#ESMO20 Eagerly awaited presentation by @peters_solange on consolidation nivolumab and ipilimumab (vs observation) for patients with LS-SCLC after chemoradiation: ETOP/IFCT 4-12 STIMULI trial #LCSM@OncoAlert@myESMO
#ESMO20 While we have adopted IO for ES-SCLC, its role in LS-SCLC is not yet known, though outcomes in LS-SCLC are still poor. Nivo/ipi has activity in SCLC, but note that the consolidation/maintenance approach in ES-SCLC was not successful. #LCSM
#ESMO20 Study design outlined here: enrolled at diagnosis or after 1 dose of chemotherapy to allow referrals (smart design). Standard concurrent CRT followed by 1:1 IO vs observation. Used nivo 1mg/kg and ipi 3mg/kg q3w x 4 cycles with maintenance nivolumab (not low dose ipi).
#ESMO20 Statistical design including explanation of premature closure to accrual which led to a pretty long period of accrual. Treatment failure in observation was due to progression whereas in nivo/ipi arm, it was toxicity.
#ESMO20 Consolidation nivo/ipi after chemoradiation for LS-SCLC did NOT improve PFS. HR 1.02 with curves crossing multiple times. Median PFS for nivo/ipi was 10.7m versus 14.5m for observation. #LCSM@OncoAlert
#ESMO20 Subgroup analysis without clear trends to identify groups that would benefit from nivo/ipi consolidation. Patterns of progression similar, mostly new lesions. #LCSM@OncoAlert
#ESMO20 Consolidation nivo/ipi after concurrent chemoradiation for LS-SCLC did not improve survival with an OS HR 1.06. Interesting approach looking at piecewise hazard ratios and this may mature differently but as of now, no OS benefit. #LCSM
#ESMO20 Disappointing OS results with nivo/ipi consolidation. Subgroup analyses here not very telling. More toxicity with nivo/ipi, naturally, vs observation, but nothing unexpected. #LCSM
#ESMO20 Overall, the use of consolidation nivolumab and ipilimumab after concurrent chemoradiation for LS-SCLC did not improve PFS or OS. Longer follow up may inform late impact, though crossover at relapse may make that challenging. #LCSM@OncoAlert@myESMO
#ESMO20 My immediate reaction is disappointing as there is a lot of rationale for IO post CRT in LS-SCLC. Is it the ipi - is the dose too high in a population with co-morbidities (worsened by CRT)? Parallels to CheckMate 451 (maint nivo/ipi in ES-SCLC did not improve OS)? #LCSM
#ESMO20 This question of IO post CRT for LS-SCLC is still valid (better without CTLA4?). Consider referring to NRG-LU005 (chemoradiation +/- atezolizumab, NCT03811002) or ADRIATIC (chemoradiation followed by durva +/- treme, NCT03703297). #LCSM
Dr. Shun Lu presents interim results from the perioperative NEOTORCH study at the #ASCOPlenarySeries. Randomized pts with resectable stage II/III NSCLC to perioperative chemotherapy with toripalimab (anti-PD1) vs placebo. Another entry in the perioperative space? #LCSM
Includes resectable stage II/III (AJCC v8), EGFR/ALK wild type NSCLC. Pts receive 3 cycles of neoadjuvant chemotherapy + toripalimab vs placebo then surgery then 1 more cycle of adjuvant chemo (+tori/pbo) then 13 doses of maintenance toripalimab vs placebo. #ASCOPlenarySeries
First interim EFS analysis only for stage III. Includes 404 pts - but 926 screened. Would be interesting to see specific eligibility criteria not met in screening process. Reminder of how selected trial populations are and value of future real-world analyses. #ASCOPlenarySeries
Impressive data from #AEGEAN at #AACR23 from Dr. John Heymach and colleagues. This is the first of several phase III peri-operative IO studies in resectable NSCLC combining neoadjuvant chemo-immunotherapy followed by adjuvant immunotherapy.
Included stage IIA-IIIB (AJCC v8) with no EGFR/ALK & excluded pts who would require pneumonectomy. Large study with n=801 (CM816 was n=358). Pts received 4 cycles (not 3) of platinum-based chemo with durvalumab (anti-PDL1) or placebo, then surgery, then durvalumab / placebo x 1y.
Almost 75% received carboplatin over cisplatin. Global study; fairly even PDL1 distribution. 80% of pts went to surgery, 78% completed resection (90-95% of those were R0). Overall, 66% of pts began adjuvant phase (but 90% of those who had an R0 resection had adjuvant therapy).
There is a lot to consider in this first-line study of the #KRAS G12C inhibitor adagrasib plus pembrolizumab from #ESMOImmuno22. Some pleasant surprises in terms of safety. Definitely encouraging but need to see a bit more to be sold on this strategy. 🤔 #LCSM
We're looking for synergy with the two agents - more than an additive effect. Reason to believe there will be based on preclinical data showing the effect on T-cell infiltration from #KRAS inhibition. Similar to what has been shown with MEK inhibition. #ESMOImmuno22
The first-line dataset includes the phase Ib KRYSTAL-1 and the phase II KRYSTAL-7. In KRYSTAL-1 (n=7), 4/7 had a response and all were durable (>9m). G3 TRAEs in 4 pts (lipase elevation, LFTs, muscular pain, pneumothorax). #ESMOImmuno22
Dr. @ZPiotrowskaMD presents initial results from the ELIOS trial at #ESMO22 - molecular profiling of #EGFR mutant NSCLC after progression on 1L osimertinib.
In this study of highly motivated pts at esteemed sites, evaluable paired biopsy at PD only available in 46/115 pts (40%). Interestingly, 75 pts (65%) had paired biopsy but 27 failed NGS (23%). Speaks somewhat to the real world feasibility of a repeat biopsy approach. #ESMO22
Common co-mutations at baseline included TP53, EGFR amp, and CDKN2A loss. Acquired alterations included MET amp, EGFR C797S, ALK fusion, NKX2-1 amp. Mostly mutually exclusive. #ESMO22
Dr. Silvia Novello presents 5y update on KEYNOTE 407 (platinum plus tax and +/- pembrolizumab for 1L squamous NSCLC #ESMO22
With longer follow up, OS favors pembrolizumab arm with mOS 17.2 vs 11.6m (OS HR 0.71) in squamous NSCLC. 5y OS rate 18.4% vs 9.7%. PFS benefit (HR 0.62) and higher RR across PDL1 strata. #ESMO22
For patients who complete 2y of pembrolizumab, 3y OS rate (after completing 2y pembro) was 70% - though not all of those patients are cured (44% were alive without PD or subsequent therapy). #ESMO22
Dr. @marinagarassino presents 5-year efficacy and safety update of KEYNOTE-189 (1L carboplatin plus pemetrexed +- pembrolizumab in non-squamous NSCLC) #ESMO22
KEYNOTE 189 is our SOC and has shown a consistent benefit including improving OS even with a crossover rate of 57%. #ESMO22
KEYNOTE 189 shows sustained OS benefit with longer follow up and a 5y OS rate of 18.4% with an OS HR of 0.60. Better PFS and OS also observed. Benefit across PDL1 strata. No new safety signals . #ESMO22