Dr. Idris Bahce presents data from the INCREASE trial - ipilimumab plus nivolumab and chemoradiation followed by surgery in resectable and borderline resectable NSCLC. #ESMO22
Focus is on high T stage and low N stage - not resectable initially but potentially resectable after therapy. Patients here received nivo/ipi on day 1 and nivo on day 22 with chemoradiation then resection 6w later (after restaging) with pCR/MPR primary endpoint. #ESMO22
#ESMO22 Patient disposition here - of 26 patients who completed induction therapy, 3 are still on therapy and 24 completed surgery. Included 66% T4 and 59% N0 (only 13% N2). Majority (63%) had PDL1 high disease. There was one G5 AE (COVID). No AE prevented surgery.
Wow. Of those who underwent surgery after neoadjuvant nivo + ipi + radiation, 63% (!) had pCR and 79% had MPR. #ESMO22
Radiographic response rate only 15% - reinforcing disconnect between RECIST and pathologic responses. Illustrative superior sulcus case. Some interesting changes in CD8+ subset of T cells especially in those who have a pCR #ESMO22
Small study but impressive pCR rate here. Appealing for superior sulcus tumors, where chemoradiation is our standard, but perhaps we need to revisit the role of neoadjuvant radiation in resectable NSCLC in the perioperative immunotherapy era? #ESMO22
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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
Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) targeting #HER2 and in DESTINY-Lung01, RR was encouraging at 55% but some concern for toxicity (adjudicated drug-related ILD in 26% of cases). #ESMO22
In DESTINY-Lung02, we have a randomization of pts with #HER2 mt NSCLC (with prior therapy) to the 6.4 mg/kg dose used in DESTINY-Lung01 or a lower, 5.4 mg/kg dose. RR higher at 5.4 (due to maintained intensity from less tox? or imbalance in baseline characteristics?) #ESMO22
Dr. Koichi Goto starts the lung mini oral session with results from DESTINY-Lung02 of the recently approved trastuzumab deruxtecan in #HER2 NSCLC #ESMO22
DESTINY-Lung02 compared two doses of trastuzumab deruxtecan (T-DXd) in #HER2 previously treated NSCLC (5.4 mg/kg vs 6.4 mg/kg): RR 58% and DoR 8.7m at the lower dose compared to 43% at 6.4 mg/kg. #ESMO22
Importantly- interstitial lung disease much less frequent at the 5.4 mg/kg dose (5.9%, only 1 case of G3). This is the FDA approved dose of trastuzumab deruxtecan in #HER2 NSCLC #ESMO22
Discussant Dr. @NReguart reminds us of the heterogeneity of stage III NSCLC and our teaching has been to determine resectability before treatment. The INCREASE study starts to challenge that. #ESMO22
The difference here is radiation and in T3/T4 NSCLC, local control is so critical. Largely unexplored to date. The INCREASE study explores quad-modality therapy and the results were quite impressive. High pCR rates and seen across PDL1 strata, not just in PDL1 high. #ESMO22
#ESMO22 High G3 TRAE rates but note that use of platinum + etoposide was common and many of these may have been paper toxicities. Any grade pneumonitis only 11% (note radiation dose was usually 50 Gy).