Current Treatment Options in Oncology最新文献

Opinion statement: Gastrointestinal stromal tumors (GIST) are the most common gastrointestinal soft tissue sarcomas, with an incidence of about 15 cases per million person-years. Approximately 15% of GIST develop due to succinate dehydrogenase deficiency (SDH-Def), and such tumors do not respond well to the tyrosine kinase inhibitors (TKIs) used to treat other GIST. Due to its indolent nature SDH-Def GIST can often be surveilled if asymptomatic. In our current practice we typically treat advanced symptomatic SDH-Def GIST with the anti-angiogenic TKIs, sequentially treating with sunitinib, regorafenib and pazopanib. This practice is based on limited data. This systematic review provides an update on new data (12/21/2021 to 9/26/2024) for systemic treatment of SDH-Def GIST, both with agents generally used to treat other GIST subtypes and with agents approved in other malignancies. Olverembatinib and rogaratinib have shown promising activity in pre-clinical models and small SDH-Def GIST cohorts. Other agents whose benefits are explored here include the immune checkpoint inhibitors (ICI) ipilimumab and nivolumab and temozolomide, whether as monotherapy or in combination with INBRX-109 (a pro-apoptotic antibody) or olaparib. Additional research into TKI agents with anti-vascular endothelial growth factor receptor (VEGFR) and anti-fibroblast growth factor receptor (FGFR) activity in this clinical setting is needed. Patients with SDH-Def will benefit more broadly from ongoing explorations of treatments with alternative mechanisms of action, especially those that exploit cellular pathways involved in SDH-Def GIST tumorigenesis.

Opinion statement: Recent clinical trials have investigated immune checkpoint inhibitors (ICIs) alone, in combination with tyrosine kinase inhibitors (TKIs), or with chemotherapy in angiosarcoma, yielding mixed results across subtypes. Single-agent ICI therapy, such as cemiplimab (ORR 27.8%), has shown responses primarily in UV- and radiation-associated angiosarcomas, likely due to their higher tumor mutation burden (TMB), while dual ICI therapy (SWOG S1609, ORR 25%) suggests potential benefit but remains limited in cutaneous disease. ICI-TKI combinations, such as cabozantinib plus nivolumab (Alliance A091902, second-line, ORR 59%), demonstrated significant efficacy in both cutaneous and non-cutaneous angiosarcomas, suggesting anti-angiogenic therapy may enhance ICI responses in tumors historically resistant to checkpoint blockade. ICI-chemotherapy combinations have been less consistent. The Alliance A091902 first-line trial (paclitaxel ± nivolumab) found no overall PFS benefit, though scalp/face angiosarcoma patients appeared to fare better, raising the question of whether ICI alone might be equally effective in this subset. The South Korean paclitaxel + avelumab trial (ORR 50%) showed promising response rates, but the lack of detailed subgroup analysis limits interpretation. Other chemotherapy-ICI combinations, such as doxorubicin plus pembrolizumab, have shown isolated responses but require further study in larger cohorts. Moving forward, better biomarkers are critical for identifying which patients benefit most from ICIs, and while TKI-ICI combinations appear to hold the most promise, chemotherapy-ICI strategies need further refinement to optimize sequencing and patient selection in angiosarcoma treatment.

Opinion statement: Gastric cancer (GC) is a deadly disease worldwide, and trastuzumab in combination with chemotherapy has been the standard first-line treatment for HER2-positive GC following the TOGA trial. Besides adjuvant therapy, HER2-directed therapy is widely used as neoadjuvant or translational therapy, and survival benefit even surgical opportunities is seen in these patients. However, resistance is not rare in recent years, and the second-line treatment for trastuzumab beyond progression has received widespread attention in GC. Moreover, current evidence cannot recommend trastuzumab for patients with IHC1+ HER2 low expression GC yet. Researchers are currently investigating whether GC patients with low HER2 expression could also benefit from HER2-directed therapies. In addition to using HER2 as a target for targeted therapy, HER2-mediated targeted delivery of cytotoxic drugs and targeted immunity have made important contributions to overcoming trastuzumab resistance in recent trials. HER2/neu-derived peptide epitopes vaccination and HER2-specific chimeric antigen receptor (CAR) therapy focus on reestablishing anti-tumor immunity in different ways and show significant anti-tumor activity. Other antibodies that target different regions of the HER2 receptor or block key downstream pathways such as AKT or PI3K also offer potential anti-tumor activity against HER2. HER2 use in GC will not be hampered by resistance or low expression and will play a bigger role. We review the current efforts to enable GC patients with trastuzumab-resistant and HER2 low-expressing accessible to HER2 targeted therapy and present our consideration for future HER2 in GC.

