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Bruce E Johnson
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.09 - Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) (ID 12941)
14:30 - 14:35 | Author(s): Bruce E Johnson
- Abstract
- Presentation
Background
Cisplatin-based chemotherapy, before or after surgery, provides only a 5% benefit in 5yr. OS in resectable NSCLC. A 20 patient study (NEJM April 2018) showed that preoperative immune checkpoint inhibitor therapy yielded a clinically meaningful major pathologic response rate (MPR ≤10% residual viable tumor cells) and did not delay or complicate surgery. This large multicenter trial measures MPR and biomarkers of benefit using neoadjuvant atezolizumab (atezo) [NCT02927301].
a9ded1e5ce5d75814730bb4caaf49419 Method
We planned 2 cycles of atezo (1200mg, days 1, 22) in patients with stages IB -selected IIIB resectable NSCLC prior to surgical resection (day 40 +/- 10). Chest CT, PET were planned pre-atezo and presurgery to assess response. Primary tumor +/- node biopsies and blood samples were obtained before atezo and presurgery for biomarker studies. The primary endpoint was MPR. Secondary endpoints included safety, response by PD-L1, OS, and DFS.
4c3880bb027f159e801041b1021e88e8 Result
For this updated efficacy and safety analysis (Feb’18 datacut), we report first 54 of 180 planned pts: 29 males, median age 65 yr, all ECOG 0-1; 17 current, 33 former smokers; 35 non-squamous NSCLC; clinical stages Ib/IIa/IIb/IIIa/IIIb = 5/11/13/20/5. Two pts received one dose of atezo due to treatment related AE (Gr 1 pyrexia, Gr 2 dyspnea) but underwent uncomplicated resection with MPR assessment. There was 1 unrelated Gr 5 AE (sudden cardiac death post surgical resection), 16 Gr 3-4 AEs (3 treatment related). Surgery was delayed in 1 pt due to Gr3 pneumonitis. By RECIST, 3 pts had PR, and 49 had SD. 50 pts underwent surgery and 47 pts had MPR assessment: 2 pts discontinued study preop due to radiographic PD and 2 discontinued due to other reasons; 3 pts had unresectable disease. MPR rate was 10/50 (20%, 95% CI 10-34%) including 3 pts who had pCR (no viable tumor cells) in the primary tumor. Excluding 5 pts who had known driver mutations (4 EGFR+, 1 ALK+), MPR rate was 10/45 (22%, 95% CI 11-37%). PD-L1 status was evaluable in 44/54 pts; 8/10 pts with MPR had PD-L1+ status and 2 had unknown PD-L1 status; 8/28 PDL-1 (+) patients had MPR (29%).
8eea62084ca7e541d918e823422bd82e Conclusion
In a multicenter study, neoadjuvant atezo was well tolerated. MPR rate is encouraging. Clinical and pathological responses are often discordant. Correlative analyses on pre- and post atezo tissues are ongoing. Preliminary correlative analyses in blood samples are included in a separate abstract.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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MA04.10 - Comprehensive Peripheral Blood Immunophenotyping and T-Cell Clonal Analysis During Neoadjuvant Immunotherapy with Atezolizumab in NSCLC (ID 13118)
14:35 - 14:40 | Author(s): Bruce E Johnson
- Abstract
- Presentation
Background
Immune-checkpoint blockade targeting PD-L1/PD-1 to activate anti-tumor immunity is associated with improved response rates and survival compared to chemotherapy in selected metastatic NSCLC patients. Evaluation of the pre-therapeutic immune profile and its treatment-related evolution associated with clinical benefit will guide future immunotherapy development and support clinical decision-making. Here, we present an analysis of peripheral blood (PB) immunophenotyping and T-cell-receptor (TCR) clonality before and after immunotherapy from an ongoing 180-patient phase II study of atezolizumab as neoadjuvant therapy with stage IB-IIIB resectable NSCLC (NCT02927301; LCMC3).
a9ded1e5ce5d75814730bb4caaf49419 Method
As of February 5th datacut, the first 54 enrolled and dosed patients are presented. The biomarker evaluable population (BEP) further subset to patients with paired PB samples analyzed within 72 hours after collection and a major pathological response (MPR) assessment. Comprehensive immune cell phenotyping (10-color flow cytometry, IMMUNOME) and TCR-Vß-analysis by flow cytometry were performed. Immunoprofile analyses were correlated with atezolizumab treatment, pathological response and PD-L1 expression.
