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Jun Zhao
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Now Available
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.10 - Efficacy and Safety of Neoadjuvant PD-1 Blockade with Sintilimab in Resectable Non-Small Cell Lung Cancer (Now Available) (ID 3424)
07:00 - 11:15 | Author(s): Jun Zhao
- Abstract
- Presentation
Abstract
Background
NSCLC patients who have potentially resectable disease often subsequently relapse after surgery. New therapy that prevents relapse after surgery is desperately needed. In this study, we tested the efficacy and safety of neoadjuvant sintilimab, an anti-PD-1 antibody, for patients with resectable sqNSCLC in China.
Methods
All patients had treatment-naïve resectable sqNSCLC (stage IB-IIIA) that was confirmed by histopathology. Patients received two cycles of sintilimab (200 mg IV) on Day 1 and 22. Surgery was performed between Day 29-43. An enhanced PET/CT was obtained at baseline and seven days prior to surgery. Preliminary analysis of safety profile and efficacy was planned after at least 20 patients had received operation.
Results
As of Jan. 28, 2019, 22 patients (20 males and 2 females) with sqNSCLC received two doses of sintilimab followed by radical resection. The median age was 61.5 yr (range, 48 to 70). Six (27.3%) and four (18.2%) patients experienced neoadjuvant treatment emergent adverse events (TEAEs) and neoadjuvant treatment-related AEs (TRAEs), respectively. Most of the TEAEs and TRAEs were grade 1 or 2. Three patients achieved radiological partial response: an ORR of 13.6% based on RECIST 1.1. Ten patients (45.5%) achieved a major pathologic response (MPR, ≤10% viable tumor cells), including four (18.2%) had complete pathologic response (no viable tumor cell). There was a direct correlation between pathological response and decrease in the standardized uptake values (SUV) in the primary tumor. Among nine patients with > 30% decrease of SUV, eight had MPR, compared with no MRP response in the 11 patients with ≤30% decrease of SUV.
Conclusion
Neoadjuvant sintilimab for sqNSCLC patients was tolerable and the 45.5% MRP rate is encouraging. A decrease in SUV may be predictive of pathologic response after PD-1 therapy in sqNSCLC.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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OA04 - Immuno Combinations and the Role of TMB (ID 126)
- Event: WCLC 2019
- Type: Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Solange Peters, Martin Reck
- Coordinates: 9/08/2019, 15:15 - 16:45, Copenhagen (1980)
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OA04.03 - A Randomized Phase 3 Study of Camrelizumab plus Chemotherapy as 1<sup>st</sup> Line Therapy for Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (Now Available) (ID 1682)
15:15 - 16:45 | Author(s): Jun Zhao
- Abstract
- Presentation
Background
Platinum-based chemotherapy remains 1st line therapy for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers in China. Camrelizumab (SHR-1210, a potent anti‒PD-1 monoclonal antibody) has shown promising activity in multiple malignancies. Here, we report interim analysis results on efficacy and safety of camrelizumab plus carboplatin/pemetrexed as 1st line treatment in Chinese advanced/metastatic non-squamous NSCLC patients with negative oncogenic drivers.
Method
In this open-label, randomized, multicenter phase 3 study (SHR-1210-303), patients with advanced/metastatic, non-squamous NSCLC with negative EGFR or ALK were stratified by sex and smoking history (≥ 400/year versus ˂ 400/year) and were randomly assigned (1:1) to receive 4 to 6 cycles of carboplatin (AUC=5) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg), followed by pemetrexed with or without camrelizumab as maintenance therapy up to disease progression or intolerable toxicity. Treatment was given every 3 weeks. Crossover to camrelizumab monotherapy was permitted for patients in the chemotherapy arm who had confirmed disease progression. The primary endpoint was PFS per blinded independent central review according to RECIST v1.1. Secondary endpoints included ORR, DCR, DoR and OS. Data of subgroup analysis will be reported. Clinical Trials.gov number: NCT03134872.
