83%) were primarily stage 3 or 4. Ten patients (83%) had received three or more regimens of chemotherapy. All patients were pretreated with paclitaxel and carboplatin and 9 patients (75%) had been pretreated with platinum containing regimen within 6 months. According to the RECIST evaluation, 2 patients (17%) had a complete response (CR), 1 patient (8%) had a partial remission (PR) and 3 patients (25%) had a stable disease (SD). The response rate (CR+PR) and clinical benefit rate (CR+PR+SD) were 25% and 50%, respectively. Median progression-free survival was 3 months (range: 1-5 months). Hematological AEs with grade 3/4 were observed in 2 patients (17%). Hypo albuminemia and edema with grade 3 were in 1 patient (8%), respectively. However, all AE were manageable and torelable. Conclusions: Weekly B and EriOX administration had significant activity with mild AE in patients with paclitaxel and platinum resistant ROC. These results warrant further prospective study.

Effect of weekly administration of bevacizumab, gemcitabine, and oxaliplatin in patients with heavily pretreated ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5037-5037 ◽  
Author(s):  
Yuji Ikeda ◽  
Yoshihiro Kikuchi ◽  
Masashi Takano ◽  
Tomoko Goto ◽  
Hiroko Kouta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Effects ◽  
Gynecologic Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Activity ◽  
Serous Adenocarcinoma ◽  
Weekly Administration ◽  
Heavily Pretreated

5037 Background: The combination therapy of gemcitabine with oxaliplatin (GEMOX) has high activity in patients with ovarian cancer. Bevacizumab (B), a vascular endothelial growth factor specific antibody, enhances chemotherapeutic efficacy through its anti-angiogenic function in various types of tumors. We evaluated the effect of weekly administration of B and GEMOX in heavily-pretreated patients with recurrent or refractory ovarian cancers (ROC). Methods: Nineteen patients with ROC received at least three or more cycles of weekly-B and GEMOX consisting of B (2mg/kg), gemcitabine (300mg/m2) and oxaliplatin (30mg/m2). The treatment was continued until the development of progressive disease. The response and adverse effects (AE) were evaluated using the response evaluation criteria in solid tumors (RECIST), CA125 Gynecologic Cancer Intergroup (GCIG) criteria, and common terminology criteria for adverse events (CTCAE) version 3.0. Results: Seventeen (89%) of the 19 patients were primarily stage 3 or 4. Fifteen patients (79%) had received more than three regimens of chemotherapy. All patients were pretreated with a platinum-containing regimen within 6 months and 16 of these patients (84%) were pretreated within 3 months. According to the RECIST evaluation, 2 patients (11%) had a complete response (CR), 6 patients (32%) had a partial remission (PR) and 5 patients (26%) had a stable disease (SD). The response rate (RR; CR+PR) and clinical benefit rate (CBR; CR+PR+SD) were 42% and 68%, respectively. In 10 patients with serous adenocarcinoma, RR was 60%. In 6 patients pretreated with weekly B and pegylated liposomal doxorubicin (PLD), RR was 50%. Median progression-free survival was 5 months (range: 2-11 months). Hematological adverse effects (AE) with grade 3/4 were leukopenia (16%), neutropenia (10%), thrombocytopenia (5%), however, all AE were manageable. Conclusions: Weekly B and GEMOX administration had significant activity with mild AE in patients with ROC especially in serous adenocarcinoma. Notably, the activity was also observed in patients pretreated with weekly B and PLD. These results warrant further prospective study.

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

Effects of temozolomide and bevacizumab in relapsed patients with heavily pretreated uterine leiomyosarcoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11056-11056
Author(s):  
Hiroko Matsuura ◽  
Sayaka Ikeda ◽  
Kazuya Kudoh ◽  
Naoki Sasaki ◽  
Masashi Takano ◽  
...  
Keyword(s):  
Response Rate ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Uterine Leiomyosarcoma ◽  
Response Evaluation ◽  
Free Survival ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Derivatives Of

11056 Background: Uterine leiomyosarcomas (ULMs) tend to recur regardless of their stage, and there is no satisfactory report for relapsed ULMs. Temozolomide (T) is derivatives of dacarbazin and these agents have been used for treatment of ULMs. ULMs has a plenty of vessels compared to uterine myoma so that bevacizumab (B) was used in ULMs. In the present study, we evaluated the effect of TB in heavily pretreated relapsed ULMs. Methods: From 2009 to 2016, total 19 patients (pts) with heavily pretreated ULMs were enrolled. Patients were treated with T (80mg/body/day) and B (2mg/kg; days 1, 8 and 15, q4 weeks). Treatment was continued until disease progression and/or unmanageable toxicities. Response was evaluated with the response evaluation criteria in solid tumors (RECIST) v1.1, and adverse effect (AE) was assessed by common terminology criteria for adverse events (CTCAE) v4.0. Results: Seventeen of 19 pts were subjected to response evaluation. Median age of pts was 56.3 years (range: 31-69). Three pts (18%) had complete response (CR), 2 (12%) had partial response, and 7 (41%) had stable disease (SD). The response rate (RR: CR+PR) and clinical benefit rate (CBR: CR+PR+SD) were 29% and 71%. The median progression-free survival was 14.2 months (range: 0-89). Median administration cycle was 9.5 (range: 2-48). AE with grade 3 and more over were observed in 6 pts. There was one dead case from perforation, but toxicity was almost manageable. Conclusions: We experienced 3 cases of CR, and two of them had CR for more than two years. Intriguingly, TB could be substantially effective even in relapsed patients with heavily pretreated ULMs. These results warrant further prospective and randomized studies.