4c3880bb027f159e801041b1021e88e8 Result
In this ongoing analysis, BEP included 31 patients. 5 patients (16%, 95% CI (5%, 34%)) had a MPR; all of which stained positive for PD-L1 by IHC using 22C3 (TPS≥1%) and SP142 (PD-L1 expression on ≥1% tumor cells (TC) and/or tumor infiltrating immune cells (IC)) at baseline. We observed significant increases in natural killer (NK) cells (p=0.005) and CD8+ T-cells (p=0.031) and a Th1-response related dendritic cell (DC) subpopulation (p=0.031) and significant decreases in B-cells (p=0.015) after treatment.
Patients who achieved MPR show lower baseline levels of degranulated CD8+ T-cells (p=0.015), late-activated NK-cells (p=0.043), memory CD4+ (p=0.048) and memory CD8+ T-cells (p=0.032); changes in PB NK-cells (p=0.041), a decrease in M-MDSCs and a Th-2 and Th-17-response related DC subpopulation (p=0.043) in response to treatment were noted in patients with MPR versus non-MPR.
Among the 16 patients with TC/IC 1/2/3 (> 1% PD-L1 expression) the following significant differences were observed compared to TC0/IC0 (7 patients): higher levels of late-activated CD4+ T-cells (p=0.025) and mid-activated CD8+ T-cells (p=0.044) at baseline, decrease of senescent T-cells (p=0.041), monocytic myeloid-suppressor cell subpopulations (M-MDSCs) and an increase in a Th1-response related DC subpopulation (p=0.026) after treatment.
TCR clonality analysis showed expansions in Vß-subtypes after atezolizumab treatment.
8eea62084ca7e541d918e823422bd82e Conclusion
Immunophenotyping and TCR-Vß-repertoire analysis in peripheral blood samples from NSCLC patients treated with neoadjuvant atezolizumab show differences in immune cell subsets in baseline samples and changes after treatment.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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MA25.09 - M1b Disease in the 8th Edition of IASLC Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcom (ID 11942)
14:30 - 14:35 | Author(s): Bruce E Johnson
- Abstract
- Presentation
Background
The 8th edition of IASLC staging of lung cancer has revised M classification and defined M1b disease for single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence of M1b disease in stage IV NSCLC patients (pts), and studied the pattern of single extrathoracic metastasis and its relationship with overall survival (OS).
a9ded1e5ce5d75814730bb4caaf49419 Method
567 pts with stage IV NSCLC (236 males, 331 females, median age: 63) diagnosed in 2008-2012 were reviewed to determine M stage according to the 8th edition of IASLC staging of lung cancer (M1a: separate tumor nodules in a contralateral lobe, pleural/pericardial nodule or effusion; M1b: single extrathoracic metastasis; M1c: multiple extrathoracic metastasis in one or more organs). Clinical characteristics and OS were compared according to M stage.
4c3880bb027f159e801041b1021e88e8 Result
Among 567 pts, 57 pts (10%; 95%CI: 7.6-13%) had M1b disease with single extrathoracic metastasis, while 119 pts (21%) had M1a and 391 pts (69%) had M1c disease. Squamous histology was more common in M1b (9/57; 16%) than in M1a (7/119; 6%) and M1c pts (22/391; 6%) (Fisher P=0.03). The median OS of M1b pts was 14.8 months (95%CI: 12.7-24.7 months), compared to 22.7 months (95%CI: 18.5-31.6 months) for M1a and 13.4 months (95%CI: 11.8-15.3 months) for M1c pts (log-rank P < 0.0001). Among 57 M1b pts, brain was the most common site of single metastasis (n=28; 49%), followed by bone (n=16; 28%), adrenal (n=7; 12%), liver (n=3; 5%), muscle (n=2; 4%), and distant node (n=1; 2%). M1b pts with liver metastasis had shorter OS than others (median OS: 8.1 vs. 16.1 months, log-rank P=0.046). Single metastasis in M1b pts were locally treated in 31 pts (54.5%). Brain metastasis was more frequently treated with local treatment than others (26/28, 92.9%vs. 5/29, 17%; p<0.0001).
