Journal of Clinical Oncology最新文献

A pediatric oncologist's experience of a patient's death through the new lens of motherhood.

We report 5-year results of the phase III randomized TRIPLETE study. Eligible patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) received first-line modified fluorouracil, leucovorin, oxaliplatin (mFOLFOX)/panitumumab (control group, n = 217) versus modified fluorouracil, leucovorin, oxaliplatin, irinotecan (mFOLFOXIRI)/panitumumab (experimental group, n = 218). We present overall survival (OS) and updated outcomes in the intention-to-treat population. The median follow-up was 60.2 months (IQR, 49.3-70.0). The median OS was 41.1 and 33.3 months for experimental and control groups, respectively (hazard ratio [HR], 0.79 [95% CI, 0.63 to 0.99]; P = .049). OS outcomes favored the experimental group regardless of clinical features. No differences in objective response rate (primary end point; 75%/78%, odds ratio, 0.84 [95% CI, 0.54 to 1.31]; P = .442), early tumor shrinkage rate (P = .954), depth of response (P = .573), no residual tumor resection rate (P = .329), and progression-free survival (HR, 0.95 [95% CI, 0.78 to 1.16]; P = .606) were confirmed. Among patients alive at the time of disease progression, the median postprogression survival was 24.6 and 17.7 months for experimental and control groups, respectively (HR, 0.79 [95% CI, 0.62 to 1.01]; P = .062). Similar proportions of patients in both groups received subsequent lines of therapy (control/experimental: second line 73%/71%, third line 51%/49%, fourth line 31%/32%), as well as nonpalliative locoregional treatments (control/experimental: 16%/16%). Upfront mFOLFOXIRI/panitumumab significantly improves OS compared with mFOLFOX/panitumumab in patients with RAS/BRAF wild-type mCRC.

KMT2A-rearranged infant ALL (KMT2A-r ALL) has a poor prognosis. Adding blinatumomab, a bispecific T-cell engager targeting CD19, to standard chemotherapy for infants with KMT2A-r ALL improved short-term outcomes. Here, we present long-term results, toxicity, and pharmacokinetics of blinatumomab from this study. Thirty infants received Interfant-06 protocol chemotherapy with one additional postinduction blinatumomab course. Disease-free survival (DFS) and overall survival (OS) were compared with a historical Interfant-06-selected cohort without blinatumomab. Infection and administration of intravenous immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF) were documented. Blinatumomab's steady-state concentration (Css) and clearance (CL) were analyzed. The median follow-up was 4.2 years (range, 3.2-6.0). Blinatumomab significantly improved outcomes compared with controls, with a 4-year DFS of 83.3% versus 44.0% and a 4-year OS of 93.3% versus 60.2%. No infection-related fatality occurred postinduction, in contrast to 4% in Interfant-06. IVIg was administered in 19 (63%) patients, and G-CSF in five (17%). The mean Css of blinatumomab was 706 ± 194 pg/mL/d, and the median CL was 0.89 L/h/m² (range, 0.57-2.66). Adding blinatumomab to standard treatment for infants with KMT2A-r ALL resulted in sustained improvement in outcome. Pharmacokinetics were comparable across pediatric age groups. The benefit of blinatumomab in frontline therapy remains promising and awaits further confirmation in ongoing trials.

Randomized trials provide evidence for regulatory and clinical decision making in oncology. However, trials cannot answer every important clinical question. Evidence gaps often persist in under-represented or small patient populations and for questions about head-to-head comparisons of active treatments, complex treatment strategies (including treatment sequencing and other dynamic treatment strategies), and long-term or rare outcomes. To address these questions, clinicians and researchers increasingly turn to observational (real-world) data. The target trial framework provides a systematic approach for designing observational analyses that attempt to emulate a hypothetical pragmatic trial. This process requires that investigators specify the key components of the causal question as elements of the target trial protocol: eligibility criteria, treatment strategies, assignment procedures, follow-up, outcomes, and causal contrasts. Explicitly emulating the target trial helps investigators avoid common study design flaws that can lead to immortal time and selection bias. Although the target trial framework helps to avoid such design-related biases, it cannot eliminate biases due to inherent data limitations, such as confounding and measurement error. Here we review target trial emulation to supplement evidence from randomized trials and inform regulatory and clinical decision making in oncology. Understanding the strengths and limitations of the target trial framework improves the integration of real-world evidence into modern cancer care.