Clinical Trials Knowledge Base
Lung · SCLC
ES-SCLC 1L IO + chemotherapy
8
From IMpower133 to ETER701 — full evolution of 1L IO era, with Chinese PD-1/PD-L1 and anti-angiogenic combinations
IMPOWER133
atezolizumab + carboplatin + etoposide vs placebo + carboplatin + etoposide
mOS 12.3 vs 10.3 mo (HR 0.70, 95% CI 0.54-0.91, P=0.007); mPFS 5.2 vs 4.3 mo (HR 0.77, 95% CI 0.62-0.96, P=0.02)
Population: Treatment-naive extensive-stage small-cell lung cancer
CASPIAN
durvalumab + platinum-etoposide (EP/EC) vs platinum-etoposide (EP/EC)
mOS 13.0 vs 10.3 mo (HR 0.73, 95% CI 0.59-0.91, P=0.0047); 18-mo OS 34% vs 25%
Population: Treatment-naive extensive-stage small-cell lung cancer
ASTRUM-005
serplulimab (HLX10) + carboplatin + etoposide vs placebo + carboplatin + etoposide
mOS 15.4 vs 10.9 mo (HR 0.63, 95% CI 0.49-0.82, P<0.001); mPFS 5.7 vs 4.3 mo (HR 0.48, 95% CI 0.38-0.59)
Population: Previously untreated extensive-stage small-cell lung cancer
CAPSTONE-1
adebrelimab (SHR-1316) + carboplatin + etoposide vs placebo + carboplatin + etoposide
mOS 15.3 vs 12.8 mo (HR 0.72, 95% CI 0.58-0.90, one-sided P=0.0017)
Population: Treatment-naive extensive-stage small-cell lung cancer (Chinese population)
ETER701
benmelstobart + anlotinib + etoposide + carboplatin (four-drug) vs anlotinib + EC (three-drug) vs double placebo + etoposide + carboplatin (EC alone)
mOS 19.3 vs 11.9 mo for benmelstobart+anlotinib+EC vs EC (HR 0.61, P=0.0002); anlotinib+EC vs EC 13.3 vs 11.9 mo (HR 0.86, P=0.1723, NS)
Population: Treatment-naive extensive-stage small-cell lung cancer (Chinese population)
IMBRELLA-A
atezolizumab monotherapy continuation (post-IMpower133) vs no control (extension of IMpower133 ITT)
At 59.4-mo median follow-up, 3-/4-/5-year OS in atezolizumab+CE arm: 16% / 13% / 12%
Population: Extensive-stage small-cell lung cancer survivors from IMpower133 atezolizumab+carboplatin/etoposide arm enrolling in IMbrella A extension
RATIONALE-312
tislelizumab + etoposide + carboplatin or cisplatin vs placebo + etoposide + carboplatin or cisplatin
mOS 15.5 vs 13.5 mo (HR 0.75, 95% CI 0.61-0.93, one-sided P=0.0040); mPFS 4.7 vs 4.3 mo (HR 0.64, 95% CI 0.52-0.78, P<0.0001)
Population: Previously untreated extensive-stage small-cell lung cancer (Chinese population)
EXTENTORCH
toripalimab + etoposide + platinum (EP) vs placebo + etoposide + platinum (EP)
mOS 14.6 vs 13.3 mo (HR 0.80, 95% CI 0.65-0.98, P=0.03); PFS HR 0.67 (95% CI 0.54-0.82, P<0.001)
Population: Treatment-naive extensive-stage small-cell lung cancer (Chinese population)
LS-SCLC concurrent chemoradiotherapy
6
From Turrisi's 45 Gy BID to ADRIATIC's durvalumab consolidation — 25 years of LS-SCLC paradigm upgrade
TURRISI-1999-INT-0096
45 Gy twice daily over 3 weeks (BID) + cisplatin/etoposide vs 45 Gy once daily over 5 weeks (QD) + cisplatin/etoposide
mOS 23 mo (BID) vs 19 mo (QD), p=0.04; 2-yr OS 47% vs 41%; 5-yr OS 26% vs 16%; grade 3 esophagitis 27% vs 11% (p<0.001)
Population: Patients with limited small-cell lung cancer treated concurrently with cisplatin-etoposide x4 cycles
CONVERT
66 Gy in 33 once-daily fractions of 2 Gy over 45 days + cisplatin-etoposide vs 45 Gy in 30 twice-daily fractions of 1.5 Gy over 19 days + cisplatin-etoposide
mOS 30 mo (twice-daily) vs 25 mo (once-daily); HR 1.18 (95% CI 0.95-1.45, p=0.14); 2-yr OS 56% vs 51%; twice-daily remains standard of care
Population: Adults with cytologically or histologically confirmed limited-stage SCLC, ECOG 0-2
CALGB-30610-RTOG-0538
70 Gy once-daily thoracic radiotherapy + chemotherapy vs 45 Gy twice-daily thoracic radiotherapy + chemotherapy
mOS 30.1 mo (70-Gy QD) vs 28.5 mo (45-Gy BID); HR 0.94 (95% CI 0.76-1.17, P=0.594); 5-yr OS 32% vs 29%; 45-Gy BID remains standard
