American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung carcinoma (NSCLC) comprising over 85% of cases. Advances in molecular diagnostics and precision oncology have shifted treatment toward mutation-driven strategies, resulting in significantly improved patient outcomes. This review synthesizes current evidence on the most clinically relevant genetic alterations in NSCLC and their corresponding targeted therapies, including epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, ROS1 fusions, BRAF V600E mutations, MET exon 14 skipping mutations, RET and NTRK fusions, HER2 alterations, and KRAS G12C mutations. We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.

Objectives: Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is rapidly growing with poor outcomes if left untreated. Research evidence indicates that chemotherapy-free regimens can improve outcomes of HER2-positive early breast cancer while maintaining high oncogenic safety. The main objective of our study was to examine the efficacy and safety of chemotherapy-free regimens in patients with HER2-positive early breast cancer.

Methods: A systematic literature search was conducted using the PubMed, CENTRAL, Google Scholar, and Embase databases to identify relevant randomized trials published until July 2024.

Results: Five randomized trials, including 1489 patients with early-stage HER2-positive breast cancer, met the inclusion criteria for this meta-analysis. The pooled results showed that about 26.1% (182/698) of patients receiving chemo-free therapies achieve pathologic complete response (pCR). However, the subgroup analysis revealed that patients treated with trastuzumab plus pertuzumab and those treated with HER2-directed drugs plus endocrine therapy had significantly inferior pCR than those receiving chemotherapy combined with anti-HER2 drugs (OR: 0.22, P=0.0002 and OR: 0.25, P<0.00001). The meta-analytic results also demonstrated that patients receiving chemo-free therapies have high 3-year and 5-year invasive disease-free survival (iDFS) (95.40% and 85.71%) and 5-year event-free survival (EFS) (81.13). Regarding safety, the pooled results revealed that the discontinuation rates due to adverse events were statistically similar between the 2 groups (OR: 0.29, P=0.18).

Conclusions: Chemotherapy-free regimens demonstrate promising responses and survival outcomes in patients with HER2-positive early breast cancer. However, the combination of anti-HER2 drugs with chemotherapy still demonstrates superior overall clinical outcomes.

Objectives: Despite a good response to first-line chemotherapy, small-cell lung cancer (SCLC) has high relapse rates and a poor prognosis. We conducted a systematic review and meta-analysis to assess the role of immune checkpoint inhibitors (ICIs) in the treatment of extended stage SCLC (ES-SCLC), in different lines of therapy.

Methods: Medline (PubMed), EMBASE, and Cochrane Library databases between January 2010 and March 2025 and conference proceedings between 2018 and 2025 were searched for RCTs assessing ICIs versus chemotherapy in patients with ES-SCLC. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and grade 3+ adverse events. Pooled hazard ratios (HR) for OS and PFS were meta-analyzed using the generic inverse variance method, and random-effect models were used to compute pooled estimates. Subgroup analyses compared survival by line of therapy, sex, age, and ECOG status.

Results: ICIs decreased risk of death by 19% (HR: 0.81, 95% CI: 0.76-0.86). OS benefit was regardless of age, sex, or ECOG, but only in first-line treatment. ICIs decreased the risk of disease progression by 22% (HR: 0.78, 95% CI: 0.67-0.91), with PFS benefit restricted to first-line treatment with a detrimental effect in the second line. ICIs improved ORR (OR: 0.79, 95% CI: 0.66-0.95), but were associated with increased grade 3+diarrhea (OR: 3.63, 95% CI: 1.46-9.02).

Conclusions: ICIs conferred efficacy benefits and an acceptable safety profile in the treatment of patients with ES-SCLC in the first-line, but should not be used in the second-line as single agents. Biomarkers predicting long-term benefit are needed to further improve outcomes.

Objectives: There is an urgent need for effective second line treatments for advanced upper gastrointestinal (UGI) cancers. Ramucirumab and paclitaxel (Ram-Pac) has long been the standard therapy; however, this regimen is often complicated by cumulative neuropathy. FOLFIRI-Ramucirumab (FOLFIRI-Ram) may be an alternative second line option but real-world data to support its use are limited.

Methods: The deidentified Flatiron Health Research Database was queried for patients treated for unresectable or metastatic UGI cancers with second line Ram-Pac or FOLFIRI-Ram from January 2011 to June 2024. Study cohorts were propensity score matched 1:6 (FOLFIRI-Ram:Ram-Pac) from key clinical and laboratory characteristics. The endpoints of interest were overall survival (OS) and real-world time to treatment discontinuation (rwTTD).

