Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Oncology ◽  
2020 ◽  
Vol 98 (11) ◽  
pp. 787-797 ◽  
Author(s):  
Yuwa Ando ◽  
Tomokazu Kawaoka ◽  
Yosuke Suehiro ◽  
Kenji Yamaoka ◽  
Yumi Kosaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Liver Function ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Class A ◽  
Line Therapy ◽  
Pugh Class ◽  
Ecog Ps

<b><i>Background:</i></b> Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. <b><i>Methods:</i></b> Patients (<i>n</i> = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. <b><i>Results:</i></b> One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: <i>n</i> = 26; ramucirumab: <i>n</i> = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, <i>p</i> = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (&#x3c;400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, <i>p</i> = 0.003), a relative tumor volume &#x3c;50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, <i>p</i> = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, <i>p</i> = 0.01) were significant prognostic factors. <b><i>Conclusion:</i></b> Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

Continued cetuximab in second-line treatment for patients with unresectable metastatic wild-type KRAS, NRAS, and BRAF colorectal cancer after disease progression during first-line cetuximab-based therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 127-127
Author(s):  
Ying Liu ◽  
Feng Wang ◽  
Ning Ma ◽  
Shuning Xu ◽  
Lei Qiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Line Chemotherapy

127 Background: Cetuximab plus chemotherapy is a first-line treatment option for metastatic RAS wild type colorectal cancer patients. Currently, no data are available on continuing cetuximab or changing bevacizumab as second-line therapy beyond first-line cetuximab-based chemotherapy. Methods: Patients (aged ≥18 years) with metastatic, histologically and genetically confirmed wild-type KRAS, NRAS and BRAF colorectal cancer progressing after first-line cetuximab plus chemotherapy were randomly assigned (1:1 ratio) to second-line chemotherapy with cetuximab (arm A) or with bevacizumab (arm B) 2·5 mg/kg per week equivalently. The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The second endpoint was overall survival (OS). Results: 77 Patients (from July 1, 2016 to Sept 20, 2019, 77) were randomized (41 in arm A and 36 in arm B). ORR was 29.3% and 19.4% in Arm A and Arm B ( p= 0.31). PFS was 7.2 months (95% CI 5.2–9.2) for Arm A and 5.9 months (95% CI 5.1–6.7) for Arm B ( p= 0.677). OS was 18.5 months (95% CI 15.1–21.8) for Arm A and 17.5 months (95% CI 15.4–19·7) for Arm B ( p= 0.444). Patients with ECOG PS 0 had significantly longer PFS and OS than ECOG PS 1 in second-line therapy whether cetuximab or bevacizumab combined with chemotherapy. ECOG 0 group vs ECOG 1 group, PFS was 8.7 months vs 4.6 months (p = 0.00) and OS was 21.2 months vs 12.3 months (p = 0.00). Moreover, ETS may predict efficacy of second-line continued cetuximab. The most frequently grade 3–4 adverse events in both arms were neutropenia (19.4% VS 16.7%), diarrhea (7.5% vs 11.1%), and nausea(10% vs 13.9%). Conclusions: Continuing cetuximab or changing bevacizumab plus standard second-line chemotherapy in patients with metastatic wild-type KRAS, NRAS and BRAF colorectal cancer after first-line cetuximab plus chemotherapy have similar clinical benefits. ECOG score is an independent predictor of prognosis and second-line treatment efficacy for colorectal cancer.

scholarly journals Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma

2020 ◽  
Vol 22 (3) ◽  
pp. 142-148
Author(s):  
L. V. Bolotina
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma ◽  
First Line Treatment

Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late disease intelligence does not frequently allow radical treatment, palliative methods remain the only option of survivability enhancement and improving the patients quality of life. Lenvatinib was approved as the first-line drug in the treatment of unresectable hepatocellular carcinoma based on the data of the REFLECT trial, in which the drug demonstrated achieving the patients overall survival (OS) comparable to the activity of sorafenib (13.6 months for lenvatinib vs 12.3 months for sorafenib; hazard ratio HR 0.92; 95% confidence interval CI 0.791.06). At the same time, significant inferiority of lenvatinib was observed for secondary endpoints: progression-free survival PFS (7.4 months for lenvatinib vs 3.7 months for sorafenib; HR 0.66; 95% CI 0.570.77;р0.0001), time to progression (8.9 months for lenvatinib vs 3.7 months for sorafenib; HR 0.63; 95% CI 0.530.73;р0.0001) and objective response rate ORR (24.1% for lenvatinib vs 9.2% for sorafenib). The further analysis of the results of the REFLECT study revealed the additional factors impacting patients survival, such as the level of a-fetoprotein (AFP) before treatment, treatment ORR, performance of subsequent antitumor therapy and procedures after completion of the target first-line therapy. In patients responding to lenvatinib in the first line and further receiving any second-line therapy, the mOS was 25.7 months as compared with the median overall survival (mOS) of 22.3 months in patients responding to sorafenib and receiving further second-line therapy. Additionally, in responders switching from lenvatinib to sorafenib, the mOS was 26.2 months. In the recently published comparative study of lenvatinib and transarterial chemoembolization on the BCLC B stage, inferiority of lenvatinib was demonstrated in terms of OS, PFS and ORR in certain patient categories. Considering the data obtained in the REFLECT population, where in patients achieving the RR to the first-line treatment with lenvatinib and further receiving the local antitumor procedures the mOS increased to 27.2 months (95% CI 20.729.8), prescribing target and locoregional therapy in certain cases in this very sequence is possible. The recently published data about administration of lenvatinib outside of the inclusion criteria for the REFLECT trial, have proved the efficacy and safety of this drug administration in real clinical practice, thus significantly expanding our understanding of the key role of lenvatinib in the first-line treatment of unresectable hepatocellular carcinoma.

scholarly journals Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update

2018 ◽  
Vol 36 (24) ◽  
pp. 2545-2556 ◽  
Author(s):  
Davendra P.S. Sohal ◽  
Erin B. Kennedy ◽  
Alok Khorana ◽  
Mehmet S. Copur ◽  
Christopher H. Crane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Ecog Ps ◽  
Comorbidity Profile

Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
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.

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

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

scholarly journals Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2773
Author(s):  
Marta Padovan ◽  
Marica Eoli ◽  
Alessia Pellerino ◽  
Simona Rizzato ◽  
Claudia Caserta ◽  
...  
Keyword(s):  
Real World ◽  
Recurrent Glioblastoma ◽  
Second Line ◽  
Ocular Toxicity ◽  
Phase 2 ◽  
Second Line Therapy ◽  
Italian Association ◽  
Phase 2 Trial ◽  
Line Therapy ◽  
Ecog Ps

Background: Depatuxizumab Mafodotin (Depatux-M; ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. Materials and Methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety. Results: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0–1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3–10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients; no grade 4 ocular toxicity was reported. No death was considered to be drug-related. Conclusions: The study reported the first “real world” experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 324-324
Author(s):  
Ciro Celsa ◽  
Giuseppe Cabibbo ◽  
Marco Enea ◽  
Salvatore Battaglia ◽  
Giacomo Emanuele Maria Rizzo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Data ◽  
Survival Curve ◽  
Second Line ◽  
First Line ◽  
Lifetime Horizon ◽  
First Line Therapy ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma ◽  
Sequential Strategy

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from Imbrave 150 trial and it was used as endpoint since it is not influenced by post-progression survival. For second-line retreatment, pooled OS of MKIs (Regorafenib and Cabozantinib), or ICIs (Nivolumab and Pembrolizumab) were adopted. Survival estimates for sequential settings considered the proportion of patients who did not receive second-line therapy due to death during first-line therapy. Individual patient survival data were extracted from PFS and OS Kaplan-Meier curves of RESORCE trial for Regorafenib, CELESTIAL trial for Cabozantinib, CheckMate-040 for Nivolumab and Keynote-240 for Pembrolizumab. Each reconstructed survival curve was inspected for accuracy and was compared with originally published curves. Results: First-line Atezolizumab plus Bevacizumab followed by second-line ICIs turned on from the model as the best sequential strategy (median s-OS 24 months; 95% Confidence Interval (CI) 23-26 months) and extends survival when compared Atezolizumab plus Bevacizumab followed by MKIs (median s-OS 20 months; 95% CI 19-21 months). Conclusions: To our knowledge and given the absence of adequately designed sequential RCTs, this is the first model to date which suggests, with a proper methodological approach, an accurate estimate of outcome of patients with u-HCC treated by sequential systemic therapies. In patients with u-HCC failing first-line treatment, modelling estimates of s-OS for each retreatment strategies may assist in choosing the most promising sequences in order to plan appropriate RCTs.

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