Current Opinion in Oncology最新文献

Purpose of review: This review aims to provide an overview of recent advances in immunotherapy for small cell lung cancer (SCLC), with a focus on the current status of immune checkpoint inhibitors (ICIs), novel combination strategies, and key biomarkers.

Recent findings: The integration of ICIs into standard chemotherapy has established them as the first-line treatment for extensive-stage SCLC (ES-SCLC). The ADRIATIC trial further demonstrated the efficacy of ICI maintenance therapy in limited-stage SCLC. Additionally, combining radiotherapy with ICIs has shown promising synergistic effects, including the abscopal and radscopal effects. Ongoing investigations into the combination of ICIs with targeted therapies, such as antiangiogenic agents and DNA damage response inhibitors, have yielded encouraging preliminary results. Notably, the novel therapeutic agent tarlatamab, the first bispecific DLL3-directed CD3 T-cell engager, has recently received FDA approval for second-line treatment of ES-SCLC. Advances in omics technologies have shed light on the intra-tumor and inter-tumor heterogeneity of SCLC, leading to the identification of new molecular subtypes and biomarkers, thereby paving the way for precision medicine.

Summary: Despite the improved outcomes associated with immunotherapy in SCLC, the overall clinical benefit remains modest. Further preclinical and clinical studies are essential to identify optimal treatment regimens and enhance therapeutic efficacy.

Purpose of review: This review evaluates by analyzing recent studies whether pathological complete response (pCR) can be used as a reliable surrogate marker for overall survival (OS) in melanoma treated with neoadjuvant immunotherapy.

Recent findings: Trials like Neo-Combi, Neo-Trio and COMBI-Neo show that pCR is crucial for long-term success in targeted therapy for melanoma, while studies like OpACIN-neo and SWOG S1801 demonstrate that immunotherapy can provide durable benefits even with partial responses. Findings from NADINA and the INMC analysis highlight that immunotherapy achieves higher pathologic response rates and improved survival outcomes, offering broader benefits compared to the pCR-dependent outcomes of targeted therapy.

Summary: pCR serves as a critical prognostic biomarker across cancer types, with strong validation in breast cancer where it predicts long-term survival, particularly in aggressive subtypes like triple-negative and HER2-positive breast cancer. In melanoma, pCR is gaining prominence as a surrogate marker in neoadjuvant therapies, with its predictive value varying between targeted treatments - where achieving pCR is essential - and immunotherapies, which provide durable survival benefits even with partial responses. Despite its potential, the role of pCR as a universally reliable surrogate endpoint in melanoma requires further validation through cancer-specific studies to ensure accurate treatment guidance and personalized care.

Purpose of review: Squamous cell carcinoma (SCC) is the second most common skin cancer, with an increasing incidence. This review highlights this past year's advances regarding the understanding of its pathogenesis, newly introduced diagnostic methods and updates in prevention and treatment.

Recent findings: While the pathogenesis of SCC progression remains unclear, new sequencing techniques are helping to better characterize these tumours at the molecular level. Recently introduced noninvasive imaging techniques are rapidly transforming SCC diagnosis and follow-up. Although nicotinamide has not demonstrated significant benefit in reducing SCC incidence among transplant recipients, larger studies are needed to achieve statistical power. Tirbanibulin, a new field treatment for actinic keratosis is now available and well tolerated for use in areas up to 100 cm2. Surgery remains the cornerstone of SCC treatment and can now be complemented with cemiplimab, when advanced.

Summary: Recent years have seen a diagnostic revolution in dermatology, driven by noninvasive imaging and artificial intelligence; however, the physiopathogenesis of SCC progression remains poorly understood. In treatment, immune checkpoint inhibitors have shown good survival outcomes for advanced SCC. Research continues in the neoadjuvant setting and among transplanted patients, with encouraging preliminary results.

Purpose of review: Long-term immune related adverse events (irAEs) are an increasing reality in cancer patients treated with immune checkpoint inhibitors (ICIs) but remain under-reported. With the number of ICI treated patients increasing, we here aimed to expose the current evidence on their clinical presentations and diagnosis criteria.