Result
Between May 12, 2017 and Jun 6, 2018, 419 patients were randomized, among whom 205 received camrelizumab plus chemotherapy and 207 received chemotherapy treatment. After a median follow-up of 11.9 months, median PFS was 11.3 months (95% CI 9.5‒not reached) in camrelizumab plus chemotherapy arm and 8.3 months (95% CI 6.0‒9.7) in chemotherapy arm (HR 0.61 [95% CI 0.46‒0.80], p=0.0002). ORR, DCR, DoR and OS with camrelizumab plus chemotherapy were superior to chemotherapy (Table 1). Grade 3/4 adverse events occurred in 66.8% of patients in camrelizumab plus chemotherapy arm and 51.2% of patients in chemotherapy arm. There were 5 treatment-related deaths in camrelizumab plus chemotherapy arm and 4 in chemotherapy arm.
Table 1. Responses per blinded independent central review and overall survival in the total study population Camrelizumab plus chemotherapy
(n=205)Chemotherapy alone
(n=207)p-value Objective response rate 60.0% (53.0‒66.8) 39.1% (32.4‒46.1) p<0.0001 Disease control rate 87.3% (82.0‒91.6) 74.4% (67.9‒80.2) p=0.0009 Duration of response (months) 17.6 (11.6‒NR) 9.9 (8.5‒13.8) p=0.0356 Overall survival (months) NR (17.1‒NR) 20.9 (14.2‒NR) p=0.0272 Data are shown in % (95% CI) or median (95% CI). NR: not reached.
Conclusion
First-line camrelizumab plus chemotherapy shows substantial clinical benefit in patients with advanced/metastatic non-squamous NSCLC with negative EGFR or ALK in terms of PFS, ORR, and OS and acceptable safety profiles. The combination should become novel standard 1st line therapy for this population.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-16 - Resolving Resistance to Osimertinib by Combining Apatinib and Osimertinib in EGFR-Mutant NSCLC Patients (ID 860)
09:45 - 18:00 | Author(s): Jun Zhao
- Abstract
Background
There are currently limited treatment options after osimertinib resistance.Resistance to epidermal growth factor receptor(EGFR) inhibitors is frequently associated with enhanced vascular endothelial growth factor(VEGF) levels.Dual inhibition of the VEGF receptor(VEGFR) and EGFR signaling pathways has the potential to overcome osimertinib resistance. Apatinib is an oral tyrosine kinase inhibitor(TKI) against VEGFR-2. This study was conducted to evaluate the efficacy of Apatinib plus osimertinib after osimertinib resistance in EGFR-mutant NSCLC patients.
Method
The study was expected to enroll 30 EGFR-mutant NSCLC patients resistant to osimertinib. Patients received oral apatinib 250mg QD plus osimertinib 80mg qd. Efficacy evaluation was conducted after first month, then every two months once again. The primary endpoint was progression free survival (PFS).
Result
From March 01, 2018 to February 28, 2019, 23 patients were enrolled. The overall response rate(ORR) and disease control rate(DCR)of apatinib plus osimertinib after osimertinib resistance was 8.7%(2/23) and 73.9%(17/23),respectively.Until the last follow-up(March 31,2019), 17 patients (73.9%,17/23)showed disease progression,the other 6 patients (26.1%,6/23) still received combination therapy,as shown in figure 1.The median PFS was 4.0 months (95% CI 2.4-5.5).Six patients had received at least six-month combination therapy,four of whom were still on treatment.The most common adverse event was hypertension, diarrhea,rash and hand-foot syndrome.What calls for special attention is that one patient achieved partial response, however, stopped the combination therapy due to seriously decreased left ventricular ejection fraction.
Conclusion
Apatinib plus osimertinib might be a choice after osimertinib resistance.For further investigation, large sample and additional clinical trials are warranted.
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P1.14-47 - ctDNA NGS for Guiding Crizotinib Treatment in ALK-Rearranged Advanced NSCLC Patients (Pts) (Now Available) (ID 1522)
09:45 - 18:00 | Author(s): Jun Zhao
- Abstract
Background
FISH and IHC are commonly used and the golden standard for testing ALK rearrangement. However, they provide no information on fusion types or mutation status of other genes, which could be important prognostic factors. In addition, a tissue biopsy is not always applicable/preferred by pts.
Method
43 ALK-rearranged treatment naïve advanced NSCLC pts were included. ALK-rearrangement was confirmed by ctDNA NGS with a panel of 59 tumor-related genes in 25 pts (ctDNA arm) and by IHC/FISH/tissue NGS in 18 pts (control arm). All pts received crizotinib as first-line therapy. PFS was estimated using Kaplan-Meier method and compared using log-rank test.
