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Julie Brahmer
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ES14 - Novel Immunotherapy Strategies in NSCLC (ID 184)
- Event: WCLC 2020
- Type: Educational Session
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 11:45 - 12:45, Scientific Program Auditorium
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ES14.03 - Combining Epigenetic Therapy and Immunotherapy in NSCLC (ID 4016)
11:45 - 12:45 | Presenting Author(s): Julie Brahmer
- Abstract
- Presentation
Abstract not provided
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IS10 - Industry Symposium Sponsored by Bristol Myers Squibb: Thoracic Cancers, New Developments with IO (ID 287)
- Event: WCLC 2020
- Type: Industry Symposium
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 1/29/2021, 13:00 - 14:00, Industry Symposia Auditorium (via Industry Hub)
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IS10.03 - IO in the Treatment of Metastatic NSCLC, Where Are We Now? (ID 4351)
13:00 - 14:00 | Presenting Author(s): Julie Brahmer
- Abstract
Abstract not provided
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IS10.04 - Non-Metastatic and Metastatic NSCLC Q&A (ID 4352)
13:00 - 14:00 | Presenting Author(s): Julie Brahmer
- Abstract
Abstract not provided
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IS11 - Industry Symposium Sponsored by Amgen Oncology: Advancing the Next Frontier of Innovation in Lung Cancer Therapies (ID 288)
- Event: WCLC 2020
- Type: Industry Symposium
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 13:00 - 14:00, Industry Symposia Auditorium (via Industry Hub)
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IS11.04 - Emerging Novel Targets for Lung Cancer (ID 4358)
13:00 - 14:00 | Presenting Author(s): Julie Brahmer
- Abstract
Abstract not provided
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MA07 - Improving Care for People with Lung Cancer: Decision Making, Survivorship, and New Challenges During COVID-19 (ID 167)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Patient Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 15:30 - 16:30, Scientific Program Auditorium
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MA07.05 - Survivors from Anti-PD-(L)1 Immunotherapy in NSCLC: Clinical Features, Survival Outcomes and Long-term Toxicities (ID 3411)
15:30 - 16:30 | Author(s): Julie Brahmer
- Abstract
- Presentation
Introduction
Anti-PD-(L)1 immunotherapy (IO) leads to prolonged survival in selected patients (pts) with advanced non-small cell lung cancer (NSCLC). The clinical features, survival outcomes and long-term toxicities of NSCLC pts alive >1 year from IO start are poorly understood.
Methods
Pts with histologically-confirmed stage III/IV NSCLC alive >1 year after IO start were defined as IO survivors, and identified from an IRB-approved institutional database between 11/2009-2/2020. Demographics, treatment, immune-related adverse events (irAEs) were identified via retrospective chart review. Overall survival (OS) was defined as time from IO start until death from any cause.
Results
Of 317 NSCLC pts treated with IO, 114 NSCLC survivors were identified (36%). The median age was 66 years (range: 42-87), most were male (54%), former/current smokers (82%), with adenocarcinomas (67%, 76/114), and 34% harbored KRAS mutations (32/114). Most pts received standard-of-care IO (52%, 59/114) in the 1st/2nd-line setting (82%, 94/114), and nivolumab was the most common IO given (nivo=39%; nivo/ipi=11%; pembro= 18%; durva= 7%; other anti-PD-(L)1= 1%; PD-(L)1+chemo= 11%; PD-(L)-1+other= 13%). Median number of IO doses received was 13 (range: 1-121). Median OS was 26.5 mos (range 12.2-106.9 mos), and median PFS was 13 mos (range: 0.7-106.9 mos) in the entire cohort. Most IO survivors (52%, 59/114) experienced an irAE of any-grade (1 irAE= 34%; 2 irAEs= 11%; 3+ irAEs= 7%). Development of an irAE was associated with improved median PFS (irAE: = 21.2 mos, no irAE:= 9.8 mos, p=0.002), but not OS (irAE: 28.5 mos vs. no irAE: 24.5 mos, p= 0.28). The most common irAEs were pneumonitis (18%), dermatitis (11%), and inflammatory arthritis (IA) (11%), and the majority were low grade (CTCAE Grade 1-2= 78%, 73/94; Grade 3+= 22%, 21/94). Median time to onset of first irAE was 3.5 mos (range 0-33.7 mos). Most were treated with steroids alone (51%, 30/59) or with additional immunosuppression (12%, 7/59). irAEs led to discontinuation of IO in 29 survivors (25%). Of IO survivors experiencing irAEs, 59% (35/59) had ongoing irAEs at time of death or last follow-up. Seven IO survivors developed irAEs after discontinuation of IO therapy (IA=3, IA and colitis= 1, colitis =1, pruritus =1, aplastic anemia=1). The majority of IO survivors (51%, 31/59) were still receiving treatment for pneumonitis (4), thyroid dysfunction (10), hypophysitis (3), IA (5), colitis (4), dermatitis (4), Type 1 Diabetes (1), and pancreatitis (1) 1-year post IO start. Almost half (45%, 14/31) were still on steroids, and 16% (5/31) were on additional immunosuppression (methotrexate, cyclosporine, and mycophenolate).