Recent findings: First described in ICI validation trials, long term irAEs were further characterized through retrospective studies, providing clues on their frequency, clinical spectrum, risk factors and impact on patient's quality of life. Recent recommendations proposed consensual definitions to delineate their different subtypes, from delayed/late-onset irAE to chronic active and inactive irAE, paving the way to future prospective studies.

Summary: Knowledge of the different long-term irAE subtypes risk and clinical presentation is required to increase their detection and diagnosis, to better weight therapeutic decisions and to improve cancer patient's care.

Purpose of review: Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis, whereas its metastatic capacity carries a predilection for the brain. Although prophylactic cranial irradiation (PCI) has been used to address this problem, upcoming alternatives might necessitate reflection of its application in SCLC treatment.

Recent findings: The addition of immunotherapy to treatment guidelines has provided a new strategy for the management of brain metastases. Complementation of immunotherapy with active MRI surveillance could potentially replace PCI and avoid irradiation-related cognitive side effects. SCLC's molecular profile is heterogeneous, with differential response to treatment modalities between subgroups. Investigation of these variances might be essential to improve therapeutic outcomes in SCLC patients.

Summary: The role of PCI in SCLC treatment must be examined in light of immunotherapy. We summarize recent results, bearing SCLC subtypes and therapeutic vulnerabilities in mind, to derive tailored treatment strategies for SCLC patients in future settings.

Purpose of review: Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy.

Recent findings: Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes.

Summary: Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.

Purpose of review: In the evolving landscape of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) management, liquid biopsy offers unprecedented opportunities for guiding clinical decisions. Here, we review the most recent findings on liquid biopsy applications in HER2-positive BC and its potential role in addressing challenges specific to this BC subtype.

Recent findings: Recent studies have highlighted the significance of liquid biopsy analytes, primarily circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), in stratifying patients' prognosis, predicting treatment response, and monitoring tumor evolution in both early and advanced stages of BC. Liquid biopsy holds promise in studying minimal residual disease to detect and potentially treat disease recurrence before it manifests clinically. Additionally, liquid biopsy may have significant implication in the management of brain metastasis, a major challenge in HER2-positive BC, and could redefine parameters for determining HER2 positivity. Combining ctDNA and CTCs is crucial for a comprehensive understanding of HER2-positive tumors, as they provide complementary insights.

Summary: Research efforts are needed to address analytical challenges, validate, and broaden the application of liquid biopsy in HER2-positive BC. This effort will ultimately facilitate its integration into clinical practice, optimizing the care of patients with HER2-positive tumors.

Purpose of review: There is a critical need for timely and accurate decisions in breast cancer management. This narrative review aims to clarify the potential role of novel PET tracers in optimizing treatment strategies for different breast cancer subtypes.

Recent findings: 2-deoxy-2-[18F]-fluoro-D-glucose PET/computed tomography (FDG PET/CT) has a pivotal role in response assessment in metastatic breast cancer, despite its limitations in certain histological and molecular subtypes. Further PET radiopharmaceuticals have been proposed to address these clinical needing.

Summary: FES PET/CT demonstrates its usefulness in assessing ER expression and predicting response to therapy in luminal breast cancer, with implications for treatment optimization and monitoring. In HER2-positive and HER2-low breast cancer, HER2-targeted PET tracers show potential in assessing HER2 status, while their accuracy in predicting response to targeted therapies is still debated. PARP-targeted PET imaging holds potential for selecting patients for PARP inhibitors treatments, particularly in triple-negative breast cancer (TNBC), where imaging tools are crucial due to the absence of specific targets. Immunotherapy and antibody-drug conjugates (ADCs) are emerging treatment options for TNBC, and PET imaging targeting immune checkpoints could aid in treatment selection and response monitoring. The dynamic role of PET/CT imaging in tailoring breast cancer treatments requires further multidisciplinary research to validate the clinical utility of targeted tracers.

Purpose of review: Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer.

Recent findings: Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors).

Summary: More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.