EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4681-TPS4681 ◽  
Author(s):  
Ian D. Davis ◽  
Val Gebski ◽  
Mark D. Chatfield ◽  
Peter S. Grimison ◽  
George Kannourakis ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Prognostic Score ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).

A double-blind, randomized placebo-controlled, phase II study of maintenance enzastaurin (ENZ) with 5-FU/leucovorin (LV) plus bevacizumab (BV) following first-line therapy for metastatic colorectal cancer (mCRC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
R. A. Wolff ◽  
W. Schepp ◽  
M. DiBartolomeo ◽  
A. Hossain ◽  
C. Stoffregen ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
First Line ◽  
Antitumor Effects ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

501 Background: Maintenance therapy is designed to maximize progression-free survival (PFS) and minimize toxicity in advanced CRC. ENZ is an oral serine/threonine kinase inhibitor that targets PKC-b and the AKT/PI3K pathway. Preclinical studies demonstrated synergistic antitumor effects when ENZ was combined with BV. In phase I studies, the combination was well tolerated. This phase II study assessed ENZ with 5-FU/LV plus BV as maintenance therapy for mCRC. Methods: Patients had locally advanced or mCRC, and completed 6 cycles of first-line chemotherapy ≤4 wks prior to randomization. Arm A received a loading dose of ENZ 1,125 mg, followed by 500 mg/d subsequent doses. Arm B received placebo. Both groups received 5-FU/LV (LV 400 mg/m2 IV, 5-FU 400 mg/m2 bolus, 5-FU 2,400 mg/m2 IV) plus BV 5 mg/kg IV, every 2 wks. Patients were treated with 5-FU/LV plus BV plus either ENZ or placebo until disease progression or for 1 yr. Primary endpoint was PFS from randomization. Secondary endpoints were overall survival (OS) from randomization, and OS and PFS from start of first-line therapy. Analysis was done after 50 events (objective or clinical progression). Results: 58 patients were randomized to Arm A (57 treated), 59 to Arm B (58 treated). 82 (70.1%) patients discontinued treatment (Arm A, 42 [72.4%]; Arm B, 40 [67.8%]), the majority due to disease progression. Median cycles were 9 in Arm A, 10 in Arm B. Median PFS in months was 5.8 in Arm A and 8.1 in Arm B (hazard ratio [HR]=1.35, 95% CI: 0.84, 2.16; protocol specified one-sided test, p=0.896). Median OS was not calculable due to high censoring (77.6% in Arm A and 91.5% in Arm B). Median PFS in months from start of first-line therapy was 8.9 in Arm A and 11.3 in Arm B (HR=1.39, 95% CI: 0.86, 2.23; one-sided, p=0.913). More patients developed thrombosis or embolism (TE), including pulmonary embolism, on Arm A (5 [8.8%] patients had grade 3 and 5 [8.8%] grade 4 TE) compared with Arm B (no grade 3 and 1 [1.7%] grade 4 TE). Conclusions: ENZ did not demonstrate an advantage in PFS compared to BV-based therapy alone. Further development of maintenance therapy with ENZ is not recommended for mCRC. [Table: see text]

Assessment for markers of poor prognosis in a real-world evidence study of treatment patterns in patients with HR+/HER2- locally advanced or metastatic breast cancer in Korea and Taiwan.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13083-e13083
Author(s):  
Diego Novick ◽  
Narayan Rajan ◽  
Rebecca Ming-Huei Cheng ◽  
Sae Young Lee ◽  
Dong Hyun Koo ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
First Line ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

