Journal of Clinical Oncology最新文献

Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications.

Results: A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials.

Recommendations: Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor v metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.

Purpose: Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.

Methods: In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m² once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m² once on day 1 or paclitaxel 80 mg/m² once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.

Results: Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.

Conclusion: The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC.

Purpose: To provide evidence-based recommendations to practicing physicians and others on the management of pleural mesothelioma (PM).

Methods: ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pathology, cancer genetics, and advocacy experts to conduct an updated literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2016 through 2024. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: The literature search identified 110 additional relevant studies to inform the evidence base for this guideline.

Recommendations: Evidence-based recommendations were developed for surgical cytoreduction, immunotherapy, chemotherapy, pathology, and germline testing in patients with PM.Additional information is available at www.asco.org/thoracic-cancer-guidelines.

Purpose: Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non-small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.

Methods: Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety.

Results: A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively.

Conclusion: Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.

Purpose: Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood.

Methods: We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model.

Results: Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m² (HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]).

Conclusion: Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.

Purpose: In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.

Methods: ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL. Patients received BV or placebo once every 3 weeks, Len once daily, and R once every 3 weeks. The primary end point was overall survival (OS), and secondary end points included investigator-assessed progression-free survival (PFS) and objective response rate (ORR). A prespecified interim analysis was performed after 134 OS events, with two-sided P = .0232 as the efficacy boundary.

Results: Patients (N = 230) were randomly assigned to receive BV + Len + R (n = 112) or placebo + Len + R (n = 118). Two patients in the placebo arm did not receive treatment. With a median follow-up of 16.4 months, the median OS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (hazard ratio, 0.63 [95% CI, 0.45 to 0.89]; two-sided P = .009). The median PFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (hazard ratio, 0.53 [95% CI, 0.38 to 0.73]; two-sided P < .001). The ORR was 64% ([95% CI, 55 to 73]; two-sided P < .001) with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; complete response rates were 40% and 19%, respectively. Treatment-emergent adverse events (AEs) occurred in 97% of patients in both arms. In both arms, the most common treatment-emergent AEs were neutropenia, thrombocytopenia, diarrhea, and anemia.

Conclusion: BV + Len + R demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.