onc brain

Single-arm expansion cohort of the CHRYSALIS-2 program, n=49, 1L atypical EGFR-mutated advanced NSCLC. Median follow-up 31.3 mo. No randomised comparator arm.

Treatment-naive advanced NSCLC harbouring an atypical (uncommon) EGFR mutation. Baseline strata shown on the swimmer plot include age ≥65y, Asian ancestry and CNS involvement; per-stratum counts are not reported in source.

IV amivantamab (EGFR/MET bispecific) plus lazertinib (third-generation EGFR TKI). No chemotherapy backbone. Median duration of treatment 13.3 months (range <0.1-53.2), with 39% of 1L participants still on treatment beyond 2 years.

Median OS 41.0 mo (95% CI 27.7-NE), described by the presenters as roughly 3.5 years. The upper CI bound is not estimable, so the point estimate is anchored on the lower bound of 27.7 mo.

Reported only as consistent with prior reports, no new safety signals with longer follow-up. No grade 3+ rates, infusion-reaction rates or dermatologic AE rates appear in the source.

The atypical EGFR label pools biologically distinct alterations (G719X, S768I, L861Q and compound variants) whose single-agent TKI sensitivity differs; n=49 cannot resolve per-variant benefit, and the curator's read of no variant-outcome association is an absence of signal in a small cohort, not evidence of uniformity. No comparator, so the 41.0 mo median cannot be positioned against afatinib or osimertinib series in the same population.

Atypical EGFR is the part of the EGFR-mutant space where no regimen is settled, so a 41.0 mo median in 49 pts is meaningful as a benchmark even without randomisation. The practical question this leaves open is whether the bispecific's added toxicity and IV schedule are justified over an oral TKI alone, which this design cannot answer.

Single-arm n=49 expansion cohort, no randomised comparator against afatinib or osimertinib in atypical EGFR. Maturity gate: single-arm never reaches confirmatory.

Randomised phase II, N=224, asandeutertinib (n=111) vs osimertinib (n=113). Endpoints read by BICR. Follow-up duration, stratification factors and alpha allocation are not reported in the source slide.

First-line EGFR-mutated NSCLC with brain metastases. The source does not state lesion number, size, symptom status, or whether prior CNS radiotherapy was permitted, which is the eligibility gate an RT reader needs.

Intracranial ORR by BICR is the headline, with intracranial PFS and overall PFS reported alongside. No overall survival data in source.

Any TRAE 99.1% vs 95.6%; serious TRAE 10.8% vs 7.1%. The excess serious-event rate is small in absolute terms but sits on a phase II denominator, and no organ-level breakdown is given in source.

The intracranial separation (HR 0.46) is larger than the systemic one (HR 0.64), which points at CNS penetration rather than a general potency gain as the mechanism. For radiation oncology the question is whether that CNS margin is durable enough to defer SRS in asymptomatic pts; a phase II with unreached medians and no OS cannot answer it.

Phase II, conference-slide source only; no OS, borderline overall-PFS p, and no reported CNS-RT or prior-RT stratification. Needs phase III before displacing osimertinib.

Randomized, multicenter, open-label phase 3 (NCT06448312), 1:1, N=413. Stratified by histology (squamous vs non-squamous), PD-L1 TPS (1-49% vs ≥50%), and ECOG (0 vs 1). Median follow-up 10.5 months at this analysis.

Locally advanced stage IIIB/IIIC or metastatic stage IV NSCLC with no prior systemic antitumor therapy. Required PD-L1 TPS ≥1% by IHC 22C3 central lab, no sensitizing EGFR or ALK alteration, ECOG 0 or 1.

Sac-TMT 4 mg/kg Q2W plus pembrolizumab 400 mg versus pembrolizumab 400 mg Q6W alone, until progression or unacceptable toxicity. Pembro was capped at a maximum of 18 cycles in both arms. One pt in the pembro group never received assigned treatment.

Primary: PFS by BICR. Key secondary: OS. Other secondary: investigator-assessed PFS, ORR, DCR, DOR, safety. The updated efficacy boundary at the actual 194 PFS events was 0.0174 (2-sided).

PFS crossed its boundary at p<0.0001. OS was descriptive at the PFS interim, HR 0.55 (0.36, 0.85) with both medians not reached and only 33 vs 54 deaths.

The pembro-alone control performed as expected for an all-comers TPS ≥1% population, with the TPS ≥50% arm reaching 9.5 mo and the TPS 1-49% arm 4.3 mo, consistent with the KEYNOTE-042 signal that low-expressors gain least from single-agent IO. This is the setting where chemo-IO has historically been chosen, so the trial tests whether an ADC can occupy that slot instead of platinum doublet chemotherapy.

No toxicity data in the source, which is the decisive missing piece for a doublet whose entire premise is avoiding chemotherapy. The comparator is pembro monotherapy rather than the chemo-IO most oncologists actually give at TPS 1-49%, so the PFS gap partly measures a weak control rather than a strong experimental arm.

An HR of 0.35 with a median not reached is a large PFS effect, and the OS point estimate moves in the same direction, but neither settles whether sac-TMT plus pembro beats the regimen it would actually replace. The larger effect in TPS 1-49% (HR 0.28) than TPS ≥50% (HR 0.47) is the expected pattern when the control arm is weakest in the low-expressors, not evidence of a biomarker-selected ADC effect.

PFS interim of an open-label phase 3; OS descriptive at 10.5 mo f/u with both medians NR. No safety data in source, and no comparison vs pembro + chemo.

Pooled analysis of 1687 pts treated with single-fraction SABR at three centres (Peter MacCallum, Cleveland Clinic, Roswell Park): 1200 primary NSCLC and 487 pulmonary oligometastases. Whether the contributing cohorts were prospective or retrospective is not stated in source.

Eligibility, operability, tumour size and central vs peripheral location are not reported in source. Cohort mix differs sharply by centre: Roswell Park supplied 401 of the NSCLC pts but only 34 oligomet pts, while Peter Mac supplied 283 of 487 oligomet pts.

Single fraction throughout, but the prescribed dose is not reported in source. Without it the outcome cannot be mapped onto a schedule a reader could write, which is the one parameter that would carry this into planning.

No primary endpoint is stated in the source. Reported outcomes are local control, freedom from local failure, PFS, OS and adverse events, each descriptive rather than tested against a comparator.

Local control 90-93% at 2 years across both cohorts, with isolated local or locoregional failure described as very uncommon. Survival separates by cohort while local outcome does not.

AE reporting covers 789 primary NSCLC pts only, with no Roswell Park data and no oligometastasis toxicity in source. Within that subset chest wall pain and pneumonitis dominate and G3+ events stay at 2.9%.

Single-fraction SABR already carries randomised support: RTOG 0915 in peripheral early-stage NSCLC and SAFRON II in pulmonary oligometastases, both randomised single against multi-fraction schedules. This series adds scale and follow-up at three high-volume centres, which is what a non-randomised dataset can contribute, and no comparator.

Toxicity rests on 789 of 1687 pts, with one centre absent from the AE table and the oligometastatic cohort not represented in it at all. Centre mix is uneven, so pooled rates carry each centre's own selection rather than a common one.

The question the thread raises, whether one-stop SABR should be used more often, is not the question this dataset answers. What it does show is that local control near 90-93% and G3+ toxicity near 3% hold at scale outside a protocol, which is the usual worry about a schedule with no second chance. The unreported dose sits between that reassurance and a prescription.

Pooled uncontrolled series across three centres, no multi-fraction comparator and no stated design; dose unreported, so outcomes cannot be tied to a prescription.