Population: Patients with limited-stage small-cell lung cancer receiving concurrent chemoradiotherapy
ADRIATIC
durvalumab 1500 mg q4w consolidation for up to 24 months vs placebo q4w
mOS 55.9 vs 33.4 mo (HR 0.73, 98.321% CI 0.54-0.98, P=0.01); mPFS 16.6 vs 9.2 mo (HR 0.76, 97.195% CI 0.59-0.98, P=0.02)
Population: Limited-stage SCLC without progression after concurrent platinum-based chemoradiotherapy
YU-2024-HYPERFRAC
VMAT 54 Gy in 30 fractions (twice-daily, simultaneous integrated boost) + platinum/etoposide vs VMAT 45 Gy in 30 fractions (twice-daily) + platinum/etoposide
mOS 60.7 mo (54 Gy) vs 39.5 mo (45 Gy); HR 0.55 (95% CI 0.37-0.72, p=0.003); grade 3-4 esophagitis 13% vs 12% (p=0.84); trial terminated early for clinical benefit
Population: LS-SCLC patients age 18-70, ECOG 0-1, enrolled at 16 Chinese public hospitals Jun 2017 - Apr 2021
NRG-LU005
Concurrent chemoradiation + atezolizumab 1200 mg q3w concurrent and adjuvant (up to 17 cycles) vs Concurrent chemoradiation alone (platinum/etoposide + 66 Gy QD or 45 Gy BID)
mOS 31.1 mo (CRT+atezo) vs 36.1 mo (CRT alone); HR 1.03 (95% CI 0.80-1.32); mPFS 12.1 vs 11.4 mo; no OS benefit from adding atezolizumab
Population: Limited-stage SCLC, stage Tx-IV, N0-3, M0, ECOG PS 0-2, after 1 induction chemo cycle
Prophylactic cranial irradiation (PCI)
4
Evolution of brain protection: from whole-brain 25 Gy to hippocampal-avoidance IMRT
SLOTMAN-PCI-2007
Prophylactic cranial irradiation (PCI) vs No further therapy (observation)
1-yr risk of symptomatic brain metastases 14.6% vs 40.4% (HR 0.27, 95% CI 0.16-0.44, P<0.001); mOS 6.7 vs 5.4 mo; 1-yr OS 27.1% vs 13.3%
Population: Patients age 18-75 with extensive-stage SCLC who responded to chemotherapy
PCI99-01
Higher-dose PCI 36 Gy (18 fx of 2 Gy QD, or 24 fx of 1.5 Gy BID) vs Standard-dose PCI 25 Gy in 10 daily fractions of 2.5 Gy
2-yr brain mets 29% (25 Gy) vs 23% (36 Gy), HR 0.80 (95% CI 0.57-1.11, p=0.18, NS); 2-yr OS 42% vs 37%, HR 1.20 (95% CI 1.00-1.44, p=0.05) favoring 25 Gy; 25 Gy remains standard
Population: Limited-stage SCLC in complete remission after chemotherapy and thoracic radiotherapy
CREST
Thoracic radiotherapy 30 Gy in 10 fractions + PCI, after chemotherapy response vs No thoracic radiotherapy, PCI only, after chemotherapy response
1-yr OS 33% (TRT) vs 28% (control), HR 0.84 (95% CI 0.69-1.01, p=0.066, not significant); 2-yr OS 13% vs 3% (p=0.004); PFS HR 0.73 (p=0.001)
Population: Extensive-stage SCLC, WHO PS 0-2, responded to chemotherapy
RTOG-0212-HIPPO
Hippocampus-avoidance PCI (HA-PCI) 25 Gy in 10 fractions vs Standard PCI 25 Gy in 10 fractions
HVLT-R total recall decline >=5 pts at 4 mo: 29% (PCI) vs 28% (HA-PCI), p=1.000 (NS); OS not different (p=0.43); 2-yr brain mets 20% (PCI) vs 16% (HA-PCI)
Population: SCLC patients receiving PCI (70% limited-stage in both arms), enrolled Apr 2013 - Mar 2018
Second-line and beyond
5
From topotecan monotherapy to DLL3 BiTE tarlatamab — the first truly new mechanism in 50 years
TOPOTECAN-ORIGINAL-PHASE2
Topotecan 1.5 mg/m2 daily x5 q21d vs Cyclophosphamide 1000 mg/m2 + doxorubicin 45 mg/m2 + vincristine 2 mg (CAV), day 1 q21d
ORR 24.3% (topotecan) vs 18.3% (CAV), P=0.285; mTTP 13.3 vs 12.3 wks (P=0.552); mOS 25.0 vs 24.7 wks (P=0.795); topotecan improved symptom control in 4/8 symptoms
Population: SCLC patients who relapsed >=60 days after completion of first-line therapy (sensitive relapse), ECOG <=2
OBRIEN-TOPOTECAN-2006
oral topotecan 2.3 mg/m^2/d days 1-5 q21d + best supportive care vs best supportive care alone
Median OS 25.9 vs 13.9 weeks (log-rank P=0.0104); ORR 7% PR + 44% SD; grade 4 neutropenia 33% on topotecan
Population: Relapsed small-cell lung cancer not candidates for standard IV therapy