Opinion statement: Follicular lymphoma is the most prevalent form of indolent B-cell lymphoma, characterized by gradual disease progression and potential survival over several decades. Although the overall prognosis is typically favorable, some patients remain at risk for disease progression or transformation into a more aggressive variant. Recent advancements in the treatment of relapsed or refractory follicular lymphoma include cereblon modulators, kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and antibody-drug conjugates. Ongoing research into novel prognostic markers may improve the identification of patients at high risk for early progression, multiple relapses, or histological transformation, facilitating more precise and individualized treatment strategies.

Opinion statement: Multiple myeloma (MM) is classified as a lymphoproliferative disorder that remains an incurable malignancy despite improved patient survival with new drug therapies. Polymorphisms are essential in determining the effectiveness and outcome of treatments in MM. Despite significant advances, there needs to be more understanding of the underlying biological mechanisms that determine treatment outcomes. studies show that investigating gene polymorphisms involved in drug metabolism, DNA repair, inflammation, and apoptosis pathways can predict the effectiveness of treatment in MM patients. Therefore, these findings emphasize the potential of genetic profiling for predicting treatment outcomes and tailoring treatments to individual genetic profiles, which increases the efficiency and reduces the toxicity of MM treatments.

Opinion statement: Taxane-associated acute pain syndrome (T-APS) is one of the most common adverse effects of taxane treatment and significantly reduces the quality of life and activities of daily living of patients. T-APS is recognized as myalgia and arthralgia, which generally appear 1-3 days after taxane administration and last for approximately 7 days, at a wide range of sites. Recently, T-APS has been suggested to be not only an acute symptom but also a chronic symptom associated with chemotherapy-induced peripheral neuropathy (CIPN). The reported incidence of T-APS varies among studies, possibly owing to differences in observation points, evaluation methods, taxane administration methods, concomitant medications, or patient factors. Several factors, such as high taxane dose, paclitaxel use, metastatic setting, breast cancer, younger age, and co-administration of pegfilgrastim, are associated with symptom development. Several findings regarding T-APS management, such as prophylaxis using corticosteroids, Shakuyaku-Kanzo-to, and non-steroidal anti-inflammatory drugs (NSAIDs), are present. Corticosteroids for several days after taxane administration dose-dependently prevents and attenuates T-APS although we should be cautious about its longer administration. Prophylactic administration of Shakuyaku-Kanzo-to, a herbal compound, may be useful, although prescriptions are only available in limited areas. Etoricoxib, a selective cyclooxygenase-2 inhibiting NSAID, also reduces the incidence and severity of T-APS. Additionally, its prophylactic administration decreases CIPN. In contrast, evidence of symptomatic medication is limited. Taxanes are key chemotherapeutic agents used in the treatment of several types of cancer; therefore, further assessment of mechanisms of action and treatment of T-APS is necessary.

Opinion statement: There is an increasing use of medical management for gynecologic cancers given the rise in neoadjuvant therapies, delayed childbearing, and use of assisted reproductive technology. Chemotherapy, albeit broadly used in most gynecologic cancers, lacks long term data with respect to its associated gonadotoxicity and potential adverse pregnancy outcomes. Immunotherapy and other targeted therapies that have demonstrated promising responses in other tumor types are increasingly being studied in gynecologic malignancies. These therapies may offer opportunities for enhanced treatment response in an effort to minimize more toxic, invasive, or surgical management approaches that could have significant negative implications on fertility. Given that some of these therapies do not represent the standard of care and currently only exist in the experimental setting, detailed counseling and careful selection of patients for fertility sparing treatment remains critical. It is reasonable for patients with early stage, low-risk endometrial cancers to attempt conservative management while establishing clear treatment objectives. Early involvement of fertility specialists is necessary in order to optimize these patients' pregnancy goals. An emphasis on lifestyle changes and in particular weight loss should also be discussed with these patients. Neoadjuvant chemotherapy followed by fertility sparing surgery in cervix cancer patients with low-risk, small tumors shows promising results that suggest this can be a safe treatment option. Patients with advanced stage disease of any primary tumor or aggressive histology such as in many cases of ovarian cancer are not appropriate candidates for prioritization of fertility sparing treatment options. Ongoing and future studies will help to better identify appropriate patients and maximize medical management options in early-stage gynecologic cancers.

