scholarly journals Targeting EGFR in Esophagogastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Steven B. Maron ◽  
James Xu ◽  
Yelena Y. Janjigian
Keyword(s):  
Overall Survival ◽  
Clinical Benefit ◽  
Routine Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Metastatic Setting ◽  
Esophagogastric Cancer ◽  
Phase Iii Trials ◽  
Related Mortality

Esophagogastric cancer (EGC) remains a major cause of cancer-related mortality. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to-date: only first line anti-HER2 therapy in ERBB2-expressing tumors, second line anti-VEGFR2 therapy with ramucirumab in unselected patients, and pembrolizumab in PD-L1 expressing or MSI-H patients. EGFR inhibitors were extensively studied in EGC, including phase III trials with cetuximab (EXPAND), panitumumab (REAL3), and gefitinib (COG). All three trials were conducted in unselected populations, and therefore, failed to demonstrate clinical benefit. Here, we review previous attempts at targeting EGFR in EGC and potential future biomarkers for targeting this pathway in patients with EGFR-amplified tumors.

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.

scholarly journals DERN CONTROL POINT INHIBITORS AND THEIR POSSIBILITIES FOR THE THERAPY OF METASTATIC UROTELIAL CANCER

2020 ◽  
Vol 6 (5(74)) ◽  
pp. 4-8
Author(s):  
M.N. Tillyashajhov ◽  
S.V. Kamyshov ◽  
E.V. Bojko
Keyword(s):  
Overall Survival ◽  
Control Point ◽  
Surface Protein ◽  
New Drugs ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Critical Question ◽  
Accelerated Approval ◽  
New Biomarkers

For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC). Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T‑lymphocytes PD‑1 and its ligands PD‑L1 and PD‑L2, resulting in the activation of the immune response. It is noteworthy that the anti‑PD‑1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA). Nivolumab (antibody PD‑1) also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD‑L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first‑line treatment in patients not receiving cisplatin). Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation.The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.

Irinotecan in the Treatment of Colorectal Cancer: Clinical Overview

2001 ◽  
Vol 19 (5) ◽  
pp. 1501-1518 ◽  
Author(s):  
Udo Vanhoefer ◽  
Andreas Harstrick ◽  
Wolf Achterrath ◽  
Shousong Cao ◽  
Siegfried Seeber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Topoisomerase I ◽  
Clinical Status ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase Iii Trials ◽  
Line Chemotherapy

PURPOSE AND METHODS: For more than three decades, the therapeutic options for patients with advanced colorectal cancer have almost exclusively been based on fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an important therapeutic target in cancer therapy, irinotecan, a semisynthetic TOP-I–interactive camptothecin derivative, has been clinically established in the treatment of colorectal cancer. RESULTS: Irinotecan was investigated as second-line chemotherapy after prior treatment with fluorouracil (FU)-based regimens in two large randomized phase III trials comparing irinotecan with either best supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of these trials established irinotecan as the standard therapy in the second-line treatment of colorectal cancer. The therapeutic value of irinotecan in the first-line treatment of metastatic colorectal cancer was investigated in two large randomized phase III trials comparing the combination of irinotecan and FU/LV with FU/LV alone. Both trials demonstrated significant superior efficacy for the combination of irinotecan and FU/LV in terms of response rate, median time to disease progression, and median survival time. Consequently, the combination of irinotecan and FU/LV has been approved as first-line chemotherapy for patients with metastatic colorectal cancer and constitutes the reference therapy against which other treatment options must be tested in the future. CONCLUSION: In this review, the clinical rationale and update of the present clinical status of irinotecan in the treatment of colorectal cancer and future prospects of irinotecan-based combinations are discussed.

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial

2014 ◽  
Vol 32 (23) ◽  
pp. 2423-2429 ◽  
Author(s):  
Helmut Oettle ◽  
Hanno Riess ◽  
Jens M. Stieler ◽  
Gerhard Heil ◽  
Ingo Schwaner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Karnofsky Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Gemcitabine Refractory

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

scholarly journals Advances and Controversies With Checkpoint Inhibitors in Bladder Cancer

2021 ◽  
Vol 15 ◽  
pp. 117955492110449
Author(s):  
Logan P Rhea ◽  
Jeanny B Aragon-Ching
Keyword(s):  
Bladder Cancer ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
First Line ◽  
Disease States ◽  
Metastatic Setting ◽  
Phase Iii Trials ◽  
Line Setting ◽  
Almost All ◽  
Confirmatory Phase