Results: Of 15,908 patients with UGI cancer, 631 received second line Ram-Pac and 40 received second line FOLFIRI-Ram. After matching, 40 FOLFIRI-Ram and 240 Ram-Pac patients were included. Median OS was 9.7 months with FOLFIRI-Ram (95% CI: 6.9-12.3) and 7.7 months with Ram-Pac (95% CI: 6.2-8.8), with a hazard ratio (HR) for death of 0.74 with FOLFIRI-Ram versus Ram-Pac (95% CI: 0.50-1.11, P=0.14). The median rwTTD with FOLFIRI-Ram was 5.2 months (95% CI: 4.1-6.2), compared with 3.7 months with Ram-Pac (95% CI: 3.2-4.3), HR for treatment discontinuation =0.70 (95% CI: 0.48-1.00, P=0.048).

Conclusions: In a real-world propensity-score matched analysis, no survival difference was noted with the combination of FOLFIRI-Ram compared with Ram-Pac; however, FOLFIRI-Ram was associated with a significantly longer rwTTD. Altogether, these data suggest FOLFIRI-Ram is a potential alternative for second line treatment of UGI cancers.

Objectives: Chemotherapy interruptions are a frequent event during treatment of solid tumors and have been associated with adverse survival outcomes. Our objective was to determine the impact of intercycle delay during first-line systemic chemotherapy on survival in patients with metastatic (stage IVB) or recurrent cervical cancer.

Methods: A retrospective cohort study identified patients with metastatic or recurrent cervical cancer treated at our institutions. Demographics, clinicopathologic information, first-line chemotherapy regimens with associated intercycle delays, and outcome measures were abstracted from medical records. Delays were categorized as modifiable (social determinants of health, logistics, treatment break) or nonmodifiable (cytopenias, organ dysfunction, chemotherapy reaction, infection, ECOG status). Data were analyzed using descriptive statistics, Kaplan-Meier survival estimate, and log-rank tests to calculate significance ( P <0.05).

Results: Two hundred ten patients were evaluable for this study. 178 (85%) had at least one intercycle delay. One thousand eight hundred seventy-three chemotherapy cycles were completed with 701 (37%) delays. There was an equal proportion of modifiable (352/701) and nonmodifiable (349/701) delays. Patients with one or more intercycle delay had a longer median PFS (13 mo, IQR: 7 to 24) compared with those without delays (8 mo, IQR: 4 to 17), P =0.042. PFS stratified by subgroups revealed patients with modifiable delays as having improved PFS ( P =0.036) and nonmodifiable subgroup trending towards improved PFS ( P =0.058) compared with patients with no delays. There was no PFS difference between the modifiable and nonmodifiable subgroups and no overall survival differences.

Conclusions: Intercycle delays during first-line systemic chemotherapy for metastatic or recurrent cervical cancer do not have an adverse effect on survival.

Objectives: The National Comprehensive Cancer Network guidelines recommend tumor phenotyping for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 at initial breast cancer diagnosis, with repeat biopsy considered at disease progression. This study assessed the frequency, timing, regional variation, and predictors of repeat biopsies among patients with metastatic breast cancer (mBC) treated at community oncology practices in the United States.

Methods: A weighted random sample of 911 mBC patients was selected from 15 practices within the ONCare Alliance network. The data included demographics, clinical characteristics, number and types of biopsies, and associated findings. Multivariate negative binomial regression, adjusted for disease duration, was used to identify predictors of biopsy frequency.

Results: Among the cohort, 42.2% had a history of early-stage disease, while 57.8% were diagnosed with de novo stage IV mBC. After adjusting for disease duration, patients with prior early-stage disease underwent significantly more biopsies (mean: 3.9; 95% CI: 3.7-4.0) than those with de novo mBC (mean: 2.2; 95% CI: 2.1-2.3; P<0.001). Factors associated with fewer biopsies included non-Black, non-Asian minority status (RR=0.80, P<0.001), longer time to metastatic progression (RR=0.93, P<0.001), poor performance status, and geographic region.

Conclusions: A substantial proportion of patients with mBC, particularly those with de novo disease, did not undergo repeat biopsy at progression. These findings reveal disparities in biopsy practices and underscore the need for improved adherence to guideline-based care in community oncology settings.

Objectives: Synovial sarcoma (SS) of the abdomen and pelvis is a rare and understudied condition. This study aimed to evaluate survival outcomes, assess calculated versus observed outcomes, and describe radiographic features among patients with localized abdominal/pelvic SS.

Methods: A retrospective chart review of 58 patients diagnosed with localized abdominal/pelvic SS between 1992 and 2022 was performed. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were assessed. Sarculator-predicted 5-year OS and disease-free survival (DFS) were compared with observed outcomes.