Opinion statement: Gynecological cancers, including cervical, endometrial, ovarian, and vulvovaginal cancer, have increasing incidence and mortality globally over the last three decades. In that time, there have been advances in medical therapies and paradigm shifts in surgical treatment which have resulted in a greater quality of life for patients. Clinicians have also refocused efforts to preventing gynecologic cancer. The state of screening and prevention is varied in each of the cancer types. The most comprehensive screening program and only preventable gynecological cancer is cervical cancer, which has been heavily studied since the 1900s. Cervical cytology, primary high-risk human papillomavirus (HPV) testing only, and co-testing are all effective in detecting cervical dysplasia and touted by the major medical. An additional arsenal is prevention through vaccination which has been shown to decrease cervical cancer. Unfortunately, the other gynecological cancers do not have effective screening strategies. The high rates of symptoms in endometrial cancer facilitate detection at an early stage but thus far, asymptomatic screening is only advocated in very high-risk population due to the invasive nature. Novel non-invasive mechanisms are currently under study though none have translated into clinical practice as of yet. Ovarian cancer remains the most innocuous with vague symptoms at onset resulting in late-stage diagnosis. Recommendations for prophylactic oophorectomy only apply to subsets of the population with predisposing genetic mutations. This has led to an ardent push for creative strategies such as opportunistic salpingectomy and a national genetic screening program. These efforts are in addition to the investigations underway researching radiologic, liquid biopsy, and genetic marker screening modalities for all gynecologic cancer. This review article discusses the state of screening, prevention, and recent advancements and pilot studies for each gynecological cancer.

Opinion statement: Symptoms of menopause and the sequelae of gynecologic cancer treatment can be severe in their physical and mental impact on patient quality of life. Survivors of certain gynecologic cancers - namely, early-stage, low-grade endometrial cancers; epithelial and germ cell ovarian cancers; and early-stage squamous cell cervical, vulvar, and vaginal cancers - as well as those who have undergone risk-reducing surgery for BRCA or Lynch syndrome mutations may safely use hormone replacement therapy (HRT). Treatment is ideally initiated in patients younger than age 60 or within ten years of menopause. The decision to start treatment should be made on an individualized basis after discussion of risks, benefits, and symptom severity with patients. Data suggest that the safest HRT regimens in this population include low-dose vaginal estrogen for the treatment of vulvovaginal symptoms, or low-dose systemic estrogen for the treatment of vasomotor symptoms, combined with progesterone in patients with an intact uterus. Therapies such as SSRIs/SNRIs, vaginal moisturizers, pelvic floor physical therapy, and psychosocial counseling should also be considered when appropriate for their effectiveness in managing menopausal symptoms without the potential risk of hormones.

Opinion statement: Colorectal cancer, ranking as the third most prevalent malignancy globally, substantially benefits from both immunotherapy and VEGF/VEGFR inhibitors. Nevertheless, the use of monotherapy proves inadequate in effectively tackling the heterogeneity of tumors and the intricacies of their microenvironment, frequently leading to drug resistance and immune evasion. This situation underscores the pressing need for innovative strategies aimed at augmenting the effectiveness and durability of treatments. Clinical research demonstrates that the combination of VEGF/VEGFR inhibitors (primarily including VEGF/VEGFR-targeted drugs and multi-kinase inhibitors) with immune checkpoint inhibitors creates a synergistic effect in the treatment of colorectal cancer. Our analysis explores how VEGF/VEGFR inhibitors recalibrate the tumor microenvironment, modulate immune cell functions, and influence the expression of immune checkpoints and cytokines. Furthermore, we critically evaluate the preclinical and clinical feasibility of these combined therapeutic approaches. Despite the potential for toxicity, the significant benefits and prospective applications of these strategies warrant thorough exploration. Exploring the synergistic mechanisms of these combined treatments has the potential to inaugurate a new paradigm in oncology, enabling more personalized and efficacious treatment modalities. Additionally, the synergy between VEGF/VEGFR inhibitors and nascent immunotherapies emerges as a promising field of inquiry.