2767 Second line systemic treatment options for recurrent/advanced cervical cancer - The Royal Marsden experience

2015 ◽  
Vol 51 ◽  
pp. S553
Author(s):  
S. Boussios ◽  
D. Glaessgen ◽  
A. Okines ◽  
S. Lalondrelle ◽  
A. Taylor ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Advanced Cervical Cancer ◽  
Second Line

Molecular profiles and immune checkpoint inhibitor-related biomarkers analysis in advanced cervical cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18003-e18003
Author(s):  
Qin Xu ◽  
Chuanben Chen ◽  
Yang Sun ◽  
Yibin Lin ◽  
Jing Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Figo Stage ◽  
Advanced Cervical Cancer ◽  
Single Nucleotide Variants ◽  
Paired Samples ◽  
Target Capture ◽  
Pathological Subtype ◽  
Molecular Profiles

e18003 Background: Treatment options for advanced cervical cancer (ACC) are limited and patients experiencing recurrence after first-line chemotherapy and bevacizumab have a poor prognosis. Checkpoint inhibitors targeting the PD-1/PD-L1 are promising treatment option. However, related genomic biomarker study is rare reported in ACC. Methods: We prospectively enrolled 102 pts with ACC. Tumor and plasma samples were obtained to analysis genomic profiles. DNA was sequenced by target-capture deep sequencing with the pan-cancer panel. TMB of tissue (tTMB) and blood (bTMB) analysis interrogated single nucleotide variants, small insertion and deletion. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1. Results: The median age of enrolled pts was 63 yrs, and most (84.3 %, 86/102 pts) weresquamous carcinoma. A total of 93 tissues and 96 plasma were collected from 102 pts. The most frequently mutated genes were PIK3CA (40.9%, 38/93 pts), KMT2D (35.5%, 33/93 pts), and KMT2C (28.0%, 26/93 pts) in tissues. 80% (77/96 pts) of plasma was detected positive, with PIK3CA (23.4%, 18/77 pts), KMT2D (20.8%, 16/77 pts), KMT2C (20.8%, 17/77 pts) mutant frequently. Among 87 pts with paired samples, at least a tumor-derived mutation was detected in 35 (40.2%)plasma. Median of tTMB was 11.9 mut/Mb, and 45% pts were TMB-H. Significant correlation was found between tTMB and bTMB (Pearson r = 0.39, P = 0.001). Higher tTMB was identified in KMT2D- or KMT2C-mut pts (P = 0.002 or P = 0.01, respectively). tTMB showed no relation with clinic characteristics, including pathological subtype, FIGO stage, and status of distant metastasis. PD-L1 expression (CPS≥1) was identified in 53 pts (93 %, 53/57) and mutually independent with TMB status. Conclusions: Molecular profiles and TMB in plama showed high consistence with that in tissue. Prospective clinical trial is ongoing to determine the genomic biomarkers and the PD-L1 expression as predictive factors for the ICI efficacy in ACC (ChiCTR1900023015).

scholarly journals Management of a Patient with Metastatic Colorectal Cancer and Liver Metastases

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Muhammad Wasif Saif
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Cortical Blindness ◽  
Second Line ◽  
First Line ◽  
Current Case ◽  
Transient Cortical Blindness

Liver metastases are commonly encountered in patients presenting with metastatic colorectal cancer (mCRC); resection is the treatment of choice. A number of systemic treatment options are currently available for such patients, including the use of 5-fluorouracil-based chemotherapies and oxaliplatin (e.g., FOLFOX) in combination with biologic agents that target angiogenesis (e.g., bevacizumab). For patients with progression following first-line treatment, current second-line options include a change in chemotherapy with bevacizumab (for patients who did or did not receive prior bevacizumab) or FOLFIRI in combination with aflibercept, a more recently approved antiangiogenesis therapy. Neurotoxicity is a well-established adverse event of oxaliplatin-based therapy. The current case details an mCRC patient with liver metastases who was treated with a capecitabine and oxaliplatin regimen (XELOX), and experienced two episodes of transient cortical blindness possibly related to oxaliplatin. After disease progression, the patient was switched to a regimen of FOLFIRI and aflibercept and did well on this second-line regimen.

scholarly journals Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article

2021 ◽  
pp. 1-10
Author(s):  
Alexander R. Siebenhüner ◽  
Sara De Dosso ◽  
Daniel Helbling ◽  
Christoforos Astaras ◽  
Petr Szturz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Current Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Her 2 ◽  
The Impact

<b><i>Background:</i></b> Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. <b><i>Summary:</i></b> Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, <i>Epstein-Barr virus</i> expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and &#x3c;70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. <b><i>Key Message:</i></b> In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.

