#ASCO20 Outcomes after potentially curable surgical resection still quite poor for #NSCLC.
#ASCO20 In the advanced setting, #EGFR TKI therapy is our clear standard. Relatively rapid implementation and the current SOC for stage IV NSCLC is osimertinib. #LCSM#OncoAlert
#ASCO20 The phase III #ADAURA trial included patients with resected stage IB, II or IIIA NSCLC (with or without adjuvant chemotherapy) with an #EGFR deletion 19 or L858R mutation. CNS imaging and post-op CT required before entry. #OncoAlert#LCSM
#ASCO20 Study design very straightforward with stratifiation by stage, mutation and race. Randomized to osimertinib 80mg qd vs placebo for 3 years (or progression). Stopped early by IDMC recommendation. Note: min f/u only 1 year, most had 2y of f/u. #OncoAlert#LCSM
#ASCO20 Baseline characteristics show about 55% of patients received adjuvant chemotherapy. 65% Asian, 70% non-smoker, 55% #EGFR del19. #OncoAlert#LCSM
#ASCO20 DFS for patients with stage II/IIIA (primary endpoint) HR 0.17! Only 33% mature but impressive landmark DFS rates: 90% with osimertinib at 2y vs 44% with placebo. Early separation of the curves, consistent with prior reports. Surgery often not curative in this setting.
#ASCO20 Forest plot for DFS shows impressive HR in every major subgroup, though IB has a large CI. HR for those who received adjuvant chemo was 0.18 and for those who did not 0.23 #OncoAlert#LCSM
#ASCO20#ADAURA DFS rate by stage showing improvement across the board, moreso in stage II (HR 0.17) and stage III (HR 0.12) than stage IB (HR 0.50). #OncoAlert#LCSM
#ASCO20 DFS KM curves by stage all show early separation, impressive HR. A reminder of how few patients with stage II and especially stage IIIA EGFR+ NSCLC we actually cure with surgery +/- chemotherapy. #OncoAlert#LCSM
#ASCO20 Very early and immature OS curves for #ADAURA. This will be the key. Note that this HR of 0.40 (95% CI 0.18, 0.90) is not statistically valid at this point of maturity. We will be watching this closely in the years to come (5% maturity). #OncoAlert#LCSM
#ASCO20 Safety summary here and critical for an adjuvant setting. Overall appears quite safe but our bar is higher in patients who may not have active disease and without a clear OS benefit yet. And this is not 4 cycles - this is 3 years. QOL is very important. #OncoAlert#LCSM
#ASCO20 Tornado plot illustrates osimertinib safety and while rate of G3+ AEs are quite low, 46% with all grade diarrhea is notable (again, 3y of therapy). #OncoAlert#LCSM
#ASCO20 Breakdown of future considerations for #ADAURA by @DrRoyHerbstYale - glad to see QOL and capture of subsequent therapies (how many in placebo receive osi at PD) and characterization of PD. Will also need to see how many crossover after unblinding... #OncoAlert#LCSM
#ASCO20 Overall, DFS HR of 0.21 across stages. 2y DFS rate 89% with osimertinib vs 53% with placebo. Immature, yes. Perfect dataset, no. But impressive nonetheless. #OncoAlert#LCSM
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Dr. @marinagarassino at #WCLC24 Presidential Plenary presents Normalized Membrane Ratio of TROP2 as a biomarker for datopotamab deruxtecan in TROPION-Lung01 (Dato-DXd vs docetaxel in previously treated NSCLC which previously showed PFS benefit with Dato-DXd.
#WCLC24 TROP2 IHC has been a poor predictive marker. Normalized Membrane Ratio (NMR) factors in receptor internalization. Ratio is membrane expression over membrane plus cytoplasmic expression (using optical density from digitized slide) and lower would be more favorable.
#WCLC24 TROP2 QCS-NMR seems to be a much better predictor of benefit with datopotamab deruxtecan in BEP and in non-sq non-AGA subset: in NMR+, PFS HR 0.57 and KM shows clear separation.
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