Apatinib plus paclitaxel versus placebo plus paclitaxel as second-line therapy in patients with gastric cancer with peritoneal carcinomatosis: A double-blind, randomized phase II trial.

e16022 Background: Individuals with gastric cancer who present with peritoneal metastasis (PM) have poor prognosis. VEGF and VEGFR-2-mediated angiogenesis can increase vascular permeability, mesothelial cell permeability and promote peritoneal metastasis and ascites formation. This study assessed whether apatinib, a small-molecule VEGFR-2 tyrosine kinase inhibitor, in combination with paclitaxel would improve survival in patients with gastric cancer with PM as second-line therapy. Methods: This was a randomized, placebo-controlled, double-blind phase 2 trial. Recruitment of the trial was stopped after 44 patients due to poor accrual. Patients aged 18 years or older with gastric adenocarcinoma with PM and disease progression after first-line chemotherapy (platinum plus fluoropyrimidine) were randomly assigned in a 1:1 ratio to receive apatinib or placebo 500 mg oral once daily plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR) and safety profiles. Results: Between January 2017 and January 2019, 44 patients were randomly assigned to treatment (21 in Paclitaxel/apatinib group while 23 in Paclitaxel/placebo group). Median PFS was significantly longer in apatinib plus paclitaxel group than in placebo plus paclitaxel group (4.67 months [95% CI, 3.90 to 9.13 months] vs 4.07 months [95% CI, 1.93 to 5.00 months]; hazard ratio 0.46 [95% CI, 0.22 to 0.97]; P=0.037). There was no significant difference between the two groups in median OS (8.57 months vs. 9.03 months; P=0.85), ORR (19.0% vs. 4.3%; P=0.290) and DCR (76.2% vs. 52.2%, P=0.098). Apatinib group showed a higher incidence of proteinuria (38.1% vs. 4.3%; P=0.016), while no significant difference was found in the incidence of grade 3 or higher drug-related adverse events. Conclusions: Compared with placebo plus paclitaxel, the combination of apatinib with paclitaxel as second-line therapy significantly improved median PFS with an acceptable safety profile in patients with gastric cancer with peritoneal metastasis. Clinical trial information: NCT03144843. [Table: see text]

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HGCSG 1301: A multicenter, double-blind, randomized controlled phase II trial comparing Hange-shashin-to versus placebo to prevent diarrhea in patients with metastatic colorectal cancer treated with IRIS/Bev as second-line therapy—Updated analysis of antitumor efficacy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.108 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 108-108

Author(s):

Atsushi Ishiguro ◽

Hiroshi Nakatsumi ◽

Tetsuhito Muranaka ◽

Yasuyuki Kawamoto ◽

Satoshi Yuki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Progression Free Survival ◽

