Journal of Clinical Oncology最新文献

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations.

Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date.

Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations.

Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Six new RCTs were identified in the latest search of the literature to date.

Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Purpose: BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer.

Methods: We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2, a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer.

Results: A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer-related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001).

Conclusion: After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.

Purpose: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive multiple effective lines of therapy, underscoring the need for novel frontline strategies.

Methods: In this phase II, open-label, single-arm trial (ClinicalTrials.gov identifier: NCT05860036), patients received 3-4 cycles of protocol-allowed induction, followed by B-cell maturation antigen (BCMA) CAR-T infusion, and subsequent consolidation and lenalidomide maintenance. The primary end point was the rate of minimal residual disease (MRD) negativity (10^-5) at Month three postinfusion.

Results: Between April 4, 2023, and December 26, 2024, 43 patients were screened, 40 were enrolled, and 36 received infusion (median age, 68 years [46-75]). In the infused cohort, the MRD negativity rate at Month three postinfusion was 100% (36 of 36; 95% CI, 90.3 to 100.0). With a median follow-up of 15.8 months postinfusion (range, 4.3-26.0), no MRD recurrence was observed. The complete response rate (CRR) increased from 33.3% (12 of 36; 95% CI, 18.6 to 51.0) preinfusion to 69.4% (25 of 36; 95% CI, 51.9 to 83.7) at Month 3% and 94.4% (34 of 36; 95% CI, 81.3 to 99.3) at last follow-up. The most common grade 3 to 4 adverse events were transient cytopenia, including lymphopenia (100%), neutropenia (88.9%), leukopenia (80.6%), thrombocytopenia (19.4%), and anemia (8.3%). Cytokine release syndrome occurred in 52.8% of patients (all grade 1 to 2), immune effector cell-associated neurotoxicity in 5.6% (all grade 1), and infections in 30.6% (grade ≥3 in 19.4%). No deaths or disease progressions occurred by cutoff.

Conclusion: Frontline BCMA CAR-T therapy induces deep, rapid, and durable remissions with a manageable safety profile in the NDMM population ineligible for or not proceeding to ASCT. These findings support its investigation as a potentially practice-changing strategy for this population.

Purpose: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer.

Methods: We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer.

Results: PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework.

Conclusion: PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

Purpose: To provide updated recommendations for immunotherapy and targeted therapy for patients with advanced gastroesophageal cancer.

Methods: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

Results: Twelve newly published or updated phase III randomized controlled trials met the inclusion criteria for the systematic review.

Recommendations: The target population for these recommendations is patients with unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. Results from testing for actionable biomarkers should be available as soon as possible to inform treatment decision making. Immunotherapy with doublet chemotherapy is recommended for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma or squamous cell carcinoma and PD-L1 expression ≥1; patients with higher PD-L1 expression are more likely to benefit from immunotherapy. Zolbetuximab is recommended for patients with gastroesophageal adenocarcinoma, PD-L1 <1, and positive CLDN18.2 expression. Patients with dual PD-L1 and CLDN18.2 positivity should engage in shared decision making, considering the factors outlined in the guideline. Doublet chemotherapy alone is recommended for patients who are not positive for actionable biomarkers or are not considered candidates for targeted therapy or immunotherapy. For patients with pMMR/MSS HER2-positive gastric/gastroesophageal junction (GEJ) adenocarcinoma, trastuzumab and doublet chemotherapy is recommended; for patients with PD-L1 expression ≥1, the addition of pembrolizumab is recommended. Immunotherapy alone or with doublet chemotherapy is recommended for patients with mismatch repair deficient/microsatellite instability-high gastroesophageal cancer. Second-line therapy options include ramucirumab with paclitaxel, trastuzumab deruxtecan for HER2-positive gastric/GEJ adenocarcinoma, and immunotherapy for PD-L1 ≥1 esophageal squamous cell carcinoma after first-line combination chemotherapy without immunotherapy.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Purpose: Smoking cessation after a cancer diagnosis improves survival, but widespread adoption of evidence-based cessation assistance has not been demonstrated. American College of Surgeons' accredited cancer programs participated in the nationwide Beyond ASK quality improvement (QI) initiative to increase the proportion of currently smoking patients with cancer offered cessation assistance as part of cancer care delivery.