Immune checkpoint inhibitors have revolutionized the treatment of bladder urothelial cancers and have wide application in almost all disease states. Although several drugs have initially been shown to be beneficial in the second-line metastatic setting, there are still ongoing controversies and debate, including voluntary withdrawals of durvalumab and atezolizumab, along with the approval of agents in the first-line setting in the cisplatin-ineligible state based on inconsistent confirmatory phase III trials. As novel immunotherapy drugs are discovered and studied in various phases of clinical trials, these agents will continue to change the treatment landscape for bladder cancer patients. This review will discuss current available evidence and information and key pivotal trials using checkpoint inhibitors in bladder cancer.

scholarly journals Role of immunotherapy in the management of hepatocellular carcinoma: current standards and future directions

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
A. Weinmann ◽  
P.R. Galle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Statistical Significance ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Promising Therapeutic Approach

 The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (hcc) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (fda) and the European Medicines Agency. In phase ii studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval by the fda of nivolumab and pembrolizumab for second-line treatment. However, phase iii trials of nivolumab in the first line and pembrolizumab in the second line as single agents failed to reach statistical significance, although clinical benefit for a subset of patients with long durations of response could be demonstrated. Despite that setback, immunotherapy for hcc is a promising therapeutic approach, and the combination of immunotherapy with other treatment modal­ities such as monoclonal antibodies, tyrosine kinase inhibitors, or local therapies has the potential to increase the overall response rate and survival. Recently, the results of a phase iii trial of combination atezolizumab–bevacizumab compared with sorafenib showed a highly significant survival benefit and median overall survival that was not reached in the immunotherapy arm, making the combination the preferred standard of care in first-line therapy. Despite the impressive results and generally good toxicity profile of immunotherapy, patients who respond to therapy constitute only a subset of the overall population, and response rates are still limited. This review focuses on the currently reported results and ongoing clinical trials of checkpoint inhibitor–based immunotherapy in hcc.

A population-based study evaluating metastatic renal cell cancer (mRCC) patients treated with interferon (IFN) alone, first-line IFN then second-line sunitinib, or sunitinib alone

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15572-15572 ◽  
Author(s):  
C. K. Kollmannsberger ◽  
D. Y. Heng ◽  
N. Murray ◽  
K. N. Chi
Keyword(s):  
Overall Survival ◽  
Standard Treatment ◽  
Population Based ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Group A ◽  
Group B ◽  
The Impact

15572 Background: Previously, immunotherapy agents such as IFN were the only treatments available for mRCC. Sunitinib has demonstrated prolonged progression free survival in a phase III trial but overall survival benefit has yet to be determined and few patients (pts) with poor MSKCC prognostic profiles were included. Methods: The province-wide BC Cancer Agency Registry was cross-referenced to the central pharmacy database to identify all pts with the diagnosis of mRCC who were treated with IFN and/or sunitinib. Sunitinib became available after October 2005 under an expanded access program or as standard treatment. Three groups of pts were identified: Group A consisted of pts who received IFN alone between January 2003 to October 2005, Group B was all pts who progressed on first-line IFN after October 2005 and subsequently were treated with second-line sunitinib and Group C was all pts treated with first-line sunitinib. Baseline characteristics and overall survival were collected on all patients. Results: A total of 75 patients were identified with 36 patients in Group A, 23 patients in Group B, and 16 patients in Group C. Data are reported from the initiation of IFN in Group A and the initiation of sunitinib in Groups B and C. Median follow-up was 6.0 months in group A, 7.6 months in group B, and 6.2 months in group C. Median age of treatment initiation (62y vs. 60y vs. 62y), number of metastatic sites (>1 site in 63% vs. 61% vs. 56%), and Karnofsky performance status (79 vs. 86 vs. 81) were similar between groups A, B and C, respectively. The MSKCC prognostic profiles were favorable, intermediate and poor in 26%, 51% and 23% in group A, 17%, 65% and 17% in group B and 31%, 38% and 31% in group C, respectively. The estimated 6-month overall survival in groups A, B and C was 56%, 72% and 100%, respectively (log rank A vs C p=0.009; log rank B vs C p=0.042). Conclusion: With the limitations of retrospective analysis and preliminary follow-up, the introduction of sunitinib as standard treatment into the general population of patients with mRCC appears to be associated with a longer overall survival compared to patients treated with IFN alone. Population-based analysis on the impact of the introduction of sunitinib therapy is ongoing. No significant financial relationships to disclose.

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