Controlled Study ◽

Second Line ◽

Second Line Therapy ◽

Double Blind ◽

Line Therapy ◽

Significant Difference ◽

Grade 3

108 Background: IRIS (irinotecan plus S-1) plus bevacizumab (IRIS/Bev) is one of the standard chemotherapies in Japan for metastatic colorectal cancer (mCRC) as the first-line or second-line therapy. The most frequent non-hematological adverse event of IRIS was diarrhea. Hange-shashin-to (HST) is a Kampo medicine which is used in Japan for the treatment of gastritis, stomatitis, and diarrhea. We conducted this study to evaluate the usefulness of HST to prevent diarrhea in patients with mCRC receiving IRIS/Bev as the second-line therapy. Methods: This trial was designed as a multicenter, randomized, double-blind, placebo-controlled study. We administrated HST 2.5g or placebo PO t.i.d. x 3 months from the first treatment course of IRIS/Bev. The primary endpoint is proportion of ≥grade 3 diarrhea assessed by CTCAE v4.0. This study is registered with UMIN-CTR, number UMIN000012276. Results: Between Jan 1, 2014 and Mar 31, 2017, 59 patients from 11 institutes in Japan were randomly assigned to receive HST (n = 28, Group H) or placebo (n = 29, Group P). The proportions of ≥grade 3 diarrhea was 10.7% in Group H and 13.8% in Group P (p = 1.00). The other major adverse events of ≥grade 3 in Group H vs Group P were fatigue (3.6% vs 10.3%), anorexia (14.3% vs 10.3%), and nausea (0.0% vs 3.4%). The overall response rate was 13.6% in Group H vs 7.7% in Group P (p = 0.65). There were not statistically significant differences in median progression-free survival (mPFS), median time to treatment failure (mTTF), and median overall survival (mOS) between Group H and Group P ( mPFS 7.9 vs 5.9 months; p = 0.35; mTTF 3.8 vs 5.6; p = 0.466; mOS 17.0 vs 15.3 months; p = 0.750). Conclusions: Prophylactic HST could not reduce the severity of diarrhea during IRIS/Bev. The update analysis of anti-tumor efficacy showed that IRIS/Bev had promising survival benefit but there is not statistically significant difference between HST and placebo. Clinical trial information: UMIN000012276.

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.20.00947 ◽

2021 ◽

Vol 39 (2) ◽

pp. 107-115

Author(s):

Paul J. Bröckelmann ◽

Horst Müller ◽

Teresa Guhl ◽

Karolin Behringer ◽

Michael Fuchs ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Early Stage ◽

High Dose Chemotherapy ◽

Sensitivity Analyses ◽

High Dose ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Significant Difference ◽

First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

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1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1520 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S680-S681

Author(s):

Carly Heck ◽

Judith Martin ◽

Marcia Kurs-Lasky

Keyword(s):

Drug Allergy ◽

Health Concern ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Comparison Results ◽

Significant Difference ◽

Recommended Therapy

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures

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Determining the efficiency of the Imatinib mesylate and monitoring of relapse and emergence of IM resistance in Algerian adult patients with Chronic Myeloid Leukaemia

South Asian Journal of Experimental Biology ◽

10.38150/sajeb.8(3).p103-108 ◽

2019 ◽

Vol 8 (3) ◽

pp. 103-108

Author(s):

Amel Sebaa ◽

Mustapha Diaf ◽

Sakina Cherif Touil

Keyword(s):

Chronic Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Imatinib Mesylate ◽

Second Generation ◽

Adult Patients ◽

Second Line ◽

Second Line Therapy ◽

Molecular Responses ◽

Line Therapy ◽

Significant Difference

Imatinib mesylate (IM) shows remarkable clinical activity in patients with Chronic Myeloid Leukaemia (CML). Patients who fail to respond to IM or those who lose their response should be treated with second-generation tyrosine kinase inhibitors (TKIs). The aim of this study was to determine the efficiency of the Indian IM generic (Imatib*CIPLA), and to monitor relapse and emergence of IM resistance. Two hundred and seven adult patients from the Northwestern region of Algeria were diagnosed as CML in chronic phase (CP) and were treated with an Indian generic of IM at 400 mg/day. The IM 600 mg treatment and second-line therapy were prescribed after failure of treatment. Molecular Analysis was performed and BCR-ABL/ABL ratios were determined and standardised according to the international scale using 0.47 as conversion factor. Our findings showed a significant difference in major molecular response (MMR) for patients treated with IM 600 mg compared to IM 400 mg (51.7% vs. 37.6%, p<0.001). In the second line therapy group, there was a significant improvement of MR4.5 compared to the IM group (7.7% vs. 32.6%, p=0.039). Likewise, no significant relationship was found between the median duration of second-generation TKIs deep response and IM 400 mg/day regarding the MR4 (11 vs. 26.5 months, p=0.107) and MR4.5 (20 vs. 32.5 months, p=0.203). The Indian IM generic molecule (Imatib*CIPLA), has shown its efficiency in achieving major and deep molecular responses. Patients treated with the second-generation TKIs showed deep molecular responses with fewer relapses in a shorter median time than those treated with IM.

