ABSTRACT
Prostate cancer (PC) is generally a hormone-dependent tumor. Androgen deprivation therapy ( has been the standard of care in metastatic disease for more than 80 years. Subsequent studies have highlighted the efficacy of ADT even in earlier disease settings such as in localized disease or in the case of biochemical recurrence (BCR). Improved knowledge of PC biology and ADT resistance mechanisms have led to the development of novel generation androgen receptor pathway inhibitors (ARPI). Initially used only in patients who became resistant to ADT, ARPI have subsequently shown to be effective when used in patients with metastatic hormone-naive disease and in recent years their effectiveness has also been evaluated in localized disease and in case of BCR. The objective of this review is to describe the current role of agents interfering with the androgen receptor in different stages of PC and to point out future perspectives.
ABSTRACT
CONTEXT: Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC. OBJECTIVE: To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments. EVIDENCE ACQUISITION: A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC. EVIDENCE SYNTHESIS: From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel. CONCLUSIONS: Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients. PATIENT SUMMARY: Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.
ABSTRACT
Cisplatin remains a valid option in muscle-invasive or metastatic urothelial carcinoma, and is even more efficient when nivolumab is added. The well-known side-effect profile and the limited number of treatment cycles represent great advantages over modern drug combinations such as enfortumab-vedotin plus pembrolizumab.
Subject(s)
Cisplatin , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Humans , Cisplatin/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nivolumab/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Neoplasm StagingABSTRACT
BACKGROUND: In 2019, the breakthrough of the coronavirus 2 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represented one of the major issues of our recent history. Different drugs have been tested to rapidly find effective anti-viral treatments and, among these, antiandrogens have been suggested to play a role in mediating SARS-CoV-2 infection. Considering the high heterogeneity of studies on this topic, we decided to review the current literature. METHODS: We performed a systematic review according to PRISMA guidelines. A search strategy was conducted on PUBMED and Medline. Only original articles published from March 2020 to 31 August 2023 investigating the possible protective role of antiandrogens were included. In vitro or preclinical studies and reports not in the English language were excluded. The main objective was to investigate how antiandrogens may interfere with COVID-19 outcomes. RESULTS: Among 1755 records, we selected 31 studies, the majority of which consisted of retrospective clinical data collections and of randomized clinical trials during the first and second wave of the COVID-19 pandemic. CONCLUSIONS: In conclusion, we can state that antiandrogens do not seem to protect individuals from SARS-CoV-2 infection and COVID-19 severity and, thus, their use should not be encouraged in this field.
ABSTRACT
BACKGROUND: Darolutamide is an androgen receptor pathway inhibitor (ARPI) used in patients with prostate cancer (PC). In pivotal trials, it has demonstrated a favorable toxicity profile. There are no head-to-head comparison studies between the different ARPIs, but the efficacy of these drugs seems to be similar making the toxicity profile a key element for treatment selection. METHODS: We conducted a systematic review of all clinical trials assessing treatment with darolutamide for patients with PC using placebo as the control using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the safety of darolutamide versus placebo evaluating adverse events (AE) leading to treatment discontinuation and the rate of the AE reported as "AE of interest" in the ARAMIS trial. The comparison among darolutamide and the placebo group in terms of safety and tolerability was performed using odds ratio (OR) as meta-analytic outcome. RESULTS: We identified three articles comprising 2902 patients for the systematic review and meta-analysis (1652 treated with darolutamide and 1250 with placebo). Darolutamide did not increase AE leading to treatment discontinuation compared to placebo (pooled OR: 1.176, 95% CI 0.918-1.507, p = 0.633). Regarding the "AE of interest" there was no difference between darolutamide and placebo in terms of asthenia, cardiac arrhythmia, cardiac disorder, coronary artery disorder, depression mood disorder, falls, fatigue, heart failure, hot flushes, hypertension, mental-impairment disorder, rash, seizure and weight loss. The only "AE of interest" with a statistically significant difference in favor of placebo was bone fractures (pooled OR: 1.523, 95% CI 1.081-2.146). CONCLUSIONS: In our systematic review and meta-analysis, darolutamide showed a toxicity profile comparable to placebo with the exception of bone fractures. In the absence of head-to-head comparison studies between the different ARPIs, the results of our research suggest a preferred use of darolutamide in the approved settings.