CHECKMATE-032
nivolumab monotherapy or nivolumab + ipilimumab (various doses) vs no control (single-arm cohorts)
ORR: nivo3 10% (10/98); nivo1+ipi3 23% (14/61); nivo3+ipi1 19% (10/54); durable responses observed
Population: Recurrent/progressive small-cell lung cancer after prior chemotherapy
KEYNOTE-028-158
pembrolizumab monotherapy (10 mg/kg q2w or 200 mg q3w) vs no control (single-arm pooled)
ORR 19.3% (95% CI 11.4-29.4); 2 CR + 14 PR; 61% of responders had DOR ≥18 mo
Population: Recurrent or metastatic SCLC previously treated with ≥2 lines of therapy
DELLPHI-301
tarlatamab (DLL3 × CD3 BiTE) 10 mg or 100 mg IV q2w vs no control (single-agent dose comparison)
ORR 40% (10-mg) vs 32% (100-mg); mPFS 4.9 vs 3.9 mo; 9-mo OS 68% vs 66%; CRS in 51-61%
Population: Previously treated advanced small-cell lung cancer (median 2 prior lines)
Maintenance / combination exploration
4
Extending PFS after 1L IO: PD-L1 + anti-angiogenic / PARP / DLL3 combinations in exploration
TREASURE
Atezolizumab maintenance + thoracic radiotherapy (TRT) vs Atezolizumab maintenance alone
Protocol only — primary endpoint OS; safety interim planned after 23 TRT patients; trial later terminated for toxicity (not reported in this paper)
Population: Extensive-disease SCLC with any response to standard induction chemo-immunotherapy
DURABLE
durvalumab + anlotinib maintenance vs durvalumab maintenance
Protocol publication only — primary efficacy results not yet indexed on PubMed (results presented at conference)
Population: Extensive-stage small-cell lung cancer without progression after four cycles platinum chemotherapy + durvalumab
DELLPHI-303
tarlatamab + atezolizumab or durvalumab as maintenance after first-line chemo-immunotherapy vs no control (single-arm)
mOS 25.3 mo (95% CI 20.3-NE) from start of maintenance; CRS 24% serious; manageable safety; phase 3 NCT06211036 ongoing
Population: Extensive-stage small-cell lung cancer without progression after first-line chemo-immunotherapy
MATCH-TRIAL-SCLC
Cisplatin/carboplatin + etoposide + atezolizumab 1200 mg + concurrent LDRT 15 Gy/5 fx (3 Gy/fx) x4 cycles, then atezolizumab maintenance vs None (single-arm)
Confirmed ORR 87.5% (95% CI 75.9-94.8); mPFS 6.9 mo (95% CI 5.4-9.3); mOS 16.9 mo (95% CI 14.0-32.9); 3-yr OS 35.1%; deep responders (>70.2% depth) 3-yr OS 57.4% vs 18.8% (HR 0.28)
Population: Treatment-naive extensive-stage SCLC, enrolled Dec 2020 - Mar 2022 across Chinese multicenter sites
Historical chemo / supportive care
3
From CAV to PE to EL — standard chemotherapy evolution + myeloprotection
NIELL-2002-INTERGROUP
Paclitaxel 175 mg/m2 + etoposide 80 mg/m2 d1-3 + cisplatin 80 mg/m2 + G-CSF (PET) x6 cycles vs Cisplatin 80 mg/m2 + etoposide 80 mg/m2 d1-3 (EP) x6 cycles q3w
mOS 10.6 mo (PET) vs 9.9 mo (EP), P=0.169 (NS); median failure-free survival 6 vs 5.9 mo (P=0.179); toxic deaths 6.5% vs 2.4%; PET did not improve outcomes
Population: Untreated extensive-stage small-cell lung cancer
EL-PHASE3-CHINA
Lobaplatin 30 mg/m2 d1 + etoposide 100 mg/m2 d1-3 q21d (EL) vs Cisplatin 80 mg/m2 d1 + etoposide 100 mg/m2 d1-3 q21d (EP)
mPFS 5.1 vs 5.3 mo (P=0.786); mOS 10.6 vs 9.7 mo (P=0.701); DCR 85.5% vs 86.7% (P=0.848); EL had lower nephrotoxicity (2.5% vs 11.7%, P=0.008) and GI toxicity
Population: Previously untreated extensive-stage SCLC, enrolled at 17 sites in China Sep 2010 - May 2013
TRACES
trilaciclib prior to etoposide + carboplatin vs placebo prior to etoposide + carboplatin
Cycle 1 DSN 0 vs 2 days (P=0.0003); mOS 12.0 vs 8.8 mo (HR 0.69, 95% CI 0.40-1.22); mPFS 4.8 vs 4.3 mo (HR 0.86, 95% CI 0.53-1.39)
Population: Chinese extensive-stage small-cell lung cancer receiving first-line chemotherapy (myeloprotection focus)