Result
On average, Pts in ctDNA arm were significantly older at diagnosis than pts in the control arm (56 vs. 45, p = 0.02), indicating the preferability of ctDNA NGS in elderly pts. Though older, pts in ctDNA arm had a similar mPFS with pts in the control arm (8 vs. 10 mo, p = 0.9). ALK fusion types in ctDNA arm and their associated statistics were listed in Table 1. Concomitant mutations were identified in 15 genes in 9 pathways. Frequently mutated pathways include p53 (in 8 pts) and DNA repair pathways (in 3 pts). Mutations in DNA repair pathway (5 vs. 10 mo, p = 0.06), high frequency of EML4-ALK (>= 1.5%) (6 mo vs. NR, p = 0.06), and bone metastasis (6 vs. NR, p = 0.05) were associated with shorter mPFS.
Table 1. ALK fusion types and associated statisticss ALK fusion types # of pts (Median) age at diagnosis (year) (m)PFS (mo) Average # of mutations per pt V1 11 52 10 1.5 V3 10 61 6 2.8 V2 1 60 - 1 V5' 1 65 - 1 V7 1 49 3 2 DCTN1-ALK 1 47 - 2
Conclusion
Information on ALK fusion types, concomitant mutations, and mutation frequencies provided by NGS could be valuable prognostic factors and deserves further investigation. ctDNA NGS could be used as an effective alternative to identify ALK+ pts, especially for elderly pts, when tissue biopsy is inapplicable or not preferred.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-54 - Characteristic of MSI-H Lung Cancer Patients Identified with Targeted Next-Generation Sequencing (Now Available) (ID 2435)
10:15 - 18:15 | Author(s): Jun Zhao
- Abstract
Background
MSI-H/dMMR predicts response to immune oncology (IO) agents and is an approved biomarker for pembrolizumab therapy irrespective of histologic diagnosis. In this study, we retrospectively analyzed a large cohort of lung cancer patients using targeted next generation sequencing to examine the prevalence and clinicopathologic associations of MSI-H in lung cancers.
Method
MSI and TMB status was derived from a 1021 gene targeted next generation sequencing panel. MSI was analyzed using MSIsensor 0.5, that relies on an empirically defined cutoff of MSI score>10%, as MSI-H. TMB analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3 %. TMB-H pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).
Result
5592 lung cancer patients were interrogated in the study, with 4753 lung adenocarcinoma, 559 lung squamous cell carcinoma, 112 small cell lung carcinomas (SCLC), and 168 rare lung cancer types including pulmonary sarcomatoid carcinoma, carcinoid and so on. A total of 12 lung tumors were identified as MSI-H (0.21%), and 5 were lung adenocarcinoma (0.1%), 3 were small cell lung cancer (2.7%), 1 was lung squamous cell carcinoma (0.18%), 2 were pulmonary sarcomatoid carcinomas, and 1 was pulmonary carcinoid (1.8%). The incidence was higher in small cell lung cancer and rare lung cancer subtypes. The average diagnosis age of the 12 patients were 53 years (range: 16-74). All the patients were TMB-H, with the TMB averaged 51.23 mut/Mb (range: 10-70 mut/Mb). Two of the 5 lung adenocarcinoma patients carried EGFR L858R or 19del mutation. One patient who had both NRAS G12V and EGFR Ex20 mutation had tried nivolumab (120mg) for one cycle with deteriorating of cough and progression of disease.
Conclusion
MSI-H is very rare in lung tumors, where it appears to enrich in small cell lung cancer and rare lung cancer subtypes. MSI-H lung cancer patients tend to have a younger diagnosis age. MSI-H may coexist with other driver alterations, including those negatively associated with IO response. Additional investigation is needed to determine efficacy of IO in these patients.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-09 - Concurrent TP53 Mutation Adversely Impact the Efficacy of Crizotinib in ROS1-Rearranged Lung Cancer Patients (ID 2158)
10:15 - 18:15 | Author(s): Jun Zhao
- Abstract
Background
ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored.
Method
We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test.
Result
In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment.
Conclusion
Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.
