Immunotherapy for gastric cancer: a 2021 update

Immunotherapy ◽  
2021 ◽  
Author(s):  
Christo Kole ◽  
Nikolaos Charalampakis ◽  
Sergios Tsakatikas ◽  
Nikolaos-Iasonas Kouris ◽  
George Papaxoinis ◽  
...  

Gastric cancer, the fifth most frequent cancer and the fourth leading cause of cancer deaths, accounts for a devastating death rate worldwide. Since the majority of patients with gastric cancer are diagnosed at advanced stages, they are not suitable for surgery and present with locally advanced or metastatic disease. Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types. This work presents a summary of the currently ongoing clinical trials and critically addresses the efficacy of a large spectrum of immunotherapy approaches in the general population for gastric cancer as well as in relation to tumor genetic profiling.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13071-e13071
Author(s):  
Evan Wenig ◽  
Reumu E. Birhiray

e13071 Background: Adenoid cystic carcinoma (ACC) accounts for less than 0.1% of all breast cancer cases. The disease typically remains localized and indolent, and frequently occurs with triple negative status. Methods: In patients with locally advanced or metastatic disease, chemotherapy for triple negative breast carcinoma is seldom effective. Thus new treatment paradigms are desired. Drug targeted analysis derived from next generation sequencing and identification of driver mutations may offer a bright future in treatment options in chemo-resistant malignancy. Results: A 53 year old woman presented with breast mass and mastectomy with stage pT3N0M0 triple negative ACC of the breast resulting in observation. She later relapsed with chest wall disease, resulting in resection and radiation therapy. Shortly thereafter, she relapsed with pulmonary metastatic disease. She was treated with carboplatin and doxorubicin which were discontinued due to disease progression. Liquid assay revealed an IDH2 mutation, prompting treatment with enasidenib with ongoing evidence of disease control at 4 months. Patient tolerated treatment well without grade 3 or 4 adverse reactions. A 48 year old woman presented with an increasing 9.5 cm unresectable breast mass without distant metastasis. Pathology showed triple negative ACC of the breast, resulting in chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with clinically progressive disease. She represented with necrotic and ulcerating changes of the breast. Foundational genomic testing showed an FGFR2 mutation. After four months of treatment with erdafitinib, she had resolution of pain and cessation of pain medication. Her therapy led to a grade 2 adverse event related to hyperphosphatemia. She underwent surgical resection with negative margins. Conclusions: These examples illustrate a potential treatment paradigm for a rare malignancy for which there is no standard of care. Here we present two desperate cases, one of which had a driver mutation of IDH2, and the other FGFR2 for which there are targeted therapies approved in other disease states. The use of these two agents resulted in clinical benefit. A patient with metastatic disease treated with enasidenib has ongoing disease control for over 4 months with minimal adverse reaction. A patient with advanced local disease requiring narcotics and gabapentin for pain control treated with erdafitinib had significant symptomatic control with successful cessation of pain medications and ability to undergo potentially curable mastectomy with negative margins despite progression on prior chemotherapy. In summary, ongoing research of ACC of the breast will be required. Alternative therapeutic options related to targeted treatment may offer promise to clinical outcomes in the future. For cases of locally advanced or metastatic disease, the use of targeted therapy may offer new therapeutic options.


2013 ◽  
Vol 50 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Candice Amorim de Araujo Lima SANTOS ◽  
Gustavo Fernandes Godoy ALMEIDA

Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.


2017 ◽  
Vol 41 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Seungyoon Nam ◽  
Jun-Won Chung ◽  
Jun-Young Yang

Background/Aims: Gastric cancer (GC), the third-leading cause of cancer death in the world, is typically diagnosed only in its advanced stages. WNT signaling has been associated with clinicopathological characteristics in diverse cancer types. But the systematic analysis of WNT5A, a member in the signaling, has not been inspected. Thus, our study used a meta-analysis to statistically associate WNT5A expression with GC clinicopathological characteristics. Methods: For a systematic literature review of GC in combination with the WNT signaling molecule WNT5A, we searched for PubMed, Cochrane Library, and Web of Science. It led to the five cohorts, in four eligible studies, consisting of 1,034 patients (617 WNT5A-positive and 417 WNT5A-negative patients). These patients were inspected by the library “meta” in R software for our meta-analysis. Results: Our meta-analysis, revealed a statistically significant associations of WNT5A-positivity with lymph node metastasis (p=0.0047), some types of Lauren diffuse subtype GCs (p<0.0001), advanced tumor depth (p<0.0001), and advanced UICC stages (p=0.0461) with no observation of bias or confounding factors. Conclusions: These results support the feasibility of targeting this embryonic signaling pathway, both for therapy, and as a biomarker to “guide” various individual interventions (i.e., “personalized medicine”).


2021 ◽  
pp. OP.20.00397
Author(s):  
Shaila J. Merchant ◽  
Weidong Kong ◽  
Bishal Gyawali ◽  
Timothy P. Hanna ◽  
Wiley Chung ◽  
...  

PURPOSE: Clinical trials have shown that palliative chemotherapy (PC) improves survival in patients with incurable esophageal and gastric cancer; however, outcomes achieved in routine practice are unknown. We describe treatment patterns and outcomes among patients treated in the general population of Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify patients with esophageal or gastric cancer from 2007 to 2016, and data were linked to other health administrative databases. Patients who received curative-intent surgery or radiotherapy were excluded. Factors associated with the receipt of PC were determined using logistic regression. First-line PC regimens were categorized, and trends over time were reported. Survival was determined using the Kaplan-Meier method. RESULTS: The cohort included 9,848 patients; 22% (2,207 of 9,848) received PC. Patients receiving PC were younger (mean age, 63 v 74 years; P < .0001) and more likely male (71% v 65%; P < .0001). Thirty-seven percent of non-PC patients saw a medical oncologist in consultation. Over the study period, utilization of PC increased (from 11% in 2007 to 19% in 2016; P < .0001), whereas the proportion of patients receiving triplet regimens decreased (65% in 2007 to 56% in 2016; P = .04). In the PC group, the median overall and cancer-specific survival from treatment initiation was 7.2 months. CONCLUSION: One fifth of patients with incurable esophageal and gastric cancer in the general population receive PC. Median survival of patients treated in routine practice is inferior to that in clinical trials. Only one third of patients not treated with PC had consultation with a medical oncologist. Further work is necessary to understand low utilization of PC and medical oncology consultation in this patient population.