Subject(s)
Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Androgen Receptor Antagonists/therapeutic use , Androgen Receptor Antagonists/adverse effectsABSTRACT
Inflammation is a hallmark of cancer1. In patients with cancer, peripheral blood myeloid expansion, indicated by a high neutrophil-to-lymphocyte ratio, associates with shorter survival and treatment resistance across malignancies and therapeutic modalities2-5. Whether myeloid inflammation drives progression of prostate cancer in humans remain unclear. Here we show that inhibition of myeloid chemotaxis can reduce tumour-elicited myeloid inflammation and reverse therapy resistance in a subset of patients with metastatic castration-resistant prostate cancer (CRPC). We show that a higher blood neutrophil-to-lymphocyte ratio reflects tumour myeloid infiltration and tumour expression of senescence-associated mRNA species, including those that encode myeloid-chemoattracting CXCR2 ligands. To determine whether myeloid cells fuel resistance to androgen receptor signalling inhibitors, and whether inhibiting CXCR2 to block myeloid chemotaxis reverses this, we conducted an investigator-initiated, proof-of-concept clinical trial of a CXCR2 inhibitor (AZD5069) plus enzalutamide in patients with metastatic CRPC that is resistant to androgen receptor signalling inhibitors. This combination was well tolerated without dose-limiting toxicity and it decreased circulating neutrophil levels, reduced intratumour CD11b+HLA-DRloCD15+CD14- myeloid cell infiltration and imparted durable clinical benefit with biochemical and radiological responses in a subset of patients with metastatic CRPC. This study provides clinical evidence that senescence-associated myeloid inflammation can fuel metastatic CRPC progression and resistance to androgen receptor blockade. Targeting myeloid chemotaxis merits broader evaluation in other cancers.
Subject(s)
Androgen Receptor Antagonists , Antineoplastic Agents , Chemotaxis , Drug Resistance, Neoplasm , Myeloid Cells , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Chemotaxis/drug effects , Disease Progression , Inflammation/drug therapy , Inflammation/pathology , Lewis X Antigen/metabolism , Myeloid Cells/drug effects , Myeloid Cells/pathology , Neoplasm Metastasis , Prostate/drug effects , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/metabolism , Androgen Receptor Antagonists/pharmacology , Androgen Receptor Antagonists/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.
ABSTRACT
OBJECTIVE: This study assessed the cost-effectiveness of nivolumab plus ipilimumab versus both sunitinib and pazopanib for the treatment of first-line unresectable advanced renal cell carcinoma (aRCC) from a healthcare system perspective in Switzerland. METHODS: A three-state partitioned survival model, consisting of progression-free, progressed disease, and death, was constructed. Efficacy estimates were based on data from the CheckMate 214 trial (NCT02231749) with a minimum follow-up of 42 months. Two Swiss oncologists were consulted to determine disease management resource use. Costs were derived from the Swiss tariff lists for outpatient (TARMED Online Browser 1.09) and inpatient (2020 data from Swiss diagnosis-related groups) treatments. Drug acquisition costs (ex-factory prices) were obtained from the March 2020 price list published by the Swiss Federal Office of Public Health. Treatment-specific EQ-5D-3L-based utilities were derived from CheckMate 214 using a French value set as a proxy for Switzerland. The model utilized a 1-week cycle length and a 40-year time horizon, with costs and effects discounted by 3.0% per annum. One-way sensitivity analyses, probabilistic analysis, and scenario analyses assessed the robustness of the results. RESULTS: Nivolumab plus ipilimumab yielded incremental 1.43 life-years and 1.36 lifetime discounted quality-adjusted life-years (QALYs) relative to sunitinib and pazopanib at an additional cost of 147,453 Swiss Francs (CHF) and CHF145,643, respectively. With an incremental cost-utility ratio of CHF108,326 per QALY gained versus sunitinib, and CHF106,996 per QALY gained versus pazopanib, the nivolumab plus ipilimumab combination can be considered a cost-effective option for the treatment of patients with aRCC in Switzerland, with a willingness-to-pay threshold of CHF200,000. Sensitivity and scenario analyses confirmed the robustness of the deterministic results. CONCLUSIONS: This study showed that nivolumab plus ipilimumab, which represents one of the standard-of-care first-line treatments for intermediate- or poor-risk aRCC patients, is a life-extending and cost-effective treatment option for patients in Switzerland.
