Therapeutic Advances in Medical Oncology最新文献

Patients with luminal breast cancer (BC) may develop central nervous system metastases in 20%-40% of cases. Radiation or surgical therapy represents the cornerstone of treating central nervous system metastases. Meanwhile, the best practice for metastatic luminal BC involves using cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy. To our knowledge, this is the first case to report a dramatic response of breast metastases to abemaciclib plus endocrine therapy without radiation therapy, particularly in a patient who presented with seizures and sudden coma. She received brain surgery to control a large bleeding metastasis. Abemaciclib was crushed and diluted in water for administration via the nasogastric tube, while an upfront fulvestrant was given since aromatase inhibitors cannot be diluted. Beyond the radiological response, the clinical improvement was notable, with complete symptom recovery to the point where she is again working. Our paper supports the activity of abemaciclib in brain metastases from luminal BC and includes a review of the medical literature. Further investigation is warranted in this clinical setting.

Pancreatic cancer is a rising cause of cancer death. Therapeutic options are scarce and of limited efficacy. Up to 26% of patients with metastatic pancreatic cancer could benefit from targeted therapies. We report here for the first time the case of three patients with metastatic pancreatic ductal adenocarcinoma (PDAC) without KRAS alteration for whom an activating mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene was found through mainstreaming NGS. The EGFR variant was confirmed on multiple tumor samples and by circulating tumor DNA (ctDNA) analysis in two patients. The three patients were treated with osimertinib with early molecular, biologic, and morpho-metabolic responses. At the last follow-up, one patient had an ongoing response after 17 months, and disease control had been maintained for 8 and 6 months in the other two. Known resistance mechanisms were observed on ctDNA analysis at progression. These observations demonstrate the benefit of osimertinib for treating EGFR-mutated PDAC and highlight the interest in investigating rare molecular alterations, especially in patients without KRAS alterations.

Background: Currently, guidelines prohibit the addition of targeted drugs in neoadjuvant chemotherapy (NAC) for initially resectable colorectal liver metastasis (CRLM).

Objective: Nevertheless, efficacy data of NAC combined with bevacizumab (Bev) for initially resectable CRLM with risk factors for recurrence (RFR) are lacking.

Designs: We conducted a multicenter real-world cohort study to retrospectively analyze the efficacy and feasibility of NAC combined with Bev for CRLM with RFR.

Methods: The patients were divided into the NAC alone group and NAC combined with the Bev group. We designated progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) as the outcomes. Kaplan-Meier, Cox proportional hazards regression models, and subgroup analysis were utilized. RFR was a clinical risk score of 3-5. Subgroup analysis was applied to explore which subgroup was more suitable for NAC combined with Bev.

Results: Between 2015 and 2020, this multicenter real-world study encompassed 335 CRLM patients from six medical centers who underwent curative hepatectomy following NAC. Two hundred seventeen patients were in the NAC alone group, and 118 received NAC combined with Bev. The NAC alone group exhibited an ORR of 51.15%, compared to 66.95% in the NAC combined with Bev (p = 0.005). The R0 resection rates achieved 91.71% for the NAC alone group and 94.92% for the NAC combined with Bev (p = 0.276). Three-year PFS rate was 27.6% for NAC alone and 41.5% for the NAC combined with the Bev group (p = 0.006). Furthermore, the 3-year OS was calculated to be 57.0% for the NAC alone and 66.7% for the NAC combined with Bev patients (p = 0.079).

Conclusion: For initially resectable CRLM patients with RFR, NAC combined with Bev exhibited a higher ORR and longer PFS.

Chinese clinical trial registry: ChiCTR2400082966.

In recent years, several global phase III trials have shown that combinations of immune checkpoint inhibitors (ICIs) offer superior efficacy and survival compared to multi-kinase inhibitors, establishing them as the gold standard for treating patients with advanced hepatocellular carcinoma (HCC). This success has led to investigations into expanding the use of immunotherapy into various other settings and populations, including neoadjuvant and adjuvant therapies, patients with decompensated liver function and those awaiting liver transplantation. Despite its proven efficacy, a significant number of patients still develop resistance to immunotherapy, highlighting the need for innovative strategies to address this challenge. Approaches aimed at enhancing tumour immunogenicity, such as combining immunotherapy with transarterial chemoembolization or radiation therapies, show significant promise. Additionally, novel immunotherapeutics - such as triplet therapy, bispecific antibodies, adoptive T-cell therapy and cancer vaccines - are in early development for HCC. These agents have demonstrated potential for synergistic effects with existing ICIs, with initial studies yielding positive outcomes. In this review, we offer our future perspective on immunotherapy, emphasizing emerging indications, novel combination strategies and the development of new immunotherapeutic agents. Overall, the future of immunotherapy in HCC is brimming with extraordinary potential, set to transform the treatment landscape and redefine the possibilities for managing this challenging disease.

Antibody-drug conjugates (ADCs) offer a promising therapeutic approach for various cancers, enhancing the therapeutic window while mitigating systemic adverse effects on healthy tissues. ADCs have achieved remarkable clinical success, particularly in treating breast cancer, becoming a standard therapy across all subtypes, including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer. Although designed to selectively target antigens via monoclonal antibodies, ADCs can exhibit toxicity in normal tissues, often due to off-target effects of their cytotoxic payloads. Understanding and managing these toxicities according to established guidelines are crucial for enhancing ADC clinical efficacy, minimizing adverse events, and ultimately improving patient outcomes. This review comprehensively examines the toxicities of ADCs employed in breast cancer treatment and explores their management strategies. Furthermore, we investigate novel ADCs beyond trastuzumab deruxtecan and sacituzumab govitecan, evaluating their potential efficacy and corresponding safety profiles.

