Important Studies: Extensive Stage

Question 1

Thoracic RT after PCI?

Answer 1

CREST (Slotman et al, Lancet, 2015, Slotman et al, Lancet, 2015): ES-SCLC who responsed to chemo, ECOG 0-2→ 30 Gy thoracic RT + PCI vs. →PCI.
2-yr OS 13% vs. 3%
1-yr OS trend to improvement 33% vs. 28%, p=0.066
6-mo PFS 24% vs. 7%
Thoracic progression 44% vs. 80%
CR only 5% in both arms
From Slotman’s author’s reply:
Benefit was only in those with residual disease present. 89% had residual disease. If residual disease on CT:
1-yr OS 33% vs. 26%
2-yr 12% vs. 2%
Thoracic progression 44% vs. 83%
Consolidative thoracic RT improves OS in extensive stage SCLC that responded to chemo. However the primary endpoint of 1-yr OS was not met.

Question 2

Thoracic RT?

Answer 2

University Hospital Kragujevac, Yugoslavia (Jeremic et al, JCO, 1999): Cis/etop x3 then if distant CR and local CR/PR: →thoracic RT 54 Gy/36 fx BID + cis/etop x2 vs.
→cis/etoposode x4 Followed by PCI. Improved OS and LRR with thoracic RT. 5-yr OS 9% vs. 4 %. 5-yr LRR-free 20% thoracic RT vs. 8%.

Question 3

Consolidative RT to distant sites?

Answer 3

NRG/RTOG 0937 (Gore et al, ASTRO, 2016): 1-4 metastatic lesions and no brain metastases after CR/PR from 4-6 cycles platinum chemo. “Phase II: →PCI 25 Gy only vs. →PCI and consolidative RT to thorax and original sites of mets. Closed early due to futility
1-yr OS unchanged 60% vs. 51% consolidatived RT, p=0.21

Question 4

Prophylactic cranial irradiation?

Answer 4

EORTC 08993/22993 (Slotman et al, NEJM, 2007): “4-6 cycles of chemo, wait 4-6 weeks, then if any response to therap→ PCI 20-30 Gy vs. observation. 1-yr OS 27% vs. 13. PCI reduces symptomatic brain mets and improves DFS and OS. This trial was performed prior to the MRI era.

National Kyushu Cancer Center, Fukuoka, Japan (Takahashi et al, Lancet Oncol, 2017): Extensive stage SCLC who responded to platinum chemotherapy. No brain metastases on MRI. →PCI 25 Gy/10 fx vs. observation. PCI did not improve OS in extensive stage SCLC staged with MRI. LC was improved.

Question 5

Immunotherapy?

Answer 5

IMpower133 (Horn et al, NEJM, 2018): Extensive stage SCLC with no prior therapy. →atezolizumab (anti PD-L1) + carbo/etopvs. →placebo + carbo/etop.
Median OS 12.3 mos vs. 10.3 mos
Median PFS 5.2 mos vs. 4.3 mos
First line atezolizumab in extensive stage SCLC improves OS and PFS