Thoracic / Lung
First RCT on brain RT timing in EGFR/ALK+ mNSCLC challenges reflexive upfront irradiation in asymptomatic BM.
Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC) NCT05236946
ForMetastatic NSCLC, EGFR or ALK mutant, completely asymptomatic BM, ECOG 0-2
TL;DRUpfront brain RT halves icPD (HR 0.35, p<0.001) but OS numerically favors delayed (HR 1.45, 2yr 60% vs 48%) in EGFR/ALK+ mNSCLC.
- First RCT on this question; supports emerging TKI-first approach (osimertinib/alectinib CNS penetration)
| Upfront RT (n=105) | Delayed RT (n=103) | |
|---|---|---|
| Events | 20 | 47 |
| 1-yr cumulative icPD | 8.7% (2.9%, 14.5%) | 25.7% (16.8%, 34.7%) |
| 2-yr cumulative icPD | 21.7% (12.6%, 30.8%) | 50% (39.2%, 60.9%) |
| Sub-HR (95% CI) | 0.35 (0.21, 0.59) | ref |
| p-value | <0.001 | — |
+1 more figure
7 details
- 🔍 Phase III open-label RCT, N=208; EGFR/ALK+ mNSCLC, completely asymptomatic BM, ECOG 0-2
- 🔍 Both arms: TKIs + chemotherapy; delayed arm: RT at intracranial PD or patient request
- 🔍 Stratification: GPA score (0-2 vs >2); synchronous vs metachronous BM
CONSORT flow
- 📊 OS HR 1.45 favoring delayed; 2yr OS 48% upfront vs 60% delayed (secondary endpoint)
- ⚠️ Radiation necrosis: 6% upfront vs 0% delayed
- ⚠️ OS HR p-value not reported in source; trial takeaway: 'timing of RT does not affect survival'
- ⚠️ TKI + chemo backbone may not reflect current osimertinib or alectinib monotherapy practice
- Does icPD reduction with upfront RT translate to QoL or neurocognitive benefit?
- SRS vs WBRT in upfront arm: impact on radiation necrosis rate?
- Which pts (high GPA, many lesions) benefit most from upfront cranial RT?
📚 Sources · 🐦 3 tweets
#ASCO26 | Wait or Treat? Brain RT in EGFR/ALK+ NSCLC
— OncLive.com (@OncLive) May 29, 2026
Presented by Dr Anil Ramakant Tibdewal.
A landmark Phase III randomized trial from @TataMemorial addressed a long-standing question: should asymptomatic brain metastases in oncogene-driven NSCLC receive upfront cranial RT or… pic.twitter.com/lRy9CfyQ8r
Should asymptomatic brain mets await systemic response in front line within EGFR/ALK context? I think yes. Despite reducing icPD, delayed brain RT OS looked better and radiation necrosis didn’t occur vs 6% #ASCO26 pic.twitter.com/O6d7GrvtU4
— Dr Riyaz Shah (@DrRiyazShah) May 29, 2026
No improvement in survival with up front radiation. OS favored delayed radiation with 2y OS 48% with early radiation vs 60% in late (OS HR 1.45). Also, radiation necrosis less common and less severe in delayed arm. Each case unique but delayed approach appealing #ASCO26 pic.twitter.com/wIhjqxhSaq
— Stephen V Liu, MD (@StephenVLiu) May 29, 2026