Conclusion
In a real-world cohort, 36% of NSCLC pts survived >1 year after IO start, with an unprecedented median OS of 26.5 months. The majority of IO survivors developed irAEs, more than half of which had long-term irAEs requiring ongoing immunosuppressive management 1-year post IO start. These data could be used to develop an IO survivorship program, focusing on long-term toxicity management.
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P05 - Early Stage/Localized Disease - Radiotherapy (ID 114)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P05.04 - Association of Lymphopenia and Disease Progression in Unresectable NSCLC Treated with Definitive Chemoradiation and Immunotherapy (ID 3020)
00:00 - 00:00 | Author(s): Julie Brahmer
- Abstract
Introduction
Concurrent chemoradiation followed by consolidative immunotherapy is the current standard of care for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC). Treatment-related lymphopenia (TRL) is a common side effect of this treatment paradigm. As immunotherapy is mechanistically dependent on functional T-lymphocytes, TRL may compromise the efficacy of these agents. The association between TRL and worse outcomes is demonstrated in other solid but remains unexplored in NSCLC patients receiving chemoradiation and immunotherapy. Here, we investigate the interplay between TRL and disease progression in the definitive setting.
Methods
Patients with NSCLC treated with curative intent from 2015-2019 at a tertiary academic institution were retrospectively identified. Inclusion criteria included: pathologic diagnosis of NSCLC, stage IIB-IIIC disease (AJCC 8th ed.), and receipt of concurrent chemoradiation followed by immunotherapy. Absolute lymphocyte count (ALC) and neutrophil to lymphocyte ratio (NLR) were recorded before the initiation of chemoradiation and before adjuvant immunotherapy. ALC was classified as normal (>1000 cells/mm3) or abnormal (<1000 cells/mm3). Severe lymphopenia was defined as grade III/IV toxicity (<500 cells/mm3) and NLR was examined at a cutoff of >4 vs. <4. Progression-free survival (PFS) was calculated via Kaplan-Meier methodology. Univariate and multivariate Cox Proportional Hazard modeling was used to assess the relationship between clinical variables and disease outcome. Immune-related adverse events (irAEs) and all toxicity was recorded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Results
At analysis, 78 patients who received definitive chemoradiation and initiated adjuvant immunotherapy were identified. The median follow-up time was 321 days (IQR 291-565). The median age was 66 years (IQR: 58-73), 55% were males, and 88% had a KPS of >70. Radiation was delivered in conventionally fractionated doses (total Gy, median: 63 Gy, IQR: 61.2-66). At baseline, 90% (n=70) of patients had a normal ALC and one patient had severe lymphopenia. After chemoradiation, the median ALC decreased from 1520 cells/mm3 (IQR: 1230-1980) to 715 cells/mm3 (IQR: 520-940), 22% of patients had a normal ALC, and 23% of patients developed severe lymphopenia. Median PFS estimation for the entire cohort was 475 days (IQR: 262 – NR). Patients who initiated adjuvant immunotherapy with severe lymphopenia had worse PFS than those who did not (median 217 days [IQR: 120-434] vs. 570 days [IQR: 401-NR], p<0.001). Cox multivariate modeling further confirmed severe lymphopenia at the time of immunotherapy initiation was associated with a higher hazard of progression (HR 4.90, p<0.001). There was no significant difference in the number of grade 3+ irAEs in patients who were severely lymphopenic versus those who were not. There was no difference in PFS in patients according to NLR stratification. Overall survival (OS) was not able to be assessed due as data are still maturing.
