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Jean-Baptiste Assié
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.09 - Dramatic Responses to Immune Checkpoint Inhibitors in MET Exon 14 Skipping Mutation (METex14mut) Non Small Cell Lung Cancers (Now Available) (ID 1621)
10:30 - 12:00 | Author(s): Jean-Baptiste Assié
- Abstract
- Presentation
Background
METex14 mutations occur in 2-3% of Non-Small-Cell Lung Cancers (NSCLC), with a higher prevalence in patients aged over 70-years-old, non-smokers.and women. Crizotinib, a MET-inhibitor, allows remarkable, but often short, tumor responses. Immune Checkpoint Inhibitors (ICIs) have become pivotal treatments in NSCLC but seem less efficient in non-smokers and in case of oncogenic addiction. We report durable strong responses in four non-smoker women (A, B, C, D) and two smokers (E, F) treated by ICIs in a second-line setting for NSCLC harboring METex14 mut.
Method
We studied the clinical and biological characteristics and the tumor response after ICIs for each patient. The complete DNA sequencing of the tumor was available after the beginning of ICIs (explaining why crizotinib was not proposed in second line). PDL1 expression on tumor cells was evaluated by antibody clone E1L3N (Cell signaling Technology).
Result
Table 1 summarizes patient and tumor characteristics, and the evolution during ICIs : Nivolumab for all patients except E (pembrolizumab). There were neither EGFR, BRAF, KRAS mutations, nor ALK or ROS translocations (except minority KRAS mutation for C). No concurrent MET amplification was found.
Partial or complete response was rapidly (2 months) obtained in five patients, while pseudo-progression was first observed in D. After a grade 3 diarrhea and diabetic ketoacidosis, ICI was stopped in A but the reintroduction one year later did not cause any toxicity. The tolerance was excellent for the 5 other patients. Response was maintained from 16 to 40 months and treatment is ongoing in four patients. C stopped ICI after 26 months (Complete response on PETscan). B had an isolated bone progression after 7 months of ICI which benefited from a local radiotherapy. After almost 2 years of ICI, a multisite progression occurred and crizotinib was proposed.
Conclusion
ICIs should be discussed in the treatment of METex14 mut NSCLC.
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MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:David R Spigel, Roberto Ferrara
- Coordinates: 9/08/2019, 13:30 - 15:00, Vancouver (2003)
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MA07.05 - Immune Checkpoint Inhibitor (ICPi) Re-Challenge: Outcomes Analysis in a French National Cohort of Non-Small-Cell Lung Cancer (NSCLC) Patients (Now Available) (ID 1903)
13:30 - 15:00 | Author(s): Jean-Baptiste Assié
- Abstract
- Presentation
Background
Anti-PD1/PDL1 deeply changed the NSCLC therapeutic algorithm in the past few years. Unfortunately, a majority of patients experiences disease progression. ICPis re-challenge could be an attractive option but no data supporting this strategy are available. Here we report outcomes of a large cohort of NSCLC patients treated with anti-PD1/PDL1 re-challenge.
Method
We retrospectively collected data about 144 advanced NSCLC patients (diagnosis between 2010 and 2018) from 26 French centers. Patients were re-challenged with ICPis after at least 12 weeks of discontinuation for toxicity, disease progression or clinical decision. Progression Free Survival (PFS) and Overall Survival (OS) were calculated from the start of first or second ICPi to disease progression (PFS1;PFSR) and death or last follow-up (OS1;OS2) respectively.
Result
Median age was 63 year [39 –83], most of patients were male (67%), smokers (87%), adenocarcinomas (62%) and stage IV at diagnosis (66%). Most of patients received the first ICPi round in first or second line (66%) and the second ICPi round in third line or later (79%). In both settings patients received preferentially an anti-PD1 (87%) and no differences were detected regarding brain metastasis or ECOG PS (P = 1.10-1 and P = 1.10-1 respectively). The Best Response during the re-challenge was not associated to that one achieved to the first ICPi (P = 1.10-1). The median PFS1 and PFSR were 13 months [95% CI 10-16.5] and 4.4 months [95% CI 3-6.5] respectively. PFSR was longer in patients discontinued because of clinical decision (6.5 months [95% CI 2.5-11.9]) or toxicity (5.8 months [95%CI 3.5-18]) compared to disease progression (2.9 months [95% CI 2.0-4.4]) (P = 2.10-2) and in those not receiving chemotherapy between the two ICPis (5.8 months [95%CI 4.1-10.5]) compared to those who did (3.0 months [95% CI 2.0-4.4])(P = 2.10-3). Median OS1 was 3.3 years [95% CI 2.9-3.9] without differences according to the discontinuation reason (P =2.10-1). Median OS2 was 1.5 y [95%CI 1.0-2.1] and was longer in patients discontinuing the first ICPi due to toxicity (2.1y [95%CI 1.4-NR]) compared to disease progression (1.0y [95%CI 0.4-1.5]) or clinical decision (1.5y [95%CI 0.4-NR]) (P = 3.10-2). Neither OS1 nor OS2 were affected by treatments received between the two ICPis (P = 3.10-1 and P = 1.10-1 respectively).
Conclusion
ICPis re-challenge might be a useful option mainly in patients discontinuing the first ICPi because of toxicity or clinical decision and in those able to keep a treatment-free period between the two ICPis.
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MA07.06 - Immunotherapy Re-Challenge After Nivolumab Treatment in Advanced Non-Small Cell Lung Cancer in French Real-World Setting (Now Available) (ID 1281)
13:30 - 15:00 | Author(s): Jean-Baptiste Assié
- Abstract
- Presentation
Background
Real‐world evidence of nivolumab as treatment for advanced non-small cell lung cancer (aNSCLC) can complement evidence from clinical trials to optimize routine usage and personalization of care. Further, little is known about treatment options and outcomes after discontinuation of nivolumab.