Background: Breast cancer screening in transgender women, particularly those undergoing hormone therapy, remains understudied. Limited screening guidelines exist for transgender individuals, creating a need for tailored recommendations. This study addresses breast cancer screening outcomes in Thai transgender women using mammography and ultrasound.

Objectives: To assess breast imaging characteristics and screening outcomes in transgender women in Thailand and identify factors associated with breast density.

Design: A descriptive correlation study with a cross-sectional design.

Methods: Sixty-six transgender women over 40 years of age, who had been on hormone replacement therapy for at least 5 years, were recruited from three clinics. Participants underwent mammography and breast ultrasound, with imaging analyzed using the Breast Imaging-Reporting and Data System (BI-RADS) system. Data were analyzed with descriptive statistics and Spearman's correlation.

Results: The average age of participants was 49.2 years, with an average of 16.3 years of hormone use. Of the participants, 80.3% had undergone breast augmentation. Most participants (86.4%) were classified as BI-RADS 2 and dense breast tissue. Screening findings were mostly negative or benign (94%), with the remaining 6% demonstrating probably benign findings. No signs of malignancy were detected. There was no significant correlation between age, BMI, hormone use duration, BI-RADS, and breast density.

Conclusion: Breast cancer screening among transgender women in Thailand showed high rates of dense breast tissue and low abnormality detection. Moreover, most of them have previously undergone breast augmentation. Therefore, screening guidelines should use both mammography and ultrasound for early detection.

The introduction of the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors abemaciclib and ribociclib to the adjuvant setting marks a significant advancement in the treatment of hormone-receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (HR+, HER2- EBC). Despite significant strides in early detection and treatment, many patients continue to face the risk of disease recurrence, highlighting the need for more effective adjuvant therapies. These CDK4/6 inhibitors, combined with adjuvant endocrine therapy, have shown promising efficacy in reducing recurrence rates while maintaining a manageable safety profile, as evidenced by the monarchE and NATALEE trials. This paper explores the integration of adjuvant CDK4/6 inhibitors into clinical practice, focusing on disease-free survival and safety outcomes. Key considerations in selecting between abemaciclib and ribociclib are discussed, including patient risk profiles, efficacy and safety profiles, treatment duration, and individual patient preferences. In addition, we discuss managing adverse events to prevent premature discontinuation, with strategies that include dose holds, dose reductions, proactive symptom management, and patient education. The paper also highlights strategies to enhance patient medication adherence and the involvement of multidisciplinary care teams to support treatment delivery. As research continues to evolve, additional follow-ups of the monarchE and NATALEE trials and future trials will further refine patient selection and treatment sequencing, ultimately improving outcomes and enhancing the quality of life for patients with HR+, HER2- EBC.

Background: Transarterial chemoembolization (TACE) is a potential conversion therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). However, therapeutic options following conversion therapy are still controversial.

Objectives: This study aimed to compare the efficacy and safety of surgical resection (SR) and microwave ablation (MWA) after TACE conversion therapy for uHCC.

Design: A retrospective, multi-institutional study.

Methods: From June 2008 to October 2022, 8842 consecutive uHCC patients underwent initial TACE at 15 hospitals were identified. Among them, 1348 eligible patients who received TACE conversion therapy were included. The propensity score matching (PSM) was applied to reduce selection bias. To explore the effect of age on conversion therapy, a therapeutic factor analysis with age change was performed. The overall survival (OS) and disease-free survival (DFS) were compared using the Kaplan-Meier method with the log-rank test.

Results: After PSM 1:1, 542 patients in the MWA group were matched with those in the SR group. SR demonstrated better long-term survival outcomes (median OS, 10.6 vs 5.8 years, HR:1.83, 95% CI: 1.48-2.25, p < 0.001 and median DFS, 3.2 vs 2.5 years, HR: 1.27, 95% CI:1.09-1.49, p = 0.003) than MWA. There was an improvement in the 5-year DFS rate for MWA from 17.1% during 2009-2016 to 37.3% during 2017-2022, becoming comparable to the 40.8% of SR (p = 0.129). When the uHCC patients downstage met Milan criteria, the long-term OS and DFS were comparable between two groups (both, p > 0.05). SR presents an OS advantage over MWA at the age (years) of 45-54 (p = 0.036), 55-65 (p = 0.001), and >65 (p < 0.001), except <45(p = 0.140).

Conclusion: MWA might be acceptable as an alternative to SR in first-line therapeutic scheme after TACE conversion therapy for uHCC, especially, for the aged <45 years cohorts.

[This corrects the article DOI: 10.1177/17588359241307199.].

Small-cell lung cancer (SCLC) is a highly aggressive and rapidly proliferative malignancy that has historically had limited therapeutic advancements. Recent advancements in the understanding of SCLC have led to attempts at subtyping the disease based on transcription factor characteristics, offering new insights into its biology and potential therapeutic targets. In addition, significant progress has been made in developing treatment regimens, providing new hope for improved patient outcomes. The introduction of immune checkpoint inhibitors, such as atezolizumab and durvalumab, in combination with traditional chemotherapy, has marked a significant advancement, demonstrating improved overall survival and progression-free survival compared to chemotherapy alone. Despite these advancements, the prognosis for extensive-stage SCLC (ES-SCLC), the more advanced form of SCLC, remains poor, highlighting the critical need for ongoing research and the development of novel therapeutic strategies. New treatment modalities, such as lurbinectedin and anti-Delta-like Canonical Notch Ligand 3 antibodies, are now included in the treatment options for refractory SCLC, and many more treatment strategies involving combination therapies are being studied. Advances in molecular profiling and the identification of biomarkers are aiding in the development of personalized treatment approaches. This review focuses on these recent advancements and emerging strategies in the treatment of ES-SCLC.