Overview of systemic treatment in recurrent and advanced cervical cancer: a primer for radiologists

2018 ◽  
Vol 44 (4) ◽  
pp. 1506-1519 ◽  
Author(s):  
Colin Marshall ◽  
Maharshi A. Rajdev ◽  
Bhanusupriya Somarouthu ◽  
Nikhil H. Ramaiya ◽  
Francesco Alessandrino
Keyword(s):  
Cervical Cancer ◽  
Systemic Treatment ◽  
Advanced Cervical Cancer

scholarly journals Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e001126
Author(s):  
Claire F Friedman ◽  
Alexandra Snyder Charen ◽  
Qin Zhou ◽  
Michael A Carducci ◽  
Alexandre Buckley De Meritens ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Primary Objective ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Recurrent Cervical Cancer ◽  
Platinum Based Chemotherapy

BackgroundThere are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.MethodsWe report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsIn the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.ConclusionsThe combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

scholarly journals Will the carboplatin-paclitaxel-bevacizumab combination become the preferred option as the first line in advanced cervical cancer? A small experience from a single oncologic Center

2017 ◽  
Vol 5 (1) ◽  
pp. 21-24
Author(s):  
Raquel Bratos Lorenzo ◽  
Luisa Sánchez Lorenzo ◽  
Antonio González-Martín
Keyword(s):  
Cervical Cancer ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Advanced Cervical Cancer ◽  
Recurrent Cervical Cancer ◽  
Curative Therapy ◽  
Screening Programs ◽  
Medical Need ◽  
Important Health ◽  
Future Therapy

Background: Despite the widespread introduction of screening programs, cervical cancer remains an important health problem, particularly in developing countries. Treatment options for patients with metastatic cancer and persistent or recurrent disease after curative therapy are limited and represent an unmet medical need. Patients and Methods: We report three clinical cases of metastatic cervical cancer in women treated with the combination of carboplatin, paclitaxel and bevacizumab. We also discuss current and future therapy for metastatic or recurrent cervical cancer, including ongoing investigations into the addition of bevacizumab to carboplatin/paclitaxel chemotherapy and the role of bevacizumab as maintenance therapy. Results and Conclusion: All three women received clinical benefit from the combination, including one complete and two partial responses. The tolerability of bevacizumab was excellent. Carboplatin/paclitaxel appears to be an acceptable and better tolerated alternative to cisplatin/paclitaxel in advanced or recurrent/persistent disease, and the carboplatin/paclitaxel/bevacizumab combination is under investigation for metastatic, recurrent or persistent cervical cancer in clinical trials such as the CECILIA trial (NCT02467907); the awaited results will add to the evidence for the use of this combination chemotherapy regimen in advanced cervical cancer.

scholarly journals Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1026
Author(s):  
Jana Wood ◽  
Sayeda Yasmin-Karim ◽  
Romy Mueller ◽  
Akila N. Viswanathan ◽  
Wilfred Ngwa
Keyword(s):  
Cervical Cancer ◽  
Tumor Regression ◽  
Treatment Options ◽  
Metastatic Tumor ◽  
Current Treatment ◽  
Immune Memory ◽  
Advanced Cervical Cancer ◽  
Term Survival ◽  
Fraction Dose ◽  
Radiotherapy Dose

Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (p = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.

A phase II trial of weekly one hour paclitaxel as second-line therapy for endometrial and cervical cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15013-15013
Author(s):  
H. D. Homesley ◽  
L. Vaccarello ◽  
G. Lowendowski ◽  
A. A. Elbendary
Keyword(s):  
Cervical Cancer ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Stable Disease ◽  
Weekly Paclitaxel ◽  
Advanced Cervical Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Measurable Disease

15013 Background: The antitumor activity of other regimens of paclitaxel (from Bristol-Myers Squibb Oncology, Bristol-Myers Squibb Company, Princeton, NJ, U. S. A.) has been identified in both cervical and endometrial cancer. A less toxic and better tolerated regimen for paclitaxel is a one hour infusion every 7 days. The primary aim of this study was to assess the activity of weekly paclitaxel in patients with recurrent or refractory endometrial cancer or squamous cell cancer of the cervix who had failed one prior chemotherapy regimen and had measurable disease. The nature and degree of toxicity of paclitaxel administered in this schedule in this group of patients was assessed. Methods: Eligible patients had initial histologic diagnosis. All patients presented with persistent or recurrent measurable disease with no more than one prior chemotherapeutic regimen and a GOG Performance Status of 2 or better. At entry hematologic and all other labs were within normal limits. Patients received paclitaxel 80 mg/m2 over one hour every 7 days. One cycle consisted of four weeks and patients had to receive at least two cycles of therapy to be evaluable for response unless progression occurred during the first eight weeks of the trial. Response by measurable disease change and survival were the endpoints of the trial. Results: Forty-three patients were registered. Evaluable for response were 15/16 patients with endometrial cancer and 20/29 patients with advanced cervical cancer. For the endometrial cancer patients 4 of 15 responded. Two of four responders had complete responses with durations of response of 16 to 23 weeks. Stable disease was present in 33%. There were two responders (one a complete response) in the 20 evaluable patients with cervical cancer while 35% had stable disease. Adverse effects were minimal and easily managed with dose adjustments as needed. Conclusions: In this trial, weekly paclitaxel as second line therapy had a response rate of 27% (4/15) in endometrial carcinoma but only 10% in advanced cervical cancer (2/20). Although confirmatory larger trials are needed, weekly paclitaxel appears promising for advanced endometrial carcinoma but not for squamous cell carcinoma of the cervix. [Table: see text]

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