Methods: A national QI project was employed between January 2023 and January 2024 following the Plan-Do-Study-Act methodology, and five longitudinal surveys were administered. Participating programs received educational webinars, an online practice change package that contained information about evidence-based smoking assessment and cessation assistance tools, training opportunities, and electronic health record guidance. Primary outcomes included identification of current smoking among patients with newly diagnosed cancer and rate of providing cessation assistance among currently smoking patients.

Results: A total of 324 programs (164 [50.8%] community programs) enrolled in Beyond ASK. Participation rates were high with 300 (92.6%) programs completing all five surveys. Among 446,015 reported patients newly diagnosed with cancer, 52,794 (11.8%) were identified as currently smoking of which 33,638 (63.7%) received cessation assistance. The mean assist rate increased from 48.0% (95% CI, 43.7 to 52.2) at baseline to 67.5% (95% CI, 63.6 to 71.3) at final. Full adoption was reported by 65.4% of programs. Delivery of cessation assistance increased over time for in-office brief counseling (33.9%-65.8%, P = .0002), in-office behavioral counseling (7.1%-18.5%, P = .02), referral to in-house program (14.5%-27.3%, P = .02), referral to community program (12.1%-29.5%, P = .002), and referral to web-based programs (12.2%-33.9%, P = .0002).

Conclusion: Scaled improvement in smoking cessation assistance across accredited cancer programs is feasible and achievable relatively quickly. Findings provide a framework to guide national adoption for smoking cessation assistance as standard care for all patients with newly diagnosed cancer.

Purpose: Critical guidance on selecting haploidentical donors for pediatric patients is lacking. It is unclear whether parents, siblings, and extended family affect acute and chronic graft-versus-host disease (aGVHD and cGVHD) differently.

Methods: We analyzed 1,069 pediatric (<19 years) recipients of hematopoietic cell transplant during 2013-2019. Primary end points were aGVHD frequency at 100 days and cumulative incidence of cGVHD at 2 years, assessed by donor age (<18 years, 18-35, >35 years) and donor relationship, with multivariable analysis.

Results: Donor age: Increased grade II-IV aGVHD occurred with older donors: >35 years (31%, odds ratio [OR], 1.7 [95% CI, 1.0 to 2.8]; P = .05) and 18-35 years (23%, OR, 2.5 [95% CI, 1.5 to 4.2]; P = .0003), versus < 18 years (15%, reference OR, 1). Increased cGVHD occurred in older donors: >35 years (incidence 30% [95% CI, 28 to 32]; hazard ratio [HR], 2.2 [95% CI, 1.3 to 3.9]; P = .004) and 18-35 years (incidence 26% [95% CI, 23 to 29]; HR, 2.1 [95% CI, 1.3 to 3.5]; P = .0028) compared with <18 years (incidence 16% [95% CI, 12 to 20]; reference HR, 1). Donor relationship: Patients with parental donors had higher aGVHD risk than siblings (mother: OR, 1.9 [95% CI, 1.3 to 2.8]; P = .001; father: OR, 1.7 [95% CI, 1.1 to 2.5]; P = .009). Patients with maternal donors had a significantly higher risk of cGVHD than paternal (HR, 2.3 [95% CI, 1.6 to 3.3]; P < .0001) and sibling donors (HR, 2.3 [95% CI, 1.7 to 3.4]; P < .0001). Age-relationship interaction: Maternal donors were associated with more GVHD than siblings, regardless of age (aGVHD II-IV, mothers >35 years, HR, 2.53 [95% CI, 1.46 to 4.41]; mothers 18-35 years, HR, 2.05 [95% CI, 1.14 to 3.69]) (cGVHD: mothers >35 years, HR, 3.10 [95% CI, 1.72 to 5.60]; mothers 18-35 years, HR, 3.35 [95% CI, 1.8 to 6.25]).

Conclusion: Donors <18 years are associated with reduced aGVHD and cGVHD, whereas maternal donors are associated with increased cGVHD risk. For pediatric patients, sibling donors should be considered to reduce GVHD.