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
Large subset of acquired resistance remains undefined by genomic analysis. Important proteomic work included on this trial identifies alterations in AXL and MET at progression. #ESMO22
Outcomes with osimertinib as expected. Takeaways from ELIOS include the difficulties in getting paired biopsies at progression for analysis and the frequency of acquired MET amp and EGFR C797S at progression on 1L osimertinib. Await more data including histology. #ESMO22
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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. 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
Dr. Baohui Han presents SUNRISE: randomized phase II study of sintilimab (PD1) and anlotinib (anti-angiogenic TKI) in metastatic NSCLC. #ESMO22
Study design here shows randomization to first-line sintilimab + anlotinib or chemo (with sintilimab at progression). Some concerns about randomization to chemotherapy without immunotherapy in a modern day study. #ESMO22
Baseline characteristics show a fairly high proportion of never smokers. SUNRISE excluded EGFR, ALK, and ROS1 - would like details on testing methods and presence of other drivers. More pts with brain and liver metastases in the sintilimab + anlotinib arm. #ESMO22