Conclusion
This is the first report of severe TRL associated with disease progression in patients with locally advanced NSCLC receiving consolidative immunotherapy. The iatrogenic side effects of therapy must be weighed against its potential benefits and factors associated with the development of lymphopenia should be addressed. Future directions should consider strategies to mitigate TRL in order to enhance tumor immunogenicity.
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P21 - Locoregional and Oligometastatic Disease - Treatment of Locally Advanced NSCLC (ID 131)
- Event: WCLC 2020
- Type: Posters
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P21.04 - Comparing Outcomes for Patients Receiving Chemoradiation Followed by Surgery vs. Immune Checkpoint Inhibitors in Non Small Cell Lung Cancer (ID 3758)
00:00 - 00:00 | Author(s): Julie Brahmer
- Abstract
Introduction
A clinical decision-making branch point arises when considering patients with locally advanced non small cell lung cancer (NSCLC). Surgery remains the considered treatment in patients with low bulk and single nodal station disease, while in those with stage III-N2 disease, the optimal local therapy is controversial. In patients with unresectable NSCLC – chemoradiation (CRT) followed by Immune Checkpoint Inhibitor (ICI) consolidation shows improved survival over CRT alone. We compare clinical outcomes between patients receiving trimodality care and those receiving consolidative immunotherapy.
Methods
We conducted a retrospective review of patients diagnosed with NSCLC who had received definitive CRT between 2015 – 2019 at a single tertiary medical center. The decision for surgical feasibility was determined at diagnosis, prior to CRT. Group 1 included patients that had undergone definitive CRT followed by surgery (CRT+S). Group 2 included patients that received definitive CRT followed by consolidation with ICI (CRT + ICI). Stage IIIB patients were predominantly in Group 2 (n=39,49.4%) than Group 1 (n=3,9.7%). We analyzed OS and PFS using Kaplan Meier analyses and compared groups using the log-rank test. Median follow-up was calculated using a reverse Kaplan Meier approach. We also performed univariable and multivariable Cox modeling.
Results
Thirty-one patients were included in Group 1 (median age 66.0 years, 67% female) while seventy-nine patients were in Group 2 (median age 66.4 years, 45% female). When assessing OS, median follow-up time was 34.5 months (Interquartile Range [IQR] 24.7- 42.4 months] in Group 1 vs 11.5 months (IQR 9.7- 19.9 months) in Group 2. (p<0.0001). During the course of follow-up, five (16.1%) patients in Group 1 died and 14 (17.7%) patients in Group 2 died. Neither group reached median survival at the time of analysis. Survival curves for both groups were significantly different (log rank p = .005) and Cox modeling confirmed a lower hazard of death among patients receiving CRT +S (HR = 0.162, p=.02). When assessing PFS, median follow-up time was 32.5 months (IQR 22.9 – 42.4 months) in Group 1 vs 11.5 months (IQR 9.6 – 16.9 months) in Group 2 (p <0.0001). During follow-up, 11 (35.5%) patients in Group 1 experienced disease progression compared to 30 (38%) patients in Group 2. Group 1 did not reach median PFS at the time of analysis; Group 2 reached median PFS at 16.7 months (IQR 12.8 – NR). PFS curves for both groups were significantly different (log rank p = .0274), and after adjusting for all covariates Cox modeling confirmed a lower hazard of disease progression among patients receiving CRT +S (HR = 0.411, p= 0.0296).
Conclusion
We explore differences in clinical outcomes between patients receiving surgery verus ICI following definitive CRT – with results demonstrating that pursuing surgery leads to a higher probability of OS and PFS. This study is limited by its retrospective nature and disparate patient groups. Nevertheless, our findings suggest that surgery may have a role in lung cancer management in the era of ICIs. With continuing improvements in surgical and immunotherapy paradigms, the optimal treatment remains unclear and warrants prospective investigation.