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Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer

Cancer ◽

10.1002/cncr.31552 ◽

2018 ◽

Vol 124 (15) ◽

pp. 3118-3126 ◽

Cited By ~ 10

Author(s):

Hanna K. Sanoff ◽

Richard M. Goldberg ◽

Anastasia Ivanova ◽

Seamus O'Reilly ◽

Samer S. Kasbari ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Second Line ◽

Phase 2 ◽

Second Line Therapy ◽

Double Blind ◽

Phase 2 Trial ◽

Line Therapy

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A randomized double-blind phase 2 study of ruxolitinib (RUX) or placebo (PBO) with capecitabine (CAPE) as second-line therapy in patients (pts) with metastatic pancreatic cancer (mPC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.4000 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 4000-4000 ◽

Cited By ~ 18

Author(s):

Herbert Hurwitz ◽

Nikhil Uppal ◽

Stephanie Ann Wagner ◽

Johanna C. Bendell ◽

J. Thaddeus Beck ◽

...

Keyword(s):

Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Second Line ◽

Phase 2 ◽

Second Line Therapy ◽

Double Blind ◽

Line Therapy ◽

Phase 2 Study

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Prognostic factors in 868 advanced gastric cancer patients exposed to second-line therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e15553 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e15553-e15553

Author(s):

Valentina Fanotto ◽

Caterina Fontanella ◽

Mario Uccello ◽

Giulia Pasquini ◽

Silvia Bozzarelli ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Gastric Cancer Patients

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Cost-effectiveness analysis of pressurized intraperitoneal aerosol chemotherapy (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.387 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 387-387

Author(s):

Mehdi Javanbakht ◽

Mohsen Yaghoubi ◽

Atefeh Mashayekhi ◽

Philipp Horvath ◽

Alfred Koenigsrainer ◽

...

Keyword(s):

Gastric Cancer ◽

Cost Effectiveness ◽

Palliative Chemotherapy ◽

Cost Effective ◽

Dominant Strategy ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Upfront Therapy ◽

Line Chemotherapy

387 Background: The efficacy of systemic chemotherapy is still highly unsatisfactory for patients with gastric cancer and peritoneal metastases (PM). The aim of this study was to assess the costs effectiveness of pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) for advanced gastric cancer. Methods: We developed a state transition Markov Model to estimate the costs and effectiveness of the use of PIPAC C/D versus palliative chemotherapy. Intervention was assessed in two different levels including upfront therapy (PIPAC C/D plus XELOX chemotherapy versus first-line chemotherapy alone) and second line therapy (PIPAC C/D only versus second-line chemotherapy (ramucirumab monotherapy)). Data from multiple sources such as published literature and UK-based databases were used to inform the economic model. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of key parameter variation on the results. Results: For the upfront therapy the estimated total costs in the intervention and comparator arms were £33,587(SD: £2,394) and £17,477 (£927) respectively. PIPAC C/D plus XELOX led to an increase of 0.56 in QALYs. Estimated incremental cost per quality adjusted life years (QALYs) was £28,879. Result from probabilistic sensitivity analysis showed that PIPAC C/D plus XELOX is cost effective in more than 50% of Monte Carlo simulations at £30,000 threshold. For the second-line therapy, the total costs for PIPAC C/D was £15,985 (£1,391) and for the second-line palliative chemotherapy was £36,319 (£3,673). PIPAC C/D led to an increase of 0.21 in QALYs and £20,222 reduction in costs, meaning the intervention is dominant strategy in the second line therapy as it is less costly and more effective. Conclusions: The cost effectiveness results for the upfront therapy indicate that PIPAC C/D plus chemotherapy intervention is more costly and more effective and a cost effective intervention. PIPAC C/D only intervention has the potential to reduce costs and improve clinical outcomes for patients with advanced gastric cancer with peritoneal metastasis and therefore a dominant strategy.

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