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 .

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

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

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

Pomalidomide Cyclophosphamide and Prednisone (PCP) Treatment for Relapsed/Refractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 446-446 ◽  
Author(s):  
Antonio Palumbo ◽  
Alessandra Larocca ◽  
Vittorio Montefusco ◽  
Davide Rossi ◽  
Angelo Michele Carella ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Advisory Committees ◽  
Free Survival ◽  
Significant Toxicity ◽  
Grade 3 ◽  
Clinical Conditions

Abstract Abstract 446 Background: The outcome of myeloma (MM) patients who are no longer responding to thalidomide, lenalidomide or bortezomib is poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months (Kumar SK et al, Leukemia 2012). The newer immunomodulatory drug pomalidomide, has shown significant activity in these clinical conditions. Aims: We assessed dosing, efficacy and safety of pomalidomide-cyclophosphamide-prednisone (PCP) in MM patients relapsed/refractory to lenalidomide. Methods: Pomalidomide was administered in doses ranging from 1 to 2.5 mg/day on days 1–28, cyclophosphamide at 50 mg every other day on days 1–28 and prednisone at 50 mg every other day on days 1–28 for 6 cycles, followed by maintenance therapy with pomalidomide-prednisone. Thromboprophylaxis with aspirin 100 mg/day or low-molecular weight heparin was recommended at physician's discretion. Results: The maximum tolerated dose (MTD) of pomalidomide was defined as 2.5 mg/day. Fifty-two patients were enrolled at the MTD and evaluated after completing at least 1 PCP cycle. Median age was 69 years (range 41–83). The median time from diagnosis to enrolment was 55 months (range 15–203). Best responses to PCP included 6% of complete response (CR), 19% of at least very good partial response (VGPR), 54% of at least partial response (PR) and 75% of at least minimal response (MR). Time to PR was rapid (median 1.8 months). After a median follow-up of 11 months (range 1–18), 1-year progression-free survival (PFS) and OS rates were 52% and 78%, respectively. PFS was not significantly different in patients with high-risk cytogenetic compared with patients with standard-risk disease and in patients younger or older than 75 years. Toxicities were primarily hematologic and included grade 4 neutropenia (13%) and thrombocytopenia (4%). At least grade 3 non-hematologic toxicities included infections (8%), rash (6%) and neurologic (6%). Thromboembolism occurred in 1 patient. Four patients discontinued treatment for toxicity (2 infections, 1 neurologic and 1 hepatic toxicity). Conclusions: PCP induced high response rates and prolonged PFS after prior exposure to lenalidomide and bortezomib (Table), without adding significant toxicity. PCP could be considered a valuable salvage option for pre-treated MM patients. Disclosures: Palumbo: Celgene: Consultancy, Honoraria. Larocca:Celgene: Honoraria. Sciacca:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Guglielmelli:Celgene: Honoraria. Giuliani:Celgene: Research Funding. Boccadoro:Celgene: Consultancy, Honoraria.

Effectiveness of weekly topotecan in patients with recurrent epithelial ovarian cancer

2007 ◽  
Vol 17 (1) ◽  
pp. 83-87 ◽  
Author(s):  
I. Vandenput ◽  
F. Amant ◽  
P. Neven ◽  
P. Berteloot ◽  
K. Leunen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Dose Reduction ◽  
Response Rate ◽  
Gynecologic Cancer ◽  
Complete Response ◽  
Bone Marrow Toxicity ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

The objective of this study was to investigate the effectiveness and toxicity of weekly topotecan in patients with recurrent epithelial ovarian cancer. Twenty patients were treated with topotecan at a dose of 4 mg/m2weekly. Efficacy was determined according to the Response Criteria in Solid Tumors (RECIST) Gynecologic Cancer Inter Group criteria. Median age was 62 years (45–78). Patients had received 1–7 (median 3) prior chemotherapy lines. A total of 203 weekly treatments were administered. In 13 patients (65%) treatment delay was necessary due to bone marrow toxicity. Grade 3/4 neutropenia occurred in 11 patients (55%) and grade 3/4 thrombocytopenia in four patients (20%). Six patients (30%) needed a dose reduction, and 42 cycles (21%) were given with dose reduction. No neutropenia, fever, or sepsis was observed. There was one complete response and one partial response (response rate 10%). All patients with response had platin-sensitive disease (three out of eight). Six patients needed blood transfusion. None of the patients required granulocyte/granulocyte-macrophage colony-stimulating factor. The median duration of response was 13 months. In addition, there were four patients (20%) with a stable disease lasting at least for 4 months. Based on the results of this Phase II study, the toxicity of weekly topotecan seems to be lower than with the 3-weekly topotecan. The response rate of 10% is low but was not expected to be higher as these patients were heavily pretreated.