Method
Based on the National hospitals database (PMSI), we built a retrospective cohort of all NSCLC patients (ICD code: C34*) starting nivolumab in 2015-2016 and followed them until Dec 2017. Information on patients’ baseline characteristics (demographics, comorbidities, treatment history) was retrieved. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Time to treatment discontinuation (TTD) and overall survival (OS) were estimated with Kaplan-Meier methodology. Re-challenged patients were analyzed according to their first nivolumab treatment duration i.e. <3; 3-6; ≥6 months.
Result
We identified 10,452 NSCLC patients initiating nivolumab during the inclusion period (male: 71%; mean age; 63.8±9.6 years; squamous histology: 44%; cerebral metastasis: 17.4%; median aNSCLC history: 12.5 months; previous curative surgery: 15.6%; median time since first chemotherapy: 10.5 months; mean dose of nivolumab: 213±54mg). Median TTD and OS were 2.8 months and 11.6 months. One-year and 2-year OS rates were 48.8% and 27.4%. Overall, 5118 (53.4%) patients received subsequent systemic therapy after nivolumab discontinuation. Among them, 1517 patients (29.6%) were re-treated with anti-PD1 agents (nivolumab: 98.8%) either after a therapeutic break (‘immunotherapy resumption group’: n=1127; mTTD: 4.1 months; mOS: 14.9 months from second initiation) or after chemotherapy (‘immunotherapy re-challenge group’: n=390; mTTD: 3.0 months; mOS: 18.2 months from second initiation). The Figure presents OS curves of the ‘re-challenge group’ according to first nivolumab treatment duration.
Conclusion
After nivolumab discontinuation, around 30% of patients received immunotherapy again, either as a resumption or as a re-challenge following non-immunotherapy treatment. The influence of the first nivolumab treatment duration on re-challenged patients' OS should be further investigated.
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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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-03 - Nivolumab Outcomes in Octogenarian Patients with Advanced Non-Small Cell Lung Cancer in French Real-World Setting (ID 1974)
10:15 - 18:15 | Author(s): Jean-Baptiste Assié
- Abstract
Background
Around 10% of patients newly diagnosed non-small cell lung cancer (NSCLC) in France are octogenarian. Knowledge about nivolumab outcomes in such specific population is still limited and real-world data represent a valuable source of information. The aim of this study was to examine use and outcomes of nivolumab in elderly patients aged ≥80 years.
Method
Based on the National hospitals database (PMSI), we built a retrospective cohort of all NSCLC patients (ICD code: C34*) initiating nivolumab in 2015-2016 in second- or later-line setting and followed them until Dec 2017. Information on patients’ baseline characteristics (demographics, comorbidities, treatment history) was retrieved for elderly (≥80 years) and non-elderly (<80 years), and time to treatment discontinuation (TTD) with nivolumab and overall survival (OS) were estimated with Kaplan-Meier methodology.
Result
Among 10,452 NSCLC patients initiating nivolumab during the inclusion period, 514 (4.9%) were 80 years or over. Mean age at baseline was 82.5 years (±2.4) in elderly and 62.8 years (±8.8) in non-elderly. Compared to non-elderly, patients were more frequently men in elderly group (p<0.001) and had more frequently prevalent hypertension and diabetes (p<0.001). Cerebral metastasis, renal failure, COPD, pulmonary insufficiency and other pulmonary chronic diseases were statistically less frequent in the elderly group (p<0.001). TTD curves showed identical median of treatment duration between both groups (2.8 months). Median OS were found similar between elderly and non-elderly patients (11.5 vs 11.6 months) and, long-term survivals were also comparable with 1-year and 2-year OS rates. Characteristics and outcomes are presented in the table.
ConclusionCharacteristics and outcomes < 80 years
(N=9938)≥ 80 years
(N=514)p-value Demographics Gender – Male 7019 (70.6%) 401 (78%) < 0.001 Mean age (±SD) 62.8 y (±8.8) 82.5 y (±2.4) < 0.001 Median age (Q1-Q3) 64 y (57-69) 82 y (81-84) < 0.001 Comorbidities Hypertension 1844 (18.6%) 142 (27.6%) < 0.001 Diabetes 871 (8.8%) 63 (12.3%) < 0.001 Renal failure 460 (4.6 %) 19 (3.7%) < 0.001 Chronic obstructive pulmonary disease 1298 (13.1%) 50 (9.7%) < 0.001 Pulmonary insufficiency 149 (1.5%) 4 (0.8%) < 0.001 Other chronic pulmonary diseases 870 (8.8%) 33 (6.4%) < 0.001 Cerebral metastasis 1771 (17.8%) 29 (5.6%) < 0.001 Lung cancer management care Diagnosis to nivolumab initiation - Median (Q1–Q3) 12.4 mo (6.7–24.0) 14.2 mo (7.9–29.9) 0.002 Nivolumab TTD - Median (Q1–Q3) 2.8 mo (1.4–6.7) 2.8 mo (1.5–6.5) N.S. Nivolumab discontinuation 9120 (91.8%) 473 (92.0%) N.S. Subsequent systemic treatment 4908 (53.8%) 210 (44.4%) < 0.001 Overall survival (OS) Median OS (Q1 –Q3) 11.6 mo (4.1-26.2) 11.5 mo (5.0-25.2) N.S. 1-year OS rate 48.8% 47.5% N.S. 2-year OS rate 27.3% 25.8% N.S. N.S.: non significant ; TTD: time to discontinuation
A small percentage of patients initiating nivolumab during the study period were aged 80 years or over (<5%). Elderly profile suggests a cautious selection by clinicians, which may also explain similar outcomes than ones in the non-elderly population.
