#ESMO20 Practice changing data presented by Dr. Cecile Le Pechoux @GustaveRoussy. The prospective, randomized phase III LUNG-ART study explores the benefit of post-operative radiotherapy for completely resected #NSCLC: no OS benefit seen. #LCSM@OncoAlert
#ESMO20 Post-operative radiotherapy found to be detrimental after resection for pN0 and pN1 NSCLC but unclear role in pN2. Data supporting its benefit but lack of prospective studies. Had been standard for many in pN2 (including myself). #LCSM@OncoAlert
#ESMO20 The LUNG ART phase III trial (IFCT-0503) enrolled patients with completely resected N2 NSCLC and randomized 1:1 to 3D conformal post operative radiotherapy (54 Gy over 5.5 weeks). Median follow up nearly 5 years. #LCSM@OncoAlert
#ESMO20 This was a fairly rigorous trial. 96% of patients received adjuvant chemotherapy, over 90% were staged with PET. All had N2 involvement and 40% were microscopic, unforeseen N2 (reminder of how important mediastinal staging is). #LCSM@OncoAlert
#ESMO20 Mostly lobectomy (10-12% pneumonectomy), 89% 3DRT, median lung V20 was 23%. #LCSM@OncoAlert
#ESMO20 Primary endpoint here. No significant difference in PFS. 3y PFS rate 43.8% in control and 47.1% with PORT, median 22.8m vs 30.5m (HR 0.85, p=0.16). #LCSM@OncoAlert
#ESMO20 When we look at DFS, control arm much more likely to suffer mediastinal relapse (46.1% vs 25%) but death more common in the PORT arm (14.6% vs 5.3%). #LCSM@OncoAlert
#ESMO20 LUNG ART showed PORT did not impact survival. The 3y OS rate was 66.5% with PORT and 68.5% without PORT. Causes of death differed: in the control arm, 86.1% of deaths due to recurrence vs 69.4% with PORT but cardio-pulmonary deaths in 16.2% of PORT vs. 2% in control #LCSM
#ESMO20 LUNG ART showed no improvement in DFS or OS with post-operative radiotherapy for completely resected N2 NSCLC. In fact, PORT had a non-significant increase in DFS and increased cardiopulmonary toxicity. Routine PORT no longer SOC. #LCSM@OncoAlert
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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