8eea62084ca7e541d918e823422bd82e Conclusion
M1b disease was noted in 10% of stage IV NSCLC pts. Squamous histology was more common in M1b than in M1a and M1c groups. Brain was the most common site of single metastasis and was often treated locally. Single liver metastasis in M1b disease was associated with shorter OS. The study characterized the unique clinical features of the new category of M1b disease among stage IV NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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MS08 - Lung Cancer in the Real World (ID 787)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 201 F
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MS08.04 - The ASCO Perspective (ID 11434)
14:15 - 14:30 | Presenting Author(s): Bruce E Johnson
- Abstract
- Presentation
Abstract not provided
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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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-35 - Tumor Volume Analysis In ALK-Rearranged NSCLC Treated with Crizotinib: Identifying an Early Marker for Clinical Outcome (ID 11720)
16:45 - 18:00 | Author(s): Bruce E Johnson
- Abstract
Background
Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK-rearrangement. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early imaging marker that can predict clinical outcome.
a9ded1e5ce5d75814730bb4caaf49419 Method
Forty-two patients with advanced NSCLC harboring ALK-rearrangement (15 men, 27 women; median age: 55.7 years) treated with crizotinib as their first ALK-directed therapy at Dana-Farber Cancer Institute between November 2008 and June 2016. All patients had a follow-up chest CT scan at 8 +/- 3 weeks of therapy and had a dominant measurable lesion in the lung (≥1 cm) on baseline CT. Tumor volume of the dominant lung lesion was measured on baseline CT and follow-up CT at 8 +/- 3 weeks of therapy, using the previously validated technique on the volume analysis software (Vitrea ; Vital Images, Minnetonka, MN). The relationships between the 8-week volume change (%) and overall survival (OS) measured from the 8-week scan date were studied.
4c3880bb027f159e801041b1021e88e8 Result
The 8-week tumor volume change ranged from -99.3% to 117.5% (median: -57.7%). Using the 25 percentile of the 8-week volume change of -74%, 11 patients with >74% volume decrease at 8 weeks had a significantly longer OS compared to 31 patients with ≤74% decrease (Median OS: 92.0 months vs. 22.8 months, log-rank p=0.0048). In multivariable analyses using Cox proportional hazards models, the 8-week volume decrease of >74% remained as a significant factor associated with prolonged OS (HR=0.14, 95%CI: 0.03-0.59; Cox p=0.008) after adjusting for other significant variables including tumor stage at presentation (stage IV vs. others, HR=5.6, 95%CI: 1.29-24.3; p=0.02). Of the 31 patients with ≤74% decrease on the 8-week scan, best overall response by RECIST was partial response (PR) in 21 (68%), stable disease in 9 (29%), and progressive disease (PD) in one (3%). None of the 42 patients experienced RECIST-PD prior to the 8-week scan.
8eea62084ca7e541d918e823422bd82e Conclusion
The 8-week tumor volume decrease of >74% on CT is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib. The 8-week tumor volume analysis helps to identify patients who may benefit from alternative therapy in the early course of crizotinib therapy.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-73 - Automated Image Analysis Tool for Tumor Volume Growth Rate to Guide Precision Cancer Therapy: EGFR-Mutant NSCLC as a Paradigm (ID 11971)
16:45 - 18:00 | Author(s): Bruce E Johnson
- Abstract
Background
Imaging remains a crucial component in the evaluation of the therapeutic benefit of precision cancer therapy, because it objectively characterizes tumor burden changes during therapy and provides guides for treatment decisions. The purpose of the present study is to develop an automated analytic module for calculation of tumor growth rate from serial CT scans and evaluate the module functionality and reproducibility in a pilot cohort of advanced NSCLC patients with EGFR mutations treated with EGFR tyrosine kinase inhibitors.
a9ded1e5ce5d75814730bb4caaf49419 Method
The module utilized a commercially available image-processing workstation equipped with a validated tumor volume measurement tool. A novel analytic software module was programmed with the capability to record and display serial tumor volume changes and to calculate tumor volume growth rate over time and added to the workstation. The functionality and reproducibility of the module was evaluated using a pilot cohort of 24 EGFR-mutant patients treated with EGFR inhibitors by two independent thoracic radiologists.
4c3880bb027f159e801041b1021e88e8 Result
The module analyzed chest CT scans from 24 patients (5 males, 19 females; median age: 61) with a median of 8 scans per patient, totaling 227 scans and provided a graphical display with an automated calculation of tumor growth rate after the nadir volume for each patient. High inter and intraobserver agreements were noted for tumor growth rates, with concordance correlation coefficients of 0.9323 and 0.9668, respectively. Interpretation of slow versus fast tumor growth using previously identified threshold of ≤0.15/month had a perfect interobserver agreement (κ=1.00), and an excellent intraobserver agreement (κ=0.895).
8eea62084ca7e541d918e823422bd82e Conclusion
The present study describes the development of an image analytic module for assessing tumor growth rate and the data demonstrates the functionality and reproducibility of the module in a pilot cohort of EGFR-mutant NSCLC patients treated with EGFR-TKI. The image analytic module is an initial step for clinical translation of the tumor growth rate approach to guide cancer treatment in precision oncology.
6f8b794f3246b0c1e1780bb4d4d5dc53