e13083 Background: To assess how patient characteristics impact treatment patterns and real-world effectiveness among patients with hormone receptor (HR+)/human epidermal growth receptor 2-negative (HER2-) locally advanced and metastatic breast cancer (ABC) in Korea and Taiwan. Methods: We conducted a retrospective chart review comprising 227 female patients aged ≥ 18 years and diagnosed HR+/HER2- ABC in Korea and Taiwan between 2015-2017. Those having at least one of the following characteristics, shown previously to negatively impact prognosis, formed the poor prognostic cohort (PPC): ECOG PS > 0, not bone-only disease, liver metastases, or negative PgR status. Anonymized data on patient characteristics, treatment pathways, progression-free survival, and grade 3 or higher adverse events (AEs) of interest was abstracted. Descriptive statistics and Kaplan Meier methods were used to assess the outcomes. Results: The mean (range) age was 57.1 (29 - 83) years. A total of 193 (85.0%) patients were PPC. Endocrine regimens were the most frequent first-line therapies used by 50.3% and 67.6% of patients in the PPC and non-PPC cohorts, respectively. Chemotherapy regimens were used by 25.9% and 17.6% as initial systemic therapy and by 60.1% and 35.3% at any time following diagnosis of ABC, for PPC and non-PPC, respectively. The median progression-free survival time, based on first-line therapy, was 8.3 (95%CI: 6.9 – 10.4) months for PPC versus 11.5 (95%CI: 5.5 – 12.0) months in non-PPC. The proportion of patients with at least 1 grade 3 or higher AEs of interest during first-line therapy was higher in the PPC cohort compared to the non-PPC cohort, 54.4% vs. 44.1% respectively. The most common AEs reported were leukopenia, asthenia/fatigue and neutropenia occurring in 27.5%, 28.0% and 20.7% of the PPC cohort and 23.5%, 2.9%, and 14.7% of the non-PPC cohort, respectively. Conclusions: The existence of one or more poor prognostic factors is associated with a higher chemotherapy use any time following diagnosis of ABC, as well as lower median progression-free survival and a higher likelihood of having an adverse event during first line therapy, compared to non-PPC cohort. These results suggest that patient poor prognostic characteristics can be drivers for therapy selection.

Lenvatinib plus toripalimab as first-line treatment for advanced intrahepatic cholangiocarcinoma: A single-arm, phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4099-4099
Author(s):  
Zhou Jian ◽  
Jia Fan ◽  
Guo-Ming Shi ◽  
Xiao-Yong Huang ◽  
Dong Wu ◽  
...  
Keyword(s):  
Body Weight ◽  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

4099 Background: Lenvatinib monotherapy and lenvatinib plus PD-1 antibody have shown some clinical benefit for advanced intrahepatic cholangiocarcinoma (ICC) in the second-line setting. Our study assesses the role of lenvatinib plus toripalimab (PD-1 antibody) for advanced ICC patients as the first line therapy. Methods: Patients (pts) with locally advanced or metastatic ICC received 12 mg/day (Body Weight ≥60 kg) or 8 mg/day (Body Weight <60 kg) oral lenvatinib daily plus 240 mg intravenous toripalimab every 3 weeks. The primary endpoint was objective response rate (ORR) and evaluated according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Treatment continued until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. This trial is registered with ClinicalTrials.gov (NCT04361331). Results: From March 2020 to Sep. 2020, 31 pathologically confirmed advanced ICC pts with a mean age of 58.4 (range, 25-73) years, including 18 women (58.0%), were enrolled at Zhongshan Hospital, Fudan University. At the end of last follow-up (February 10, 2021), the ORR was 32.3% (10/31; 95% CI: 16.7%-51.4%) and the disease control rate (DCR) was 74.2% (23/31; 95% CI: 55.4%-88.1%). Median follow-up was 6.9 months. Two pts with locally advanced disease were down-staged and then underwent resection. They remained disease-free survival at the end of last follow-up. 11 pts exerted disease progression and 7 pts died. The median PFS and OS have not been reached. Median duration of response (DOR) has not been reached and responses were ongoing in 9/10 (90.0%) pts at data cutoff. 6-months OS rate was 87.1%. No grade 5 adverse event (AE) was observed in present study. 32.3% (10/31) of pts experienced Grade 3 or higher AEs and 1 pts discontinued the treatment owing to severe fatigue. Conclusions: As the first-line therapy, lenvatinib plus toripalimab provided promising efficacy with reasonable safety profile in advanced ICC patients. It offered an alternative treatment for advanced ICC who cannot tolerate gemcitabine-based chemotherapy. Clinical trial information: NCT04361331.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Disease Free Survival ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

Abstract Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

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