2020 ◽  
pp. 107815522097102
Author(s):  
Kirollos S Hanna ◽  
Maren Campbell ◽  
Adam Kolling ◽  
Alex Husak ◽  
Sabrina Sturm ◽  
...  

Urothelial carcinoma is the sixth most common cancer type in the United States. Although most patients present with early stage disease which is associated with improved outcomes, many will progress to locally advanced or metastatic disease. Immune checkpoint inhibitors have significantly impacted the treatment paradigm for patients and have resulted in improved survival rates. Despite their proven efficacy, many ongoing clinical trials continue to refine combinations with chemotherapy, sequencing of therapies and the role of ligand expression. Additionally, novel targets have been identified for advanced urothelial carcinoma and have led to the approval of the antibody-drug conjugate, enfortumab vedotin, and the fibroblast growth factor receptor-targeted, erdafitinib. Enrollment in a clinical trial is strongly encouraged for all stages of advanced or metastatic disease. Numerous ongoing clinical trials are likely to impact the treatment armamentarium for patients. In this manuscript, we highlight key updates in the clinical management for patients and outline ongoing trials.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 21-21
Author(s):  
Jaejoon Han ◽  
Jin Won Kim ◽  
Se Hyun Kim ◽  
Jeong-Ok Lee ◽  
Yu Jung Kim ◽  
...  

21 Background: Participation in clinical trials gives patients with cancer a chance to receive potential benefits, such as experimental treatment, meticulous follow-up and toxicity managements. We aimed to assess the evidence that such an effect exists in patients with gastric cancer. Methods: Clinical characteristics and overall survival of patients with metastatic or recurrent gastric cancer who received fluoropyrimidine and platinum combination palliative chemotherapy within or outside clinical trials at tertiary referral hospital from January 2010 to December 2012 were retrospectively analyzed. Results: Of the 244 patients, 84 patients (34%) were enrolled in clinical trials. During the study period, 20 patients in four phase 3 trials, 54 patients in eight phase 2 trials and ten patients in two phase 1 trials were participated in clinical trials. Twenty patients (8%) at first-line and 64 patients (38%) at second-line or later were enrolled in clinical trials. Younger age (P = 0.014), metastatic disease (P = 0.015) and HER2 IHC status (P = 0.005) were correlated with participation in clinical trials. The median overall survival of patients who participated in clinical trials at first-line was better than those who did not participated in clinical trials, although it was not statistically significant (16 months and 11 months, respectively, P = 0.407). Number of participation in clinical trials was not associated with survival outcome (1 versus ≥ 2 trials: 15 months and 18 months, respectively, P = 0.545). Second-line chemotherapy was administered in 167 patients. The median overall survival of patients who participated in clinical trials at second-line or later was also better than those who did not participated in clinical trials, however, it was not statistically significant (9 months and 6 months, respectively, P = 0.101). Conclusions: Younger patients, metastatic disease, positive HER2 IHC status, and clinical setting of second-line or later were associated with more participation in clinical trials. The median overall survival was numerically longer in patients who were enrolled in the clinical trials although it was not statistically significant.


Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 14
Author(s):  
Nikolaos Mitsimponas ◽  
Georgios Zervopoulos

Bladder metastasis from gastric cancer is a unique clinical entity, which can be revealed infrequently in patients with metastatic gastric cancer. Secondary neoplasms to the bladder are also a less frequent clinical entity representing only 15% of all bladder neoplasms. Gastric cancers consist of an exceptionally small percentage of all secondary bladder neoplasms. Until now only 27 cases were recorded in the international medical literature. The current work analyzes a 65-year old male patient who presented initially with a locally advanced gastric adenocarcinoma. He was treated with a combination of total gastrectomy and perioperative chemotherapy. Eight months later presented a relapse with bladder metastasis, liver metastasis and peritoneal involvement. Furthermore, in this manuscript, we conducted a review of the recorded cases with bladder metastasis from gastric cancer. In the most of cases the diagnosis of bladder metastasis was metachronous with an average time of presentation in four years after the primary diagnosis of gastric cancer and most of the patients of our review presented with urinary symptoms at the time of diagnosis of bladder metastasis. Concerning the management of the metastatic disease surgical management with total or partial cystectomy was performed in 11% of patients and TUR was performed in 22% of patients. Palliative chemotherapy for the management of metastatic disease was initiated in 46% of patients.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5471
Author(s):  
Farzaneh Kordbacheh ◽  
Camile S. Farah

Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice.


2017 ◽  
Vol 5 (2) ◽  
pp. 5-11 ◽  
Author(s):  
Attila Kollár ◽  
Bernd Kasper

Soft tissue sarcomas are rare tumors of mesenchymal origin comprising about 1% of all adult malignant diseases. Systemic therapy for locally advanced and metastatic disease was restricted for decades to a few effective and approved agents, such as doxorubicin or ifosfamide. However, numerous clinical trials and new drug developments such as trabectedin, pazopanib, olaratumab or eribulin have recently enriched the therapeutic armamentarium in the treatment of patients with advanced soft tissue sarcomas and will be presented in the following review.


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