Combination chemotherapy of intraperitoneal carboplatin and intravenous paclitaxel in suboptimally debulked epithelial ovarian cancer

2008 ◽  
Vol 18 (6) ◽  
pp. 1210-1214 ◽  
Author(s):  
S. Nagao ◽  
K. Fujiwara ◽  
R. Ohishi ◽  
Y. Nakanishi ◽  
N. Iwasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Combination Chemotherapy ◽  
Progressive Disease ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Complete Response ◽  
Peritoneal Carcinoma ◽  
Free Survival ◽  
Grade 3

The objective of this study was to retrospectively assess the efficacy and safety of combination chemotherapy of intraperitoneal (IP) carboplatin and intravenous (IV) paclitaxel in suboptimally debulked ovarian cancer. Between March 1998 and March 2006, 44 patients with histologically confirmed epithelial ovarian carcinoma or peritoneal carcinoma with a residual mass greater than 1 cm received combination chemotherapy of IV paclitaxel and IP carboplatin. Administration of IV paclitaxel at 175 mg/m2 immediately followed by IP carboplatin at an area under the curve of 6 was scheduled every 3 weeks for at least six cycles. The diagnosis and stage were ovarian carcinoma stage II in 8, III in 25, and IV in 6 cases, and peritoneal carcinoma stage III in 5 cases. Eighty-three percent of patients completed more than six cycles of chemotherapy. The incidences of grade 3/4 hematologic toxicities were 41 (93%) for neutrocytopenia, 10 (41%) for thrombocytopenia, and 18 (23%) for anemia. Observed grade 3/4 nonhematologic toxicities were 1 (2%) for allergy, 1 (2%) for fatigue, 1 (2%) for vomiting, 1 (2%) for liver dysfunction, and 4 (9%) for peripheral neuropathy. Two patients (5%) encountered catheter problems (one obstruction and one infection). Overall response rate was 80% (16 complete response, 19 partial response, 3 stable disease, and 6 progressive disease). Median progression-free survival and overall survival were 24 and 31 months, respectively. Combination chemotherapy of IP carboplatin and IV paclitaxel is effective and safe in suboptimally debulked ovarian cancer, and further evaluation is warranted.

Results of a phase II study evaluating trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 48-48 ◽  
Author(s):  
Manish R. Patel ◽  
Gerald Steven Falchook ◽  
Kensuke Hamada ◽  
Lukas Makris ◽  
Robert E. Winkler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Additional Clinical Benefit

48 Background: Patients (pts) with colorectal cancer (CRC) with microsatellite instability (MSI) have recently been shown to respond to anti–programmed death (PD)-1 drugs. Preclinical data suggest that trifluridine/tipiracil (FTD/TPI) treatment converts MSS CRC cells to MSI, sensitizing them to the activity of anti–PD-1 drugs. The aim of this phase 2 study was to evaluate this hypothesis. Methods: This was a multicenter, single-arm, safety lead-in, phase 2 study that used Simon’s 2-stage design to evaluate the safety and efficacy of FTD/TPI (35 mg/m2 twice daily on days 1-5 and 8-12 every 28 days) plus nivolumab (3 mg/kg every 2 weeks) in pts with heavily pretreated MSS mCRC. Pts had histologically proven metastatic or locally advanced colorectal adenocarcinoma that was MSS (assessed by a local laboratory based on either previous or fresh biopsy), ≥1 measurable lesion for RECIST and immune-related response criteria (irRC) assessment, and failure of ≥2 previous lines of chemotherapy. Six pts were to be enrolled in the safety lead-in, and in order to proceed to Simon’s stage 2, ≥2 of the first 15 pts had to demonstrate a partial or complete response within 6 months based on irRC assessment. Results: The first 6 dose-limiting toxicity (DLT)-evaluable pts enrolled tolerated dosing with no DLTs. A total of 18 pretreated pts enrolled in the first stage (50% males; median age 56.5 yr), among whom 72% had colon cancer and 100% had MSS disease, 56% with RAS mutations. Pts received a median of 2.5 cycles of study therapy (range 1-8). The most common grade 3/4 adverse events (AEs) were neutropenia (28%); diarrhea (17%); and nausea, abdominal pain, fatigue, and anemia (11% each). No pts discontinued treatment due to AEs. No pts achieved a tumor response (either per RECIST or irRC), and the study did not progress to the second stage. Median (6-month) progression-free survival was 2.8 months (21%) per RECIST and 2.2 months (30%) per irRC. Conclusions: The combination of FTD/TPI and nivolumab was feasible and tolerated at the full dose of both compounds. Adding nivolumab to FTD/TPI did not provide additional clinical benefit in pts with previously treated MSS mCRC. Clinical trial information: NCT02860546.

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]

Sign in / Sign up

Export Citation Format

Share Document