ASCO 2020: SCLC (小細胞肺癌のまとめ)

Stephen V Liu, MD @StephenVLiu

#ASCO20 Cross trial comparisons are not valid! So don't look at this figure with all 4 OS KM curves from the 3 randomized phase III #SCLC chemo-IO trials: IMpower 133 (atezolizumab), CAPIAN (durvalumab, durvalumab + tremelimumab) and KEYNOTE 604 (pembrolizumab). #OncoAlert #LCSM pic.twitter.com/fzPIXfBSAI

拡大

Anna Farago, MD, PhD @AnnaFaragoMD

Beautiful discussions of ES-SCLC oral abstracts and posters by @teekayowo & @LaurenByersMD. Take-home messages: 1. 1st line chemo + PD(L)1 inhibition provides modest but consistent OS benefit across studies; 2. CTLA-4 adds toxicity without improving efficacy... #ASCO20 #SCLC 1/2 pic.twitter.com/fbLXpzCLnb

拡大

拡大

拡大

Anna Farago, MD, PhD @AnnaFaragoMD

3. Biomarkers are needed for defining & selecting SCLC subpopulations. PD-L1 and TMB won’t suffice. More hope for transcription factor subsets, MYC subsets. NEXT STEP prospective biomarker-driven studies with tumor biopsies. @charlesrudin @StephenVLiu @TGOliver2 @christine_lovly pic.twitter.com/JPwRRKDFMc

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Well balanced review of the #SCLC IO oral abstracts by @teekayowo. Clear and consistent benefit with addition of PD(L)1 therapy to front line chemotherapy with 2y OS rates ~ 22% across studies (prior analyses suggest 2y OS rate ~ 7% with chemo alone). #OncoAlert #LCSM pic.twitter.com/TSjNjZikS4

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Looking at the OS curves, later separation leads some to question value of concurrent IO. @teekayowo cautions against this interpretation, as do I. See CM451 where maintenance IO did not impact OS. Concurrent chemo-IO was the only effective approach. #OncoAlert pic.twitter.com/awNLRUlcNr

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Nivolumab + chemotherapy performed well in EA5161 (@LealTiciana) but a phase II is insufficient to change practice in the current environment. Going forward, similar trials are not justified without plans for confirmatory trials. #LCSM #OncoAlert pic.twitter.com/NKMk3fVhZZ

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 CASPIAN with more follow up confirms benefit of durvalumab but tremelimumab did not improve outcomes and treatment related deaths were 2x as high. Without a defined biomarker, @teekayowo declares further CTLA4 investigation in this setting unwarranted. Agreed. #LCSM pic.twitter.com/BLBkCiB8LS

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 KEYNOTE 604 did not meet its predefined threshold for OS improvement and has no immediate impact on practice. @teekayowo offers the design as a cautionary tale that sometimes, an uncomplicated study and analytic design is best. Wise words indeed. #OncoAlert #LCSM pic.twitter.com/Y1lF3DGcxu

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 The path forward is biomarkers. PDL1 and TMB were low lying fruit and are not enough to help guide treatment here. Other ongoing efforts are the key to enrich trials properly and deliver the types of benefit we need! pic.twitter.com/K3RLbcSPVo

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Long awaited results from KEYNOTE-604 by @charlesrudin. Randomized phase III trial for patients with treatment naive #SCLC. 453 patients randomized to 4 cycles of platinum/etoposide with either pembrolizumab or placebo. PCI optional, both arms. No TRT. #OncoAlert @IASLC pic.twitter.com/NMm98uURXE

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Co-primary endpoints of PFS and OS. Safety as expected - primarily hematologic adverse events, common with platinum/etoposide chemotherapy. Immune mediated adverse events usually low grade (thyroid, etc). #OncoAlert pic.twitter.com/pfroKb2gCx

拡大

拡大

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Addition of pembrolizumab to EP improved PFS (HR 0.73). Numeric improvement in median OS (9.7m to 10.8m) and 1y OS rate (45% from 40%) but did not cross superiority threshold for improvement in survival (OS HR 0.80). #OncoAlert pic.twitter.com/5JkF9GhRlK

拡大

拡大

Benjamin Besse @BenjaminBesseMD

CT-IO in SCLC — KN604 — OS curves : ~copy/paste of other studies, these (now familiar) shapes suggest only 10% of pts really derive an IO benefit. How to select pt? Our @EORTC REACTION ph2 randomized only chemosensitive pts after 2xEP. Enrollment completed! @teekayowo #ASCO20 pic.twitter.com/NXdQp0B5h4

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Update on CASPIAN by Luis Paz-Ares with first report on the durvalumab + tremelimumab arm and update on the durva arm. This was an open label phase III comparing platinum/etoposide vs chemo with durva alone vs chemo with durva and treme in 1L #SCLC. #OncoAlert @IASLC pic.twitter.com/O82dsw1CQu

拡大

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Durva/treme arm with slightly more CNS metastases. PCI only permitted on EP arm though some on D+T arm did receive it. While cisplatin or carboplatin permitted, vast majority received carbo (as expected). #OncoAlert #LCSM pic.twitter.com/CfzSF53gno

拡大

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Addition of durvalumab and tremelimumab to EP chemotherapy in #SCLC did not lead to a statistically significant improvement in OS. Median 10.4 vs 10.5 with chemotherapy, OS HR 0.82. There was a numeric increase in 2y OS rate (14.4% vs 23.4%). #OncoAlert #LCSM pic.twitter.com/EDbc1kPO01

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Subgroup analysis, PFS, and duration of response for the durvalumab + tremelimumab arm show interesting trends but overall, this combination did not meet its OS endpoint (unlike durvalumab or atezolizumab alone). #OncoAlert pic.twitter.com/fAzsAggyu4

拡大

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 Update on the durvalumab arm also provided with 11m more follow up and the OS benefit is maintained. Median OS 12.9 with durva/EP vs 10.5 with EP alone (HR 0.75), 1y OS rate 52.8% vs 39.3%, consistent with earlier report (HR 0.73, 1y 53.7% vs 39.8%). #OncoAlert pic.twitter.com/7FuG6oERIl

拡大

Stephen V Liu, MD @StephenVLiu

#ASCO20 CASPIAN OS results for all three arms on one KM curve. At 2y, durva/treme and durva seem to overlap but earlier, treme quite a bit lower. Could it be the higher toxicity rate (AEs leading to d/c 21.4% vs 10% with durva and 9% with chemo)? #OncoAlert #LCSM @IASLC pic.twitter.com/w1gg8bu604

拡大

拡大

拡大