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Wei Nie
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OA07 - Immuno-biology and Novel Immunotherapeutics from Bench to Bed (ID 228)
- Event: WCLC 2020
- Type: Oral
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 2
- Moderators:
- Coordinates: 1/30/2021, 10:30 - 11:30, Scientific Program Auditorium
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OA07.03 - Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients (ID 944)
10:30 - 11:30 | Presenting Author(s): Wei Nie
- Abstract
- Presentation
Introduction
Comutations in DNA damage response and repair (DDR) pathways have been reported to be potential predictors for immune checkpoint inhibitors (ICIs) treatment. However, this statement has not been confirmed yet. In this study, we aimed to explore the predictive value of comutations in DDR pathways using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in non-small cell lung cancer (NSCLC) patients receiving atezolizumab or docetaxel.
Methods
Clinico-pathological data of NSCLC patients from POPLAR and OAK trials were collected. Blood-based FoundationOne NGS assay was used to determine genetic alterations and blood tumor mutational burden (bTMB). Nonsense mutations and splice site alterations of DDR genes were considered deleterious. The deleterious status of missense mutations was determined by manual review in COSMIC and OncoKB databases. Comutations (co-mut+) were defined as deleterious alterations in two or more DDR pathways or deleterious alteration(s) in one DDR pathway plus missense mutation(s) of unknown significance in other DDR pathways. Overall survival (OS), progression-free survival (PFS), and durable clinical benefit (DCB) were compared between co-mut+ patients than co-mut- patients receiving atezolizumab or docetaxel.
Results
A total of 853 NSCLC patients were included (n=429 for atezolizumab and n=424 for docetaxel) in this study. Of them, 49 patients (5.7%) were classified as co-mut+ in the whole cohort. The baseline characteristics were comparable between co-mut+ and co-mut- patients in terms of age, race, gender, histology, smoking status, lines of treatment, EOCG PS, and PD-L1 expression. Patients with co-mut+ had significantly longer sum of the diameters of tumor (P=0.006), number of metastatic site (P=0.026), and increased median bTMB (20 vs. 7 mutations/Mb, P<0.001) than those with co-mut-. A significantly higher DCB was observed in co-mut+ patients than co-mut- patients receiving atezolizumab (56.7% vs. 30.6%, P=0.003). Among co-mut+ patients, atezolizumab significantly improved median OS (15.5 months vs. 6.2 months; adjusted hazard ratio [HR] for death, 0.299; 95% CI, 0.154 to 0.578; P=0.008) and median PFS (6.9 months vs. 3.3 months; adjusted HR for disease progression or death, 0.395; 95% CI, 0.209 to 0.747; P=0.004) compared with docetaxel. Importantly, the interaction between co-mut+ and treatment was significant for OS (interaction P=0.014) and PFS (interaction P=0.010).
Conclusion
Comutations in DDR pathways were significantly associated with higher response rate to atezolizumab and improved survival in NSCLC patients. The presence of comutations in DDR pathways could help to identify patients who will benefit from ICIs therapy.
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OA07.09 - Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints (ID 1480)
10:30 - 11:30 | Author(s): Wei Nie
- Abstract
- Presentation
Introduction
Evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic TKIs in treatment naïve advanced NSCLC patients is insufficient. Our phase I study (NCT03628521) of sintilimab (anti-PD-1) combined with anlotinib (multi-target anti-angiogenesis TKI) had showed encouraging overall response as first line therapy for advanced NSCLC regardless of PD-L1 expressions. Here we present the updated efficacy and safety results and more sub-group analyses.
Methods
Eligible patients were treatment-naive, stage IIIB/IV NSCLC patients without EGFR/ALK/ROS1 mutations. Participants were given sintilimab (200mg IV day1 q3w) and anlotinib (12mg QD day1-14 q3w) till disease progression or unacceptable toxicity. The primary endpoints were ORR and safety, and the secondary endpoints included DCR, PFS and OS.