ABSTRACT
Androgen receptor pathway inhibitors (ARPI) and polyadenosine diphosphate-ribose inhibitors (PARPi) are part of the standard of care in patients with metastatic castration-resistant prostate cancer (mCRPC). There is biological evidence that the association of ARPI and PARPi could have a synergistic effect; therefore, several ongoing clinical trials are investigating the efficacy of this combination with preliminary results that are not perfectly concordant in identifying patients who can obtain the most benefit from this therapeutic option. The purpose of this review is to describe the PARPi mechanisms of action and to analyze the biological mechanisms behind the interplay between the androgen receptor and the PARPi system to better understand the rationale of the ARPI + PARPi combinations. Furthermore, we will summarize the preliminary results of the ongoing studies on these combinations, trying to understand in which patients to apply. Finally, we will discuss the clinical implications of this combination and its possible future perspectives.
Subject(s)
Adenosine , Polymers , Prostatic Neoplasms , Receptors, Androgen , Male , Humans , Receptors, Androgen/genetics , Synthetic Lethal Mutations , Diphosphates , Ribose , Prostatic Neoplasms/drug therapy , Androgen Receptor AntagonistsABSTRACT
Metastatic castration resistant prostate cancer (CRPC) is an inevitably fatal disease. However, in recent years, several treatments have been shown to improve the outcome of CRPC patients both in the non-metastatic (nmCRPC) as well as the metastatic setting (mCRPC). In nmCRPC patients with a PSA doubling time <10 months, the addition of enzalutamide, apalutamide and darolutamide to androgen deprivation therapy (ADT) compared to ADT alone resulted in improved metastases free (MFS) and overall survival (OS). For mCRPC patients, several treatment options have been shown to be effective: two taxane based chemotherapies (docetaxel and cabazitaxel), two androgen-receptor pathway inhibitors (ARPI) (abiraterone and enzalutamide), two radiopharmaceutical agents (radium 223 and 177Lutetium-PSMA-617), one immunotherapy treatment (sipuleucel-T) and two poly ADP-ribose polymerase (PARP) inhibitors (olaparib and rucaparib). Pembrolizumab is US Food and Drug Administration (FDA) approved in all MSI high solid tumors, although a very small proportion of prostate cancer patients harboring this characteristic will benefit. Despite having a broad variety of treatments available, there are still several unmet clinical needs for CRPC. The objective of this review was to describe the therapeutic landscape in CRPC patients, to identify criteria for selecting patients for specific treatments currently available, and to address the current challenges in this setting.
ABSTRACT
Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments.
ABSTRACT
Objective: In this review, we summarize the current state of the art of primary mediastinal germ cell tumours (PMGCTs) and we highlight challenges and future research directions for this disease. Background: PMGCTs account for 1-3% of all germ cell malignancies and for 15% of adult anterior mediastinal cancers. In 60-70% of cases PMGCTs are represented by nonseminomatous germ cell tumours (GCTs), and in 30-40% of cases by seminomas. Even if PMGCTs share histological and biochemical characteristics with gonadal GCTs, they have peculiar clinical and biological features. Nonseminomatous PMGCTs have a poor prognosis, with a 5-year overall survival (OS) rate of 40-50% after platinum-based chemotherapy and surgery, and a long-term OS of only 10% after salvage treatment. Due to the rarity of this disease, no level 1 evidence is available from randomised trials for PMGCTs. The combination of bleomycin, etoposide, and cisplatin (BEP) or etoposide, ifosfamide and cisplatin (VIP) for 4 cycles are recommended as first line treatment options for nonseminomatous PMGCTs. Surgery of the residual disease after chemotherapy is fundamental in the treatment of nonseminomatous PMGCTs. PMGCTs have high TP53 pathway gene alterations, while targetable gene alterations are rarely identified, thus challenging the advance of precision medicine in this field. Methods: We performed a narrative review of international literature published in English on PMGCTs, focusing the attention on clinical trials, international guidelines and translational studies. Conclusions: Treatment of patients with PMGCTs is challenging and should be performed in experienced centers. International collaborations should become a priority to ensure optimal patient management. Clinical investigation of new therapeutic options remains an important unmet clinical need, and inclusion of patients in clinical trials should be encouraged. Liquid biopsy is a new promising strategy in PMGCTs.
ABSTRACT
In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.
