30-Second Takeaway
- Culmerciclib plus fulvestrant markedly prolongs PFS and increases responses in pretreated HR+/HER2– advanced breast cancer, with manageable diarrhea and neutropenia.
- PD-1–based salvage before ASCT is linked to substantially better 2-year PFS in relapsed/refractory classical Hodgkin lymphoma.
- After EGFR-TKI failure in NSCLC, antibody–drug conjugates, especially sacituzumab tirumotecan, outperform chemotherapy for PFS and OS.
- Serial tumor-informed ctDNA assays detect colorectal cancer recurrence more sensitively than tumor-agnostic tests without higher false positives.
- Perioperative ctDNA across HCC and endometrial cancer strongly stratifies recurrence risk, informing surveillance and adjuvant-trial design.
Week ending December 20, 2025
Post-resistance strategies, ctDNA risk tools, and trial endpoints: concise updates across solid tumors and lymphoma
Culmerciclib plus fulvestrant significantly extends PFS in pretreated HR+/HER2– advanced breast cancer
In this double-blind phase 3 trial, 293 previously treated HR-positive, HER2-negative advanced breast cancer patients were randomized 2:1 to culmerciclib plus fulvestrant versus placebo plus fulvestrant. Culmerciclib significantly prolonged PFS versus control (16.6 vs 7.5 months; HR 0.36; 95% CI 0.26–0.51; P < 0.001). Objective response rate was higher with culmerciclib (40.2%; 95% CI 33.3–47.5) than with placebo (12.1%; 95% CI 6.4–20.2). Overall survival remains immature at 13.8 months’ median follow-up, while diarrhea and neutropenia were the most common, generally manageable toxicities.
PD-1–based salvage before ASCT improves post-transplant PFS in relapsed/refractory classical Hodgkin lymphoma
This multicenter retrospective cohort included 1,280 relapsed or refractory classical Hodgkin lymphoma patients undergoing ASCT from 2010–2022 without frontline PD-1 exposure. Twenty-five percent received PD-1 inhibitors pre-ASCT, 28% received brentuximab vedotin without PD-1, and the remainder received chemotherapy alone. Any pre-ASCT PD-1 exposure was associated with superior 2-year PFS compared with brentuximab-alone or chemotherapy-alone salvage (88.2% vs 70.2% vs 67.4%; p < 0.0001). The PFS advantage persisted among patients in complete response pre-ASCT, and PD-1 use was independently associated with better post-transplant outcomes.
ADCs, particularly sacituzumab tirumotecan, rank best after EGFR-TKI resistance in advanced NSCLC
This Bayesian network meta-analysis pooled 19 randomized trials including 4,039 patients with advanced NSCLC progressing after EGFR-TKIs. Sacituzumab tirumotecan markedly improved PFS (HR 0.20; 95% CrI 0.13–0.30) and OS (HR 0.36; 95% CrI 0.20–0.66) versus conventional chemotherapy. Sacituzumab tirumotecan provided statistically superior PFS versus nearly all other regimens, including immune checkpoint inhibitor– and bispecific antibody–based strategies. Datopotamab deruxtecan and bispecific-antibody regimens also showed favorable efficacy, while amivantamab plus lazertinib with chemotherapy produced more severe adverse events.
Serial tumor-informed ctDNA assays best detect colorectal cancer recurrence after surgery
This diagnostic meta-analysis compared tumor-informed and tumor-agnostic ctDNA assays for recurrence detection in resected early-stage colorectal cancer. With serial sampling, tumor-informed assays had substantially higher sensitivity than tumor-agnostic tests (0.88 vs 0.59; p = 0.001). False-positive rates were similar between strategies, indicating improved sensitivity without loss of specificity. Landmark single-timepoint analyses did not show significant accuracy differences, emphasizing the value of longitudinal testing when feasible.
References
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Additional Reads
Optional additional studies from this edition.