Results
From Sept. 2018 to Feb. 2019, 22 patients were enrolled and treated. As of Apr. 30th 2020, median follow-up was 15.8 months (range, 8.3-19.3), median treatment duration was 14.6 months (range, 3.7-19.3). In total, 16 patients achieved confirmed PR, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). Patients with adenocarcinoma (n=9) seemed to have better response than squamous cell type (n=12, 88.9% vs 58.3%). The median TTR was 1.6 months (95% CI, 1.4, 2.9) and the median DOR was NR (95% CI: 3.2m, NC). The median PFS was 15 months (95% CI, 8.3 months-NR), and the 12-month PFS rate was 71.4% (95% CI, 47.2%, 86.0%). Patients with squamous cell carcinoma had similar 12m PFS rate with adenocarcinoma (77.8% vs 66.7%). 12m PFS rate was consistent across different biomarker status. OS data was immature and the estimated 12-month OS rate was 95.5% (95% CI, 71.9%, 99.3%). With more follow-up, grade ≥3 TRAE occurred in 54.4% patients, and grade ≥3 irAE was 4.5%. The most common irAE were hypothyroidism (50%), pneumonitis (13.6%), myositis (4.5%) and adrenal insufficiency (4.5%). Five patients required dose reduction of anlotinib and one patient had treatment discontinuation due to grade 3 rash.
ConclusionITT
（n=22）
PD-L1+
（n=13）
PD-L1 -
（n=8）
TMB ≥ 10
（n=6）
TMB ＜ 10
（n=10）
median PFS, m
(95% CI）
15
(8.3, NR)
NR
(7.7, NR)
14
(4.5, 15)
NR
(NR, NR)
14
(4.3, 15)
12 month PFS rate
(95% CI)
71.4%
(47.2%, 86.0%)
76.9%
(44.2%, 91.9%)
62.5%
(22.9%, 86.1%)
100%
(100%, 100%)
60.0%
(25.3%, 82.7%)
With longer follow-up, combination of sintilimab and anlotinib demonstrated durable efficacy and good tolerability. To our knowledge, this is the first study that assessed a PD-1 inhibitor plus an anti-angiogenesis TKI in first-line setting of advanced NSCLC. A phase II randomized trial (NCT04124731) is currently ongoing to further investigate this new chemo-free strategy.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.11 - Anlotinib Versus Chemotherapy as a Third-Line or Further Treatment for Advanced Small Cell Lung Cancer (ID 675)
00:00 - 00:00 | Author(s): Wei Nie
- Abstract
Introduction
The optimal third-line or further treatment for advanced small cell lung cancer (SCLC) remains unclear.Anlotinib,which is a novel multitarget tyrosine kinase inhibitor,could inhibit tumor angiogenesis and proliferative signaling.Therefore,this retrospective study aimed to compare the efficacy and safety of anlotinib versus chemotherapy of patients with advanced SCLC progressing after second-line or further treatment.
Methods
This study included 55 advanced SCLC patients (n=28 for anlotinib group and n=27 for chemotherapy group) from Shanghai Chest hospital between January 2017 and September 2019.Detailed demographic,survival data,and safety data were collected.Kaplan-Meier method and log-rank test were used to assess median progression-free survival (PFS) and overall survival (OS) with 95% confidence intervals (CIs).
Results
PFS was significantly longer in the anlotinib group [median PFS 3.58 versus 2.56 months;hazard ratio (HR)=0.42,95% CI:0.24-0.75,P=0.003] than that in the chemotherapy group.Although anlotinib did not improve OS (median OS 5.32 versus 6.57 months;HR=1.21,95% CI:0.60-2.46,P=0.592),non-smokers derived more survival benefit from anlotinib than ever/current smokers (Pinteraction for OS=0.04).In addition,similar result was found for PFS (Pinteraction for PFS=0.08).Considerable improvement in disease control rate was observed in the anlotinib group over the chemotherapy group.Four (14.3%) patients in the anlotinib group versus five (18.5%) patients in the chemotherapy group had treatment-related grade 3-4 adverse events.
Conclusion
Anlotinib treatment resulted in an improvement of PFS versus chemotherapy in previously treated SCLC,with a favourable safety profile.Non-smoking seemed to be a predictive factor of anlotinib efficacy.Prospective studies were needed to confirm our findings.