ABSTRACT
BACKGROUND: Innovations in treatments, imaging and molecular characterisation have improved outcomes for people with advanced prostate cancer; however, many aspects of clinical management are devoid of high-level evidence. At the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, many of these topics were addressed, and consensus was not always reached. The results from clinical trials will most reliably plus the gaps. METHODS: An invited panel of 57 experts voted on 123 multiple-choice questions on clinical management at APCCC 2019. No consensus was reached on 88 (71.5%) questions defined as <75% of panellists voting for the same answer option. We reviewed clinicaltrials.gov to identify relevant ongoing phase III trials in these areas of non-consensus. RESULTS: A number of ongoing phase III trials were identified that are relevant to these non-consensus issues. However, many non-consensus issues appear not to be addressed by current clinical trials. Of note, no phase III but only phase II trials were identified, investigating side effects of hormonal treatments and their management. CONCLUSIONS: Lack of consensus almost invariably indicates gaps in existing evidence. The high percentage of questions lacking consensus at APCCC 2019 highlights the complexity of advanced prostate cancer care and the need for robust, clinically relevant trials that can fill current gaps with high-level evidence. Our review of these areas of non-consensus and ongoing trials provides a useful summary, indicating areas in which future consensus may soon be reached. This review may facilitate academic investigators to identify and prioritise topics for future research.
Subject(s)
Prostatic Neoplasms/epidemiology , Biomedical Research , Consensus , History, 21st Century , Humans , MaleABSTRACT
The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy, which to date remains the milestone for GCTs treatment. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. In the following report we explore the complex role of TP53 in GCTs cisplatin-sensitivity and resistance mechanisms, passing through several recent genomic studies, as well as its role in GCT patients with SCs, going through our experience of Center of reference for both GCTs and cancer predisposing syndromes.
Subject(s)
Genes, p53 , Neoplasms, Germ Cell and Embryonal/metabolism , Tumor Suppressor Protein p53/metabolism , Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Drug Resistance, Neoplasm , Humans , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/secondary , Tumor Suppressor Protein p53/geneticsABSTRACT
Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.
ABSTRACT
BACKGROUND: Ramucirumab is a VEGFR-2 antibody that has proven to prolong overall survival (OS) in patients with pretreated metastatic gastric/gastrooesophageal junction (GEJ) adenocarcinoma. We present data from patients treated with ramucirumab and paclitaxel or FOLFIRI after failure of at least one platinum- and 5-FU-containing chemotherapy (CHT) regimen. METHODS: In this retrospective two-center study, 56 patients with metastatic gastric cancer (47%) or adenocarcinoma of the GEJ (53%) were treated with paclitaxel and ramucirumab (n=38) as second-line (75%) or beyond second-line (25%) therapy. FOLFIRI-ramucirumab (FOLFIRI-R) (n=16) was given to patients with a short interval between taxane-based perioperative CHT and occurrence of metastatic disease or to those ineligible for paclitaxel. RESULTS: The median progression-free survival (PFS) and OS for patients treated with paclitaxel-ramucirumab (pacl-R) were 2.9 (95% CI: 2.3-3.6) and 4.4 (4.1-4.7) months, respectively, and those for patients treated with FOLFIRI-R were 5.9 (95% CI: 0.35-11.4) and 8.3 (6.6-10) months, respectively (P=0.05). We observed a trend towards prolonged PFS after perioperative taxane-based FLOT CHT (n=12) with FOLFIRI-R compared with pacl-R. Adverse events were manageable, with neutropenia and polyneuropathy (PNP) being the most common events. More than two treatment lines were given to 48.2% of patients. CONCLUSIONS: The use of ramucirumab in combination with FOLFIRI showed favourable PFS and OS in patients with prior treatments with platinum and/or taxane-based agents and allows further treatment lines after progression. In patients with taxane pretreatment or persistent high-grade PNP, the combination of FOLFIRI-R might be a promising combination.
ABSTRACT
Despite recent advances in the treatment of gastric cancer, mortality related to this disease is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Targeted treatments that include anti-angiogenic agents and the advent of immunotherapies can contribute to improved patient prognosis. Herein, we present an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and lower gastroesophageal junction, including those with human epidermal growth factor receptor 2 (HER2)-positive disease. The consensus considers the curative setting, as well as first-line to late-line systemic treatment options in the palliative setting. For HER2-positive disease, first-line and second-line therapies are discussed, as well as HER2 testing. Potential future therapies are also listed, with a focus on anti-angiogenic treatments and checkpoint inhibition, that might provide a further step forward in the management of patients with gastric cancer.