Results: Twenty-four (41%) patients had tumors located in the extra-abdominal/pelvic region, and 34 (59%) had tumors located in the intra-abdominal/pelvic region. Most of the patients were female (62%). Survival outcomes revealed a median OS: 5.5 years, 5-year OS: 53%, median MFS: 1.5 years, and 5-year MFS: 32%. Patients with intra-abdominal/pelvic tumors had significantly worse MFS than those with extra-abdominal/pelvic tumors (median 1.3 vs. 2.7 y; P =0.023). Larger tumor size (≥5 cm MFS HR: 4.20, 95% CI: 1.48-11.95), poorly differentiated histology (MFS HR: 2.92, 95% CI: 1.13-7.53), and positive/unknown margins (OS HR: 2.96, 95% CI: 1.29-6.78; LRFS HR: 6.61, 95% CI: 1.65-26.50; MFS HR: 2.45, 95% CI: 1.23-4.89) were associated with worse outcomes. Sarculator-predicted and observed 5-year OS (49% vs. 52%) and DFS (30% vs. 26%) were consistent. Imaging features such as cystic changes and calcification were more frequent in larger and monophasic tumors.

Conclusions: In localized abdomen/pelvic SS patients, tumor size, location, and surgical margins are critical prognostic factors. Sarculator may aid in risk stratification.

Acute myeloid leukemia (AML) continues to pose a major hurdle in hematologic oncology, driven by its genetic complexity and tendency to resist standard therapies. Even with progress in treatment-such as high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT)-outcomes remain unsatisfactory for many patients. In recent years, immunotherapy has emerged as an appealing strategy to improve survival by strengthening the body's own anti-leukemia defenses. Natural killer (NK) cells, a critical component of innate immunity, have shown strong potential for directly eliminating AML cells without prior antigen exposure. This review outlines the role of NK cells in AML immune surveillance, mechanisms by which their function becomes impaired in the disease, and the current therapeutic approaches harnessing NK cells in AML management. We also discuss key obstacles and opportunities, including strategies to boost NK cell activity, counter immune escape, and improve treatment durability. Continued investigation is essential to refine NK cell-based therapies and bring patient-tailored immunotherapeutic options into broader clinical use.

Objectives: The Hispanic-American population is the nation's second-largest racial/ethnic group and the second most rapidly growing population. Radiation therapy (RT) is an indispensable, highly effective treatment for cancer; therefore, any barriers impairing RT access may yield deleterious consequences for Hispanic-Americans. The Navigator-Assisted Hypofractionation (NAVAH) program was developed to optimize RT access for all cancer patients. A key component of NAVAH is the use of culturally sensitive surveys to assess the impact of patient navigation before and after RT. We present initial findings from a Spanish-language cancer support group comprised of Hispanic-American patients as a baseline before implementation of NAVAH at our institution.

Methods: A previously validated, Spanish-language, culturally sensitive survey was implemented to identify barriers to cancer care among Hispanic Americans. Participants were recruited to complete interviewer-administered surveys between monthly group visits. Surveys assessed several domains, including acceptability, accessibility, accommodation, affordability, and availability.

Results: Eight cancer survivors completed surveys in person. Interviewees reported a positive but variable assessment of the availability, accommodation, and accessibility domains, suggesting that services may adequately meet patients' needs and preferences. However, responses in the acceptability domain reflected a strong perception of disparities and ethnic bias. In addition, feedback in the affordability domain indicates a heightened vulnerability to financial toxicity within this population.

Conclusions: These initial findings from the NAVAH program underscore the persistent challenges faced by Hispanic-American cancer patients, particularly in the realms of perceived discrimination and financial toxicity. These insights emphasize the necessity for culturally sensitive interventions, such as bilingual patient navigation programs, to address and mitigate the multifaceted barriers encountered by Hispanic-American patients. The NAVAH program's approach of incorporating culturally attuned surveys and support mechanisms represents a promising step toward optimizing equity in cancer treatment. Moreover, these early impressions pave the way for further investigation involving patients actively receiving RT.

Objectives: Esophageal cancer (EC) often presents with dysphagia due to tumor obstruction. Esophageal stenting has the potential of palliating dysphagia, improving nutrition, preventing aspiration, and improving quality of life (QoL) but may be associated with risks. The present systematic review and guidelines are intended to assist treatment decision-making when considering stent placement in patients with EC based on the available evidence.

Methods: Using the population, intervention, comparator, outcome, timing and study design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective phase II-III trials and retrospective analyses published between January 1, 2010 and December 3, 2024 in the Ovid Medline database. These references were assessed by American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of the use of stents.

Results: ARS AUC recommendations include (1) esophageal stenting is usually not appropriate in patients with early-stage EC in whom upfront surgery is planned; (2) esophageal stenting is usually not appropriate in patients with locally-advanced EC in whom neoadjuvant/perioperative therapy and esophagectomy or definitive chemoradiation is planned; (3) esophageal stenting may be appropriate in the setting of metastatic EC, especially in patients with short life expectancy with limited treatment options; (4) esophageal stenting is usually not appropriate for benign stricture following curative-intent therapy; (5) esophageal stenting is usually not appropriate for locally recurrent tumor in the setting of prior radiation; and (6) esophageal stenting is usually appropriate for management of tracheoesophageal fistula before curative-intent treatment.

Conclusions: This ARS AUC summary provides guidelines for the use of esophageal stents in patients with EC provides based on available evidence.