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Matteo Giaj Levra
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ES18 - Acquired Resistance to TKIs: The Rebiopsy Case and the Future Options (ID 21)
- Event: WCLC 2019
- Type: Educational Session
- Track: Targeted Therapy
- Presentations: 4
- Now Available
- Moderators:Teresa Moran, Matteo Giaj Levra
- Coordinates: 9/09/2019, 11:00 - 12:30, Vienna (2016)
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ES18.01 - Rebiopsy in Oncogene Addicted NSCLC at Progression (Now Available) (ID 3252)
11:00 - 12:30 | Presenting Author(s): D. Ross Camidge
- Abstract
- Presentation
Abstract
As we have defined piecharts of different oncogenes at diagnosis in NSCLC, each oncogene, under the selection pressure of an active targeted agent may develop acquired resistance after initial benefit in a number of different ways, allowing intra-oncogene piecharts of acquired resistance mechanisms to be described.
Key features to consider when considering a rebiopsy - either of the tumor or of a surrogate of the tumor (cf-DNA) is the ease and risks of rebiopsy, its false positive and false negative rates and the potential 'actionability' of the data generated. These factors allow rebiopsies for research purposes to be differentiated from those that could inform changes in clinical care immediately.
Rebiopsies of systemic disease, became standard when osimertinib was used post 1st- or 2nd-generation EGFR TKIs to look for T790M. With the move of osimertinib to the first line setting, the need to detect T790M has becoem less, but other mechanisms of resistance in the post 1/2nd generation EGFR TKI setting, separate from T790M, and in the post-osimertinib setting including small cell transition and MET amplification are also likely to change clinical management and maintain the role for biopsies in EGFR mutant disease.
In ROS1 rearranged lung cancer - the lack of efficacy of lorlatinib and crizotinib to G2032R clinically, but the possible activity of repotrectinib in trials, can make the case for a rebiopsy and reanalysis post-crizotinib or lorlatinib in ROS1+ disease. Actionable second drivers remain under exploration.
In ALK rearranged lung cancer, on target mutations are multiple - preclinical data suggesting specific drugs for specific mutations post-crizotinib can be identified remains partially determined, with multiple caveats about the preclinical-clinical transferability of data. The ALK master protocol will address some of these issues. However, perhaps the biggest issue relates to the potential for non-ALK related second drivers to be actionable, suggesting the methodology of testing in the acquired resistance setting, as in EGFR, should be broad.
Rebiopsies performed in the setting of CNS progression, in the absence of prior overt CNS benefit, are of limited practicality or use at present, however, with the advent of CNS penetrant drugs for key oncogenes, true CNS acquired resistance may emerge and some form of CNS sampling may become relevant.
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ES18.02 - When to Switch to a New TKI : Imaging Based Crtieria or Positive Liquid Biopsy? (Now Available) (ID 3253)
11:00 - 12:30 | Presenting Author(s): James Chih-Hsin Yang
- Abstract
- Presentation
Abstract
The discovery of specific mutations and associated addicted pathways in lung adenocarcinoma cells has led to the development of many targeted therapies useful for corresponding activating mutation. In addition, conventional chemotherapy and novel immunotherapy such as PD1/PDL1 antibodies are also very effective for lung cancer patients with or without specific driver mutation. Patients with metastatic lung cancer nowadays can be treated with multiple lines of effective treatment. Patients who receive more lines of therapy tend to live longer than those who had only receive limited number of treatment. In order to maximize the overall survival outcome of metastatic lung cancer patient who receives systemic treatment, it is important to find out the best first line choices and the best timing to change the treatment regimen to second line and so forth. Tumor reduction or stabilization by imaging criteria has been used widely for a long time in chemotherapy and targeted therapy era. RECIST (Response evaluation criteria in solid tumors) has been adopted as a uniform criteria for cancer clinical trial to classify the tumor response to certain treatment. However, in order to accommodate different cancer types and sites of metastasis, several variants of RECIST emerged to better evaluate the treatment response and necessity of maintain the present treatment. In daily practice, changes of tumor size in the image provide the best guidance for clinicians to continue or change regimen for the patients. In patients who has no reliable evaluable radiological image for follow up, such as patients who presented with effusion, bone metastasis, leptomeningeal metastasis or tumor with poor margin, patients’ clinical performance and alterations in tumor markers occasionally can provide clinicians information for judgement. The introduction of cell free plasma tumor DNA for the molecular diagnosis of cancer gave us a new change of how to manage the patients properly when changing regimen to prolong patients chance to survive or improving quality of life are attainable. There are a least 3 important applications for cell free tumor DNA detection. First is to provide information of specific mutation at the time of diagnosis or progression, so that a corresponding targeted therapy can be chosen as the best treatment of choice. Second is to use quantitative amount of specific mutation found in plasma cell free DNA to follow patient’s tumor. The presumption is the amount of specific mutation may represent the tumor load of the treated patients. The 3rd possible application is to use the novel mutations detected in the plasma at the time of diagnosis or during treatment follow up to select a theoretical best combination for patients. There are ample of analysis reported in the literature for the first and second possible applications of plasma cell free DNA. The evidence for the 3rd possible application is accumulating. However, there is no emphasis of using this vast information gathered in the plasma to guide the right timing to switch regimen. In addition, there has been a trend to continue original treatment in slow progressing patients beyond imaging progression, or to treat oligo-progressing sites with local irradiation or surgery in order to keep the original treatment. These approaches certainly will further complicate the rationale decision of right timing to change regimen. Thus, a few options exist for patients who are receiving targeted therapies. One is to use conventional ways of RECIST progression by imaging studies to change the treatment to further lines. The treatment outcome may be more predictable, because most of the clinical trials follow this dogma. A second choice is to treat patients beyond progression by RECIST and follow physicians judgment to switch the regimen. Several recent clinical trials use this criteria to change regimen and collect the treatment time as duration-of-treatment, or time-to-treatment-failure. The 3rd possible timing is to switch regimen according to plasma DNA alterations, for example, emergence of activating mutation when plasma tumor DNA was previously eradicated by current targeted therapy; add another targeted therapy when a new parallel pathways amplification is predicted from the plasma sample analysis. This strategy lack the support of prospective clinical trial data and was purely based on direct scientific deduction or instinct and a few case reports. Therefore, studies specifically designed to address the switch timing is very important. Unfortunately, the effort devoted to this area is lacking.
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ES18.03 - New Strategies to Overcome Resistance in EGFR Mutated NSCLC (Now Available) (ID 3254)
11:00 - 12:30 | Presenting Author(s): Paul A Bunn, Jr
- Abstract
- Presentation
Abstract
New Strategies to Overcome Resistance in EGFR Mutated NSCLC
Activating EGFR mutations occur in 15-50% of lung adenocarcinomas with a higher frequency in never or light smokers and individuals of East Asian origin. First and second generation EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib, afatinib and dacomitinib are associated with high response rates (50-75% and median progression free survival rates of 9-14 months. Failure in the CNS is frequent because these agents have poor CNS penetration and the most frequent cause of systemic failure is the development of T790M resistance mutations. Other reported mechanisms of resistance to first and second generation EGFR TKIs include small cell transformation, AXL overexpression, HER2 mutation and overexpression, Wnt pathway overexpression and other less common alterations. Standard platinum doublet chemotherapy is generally used for those with small cell transformation and these cases usually have Rb loss and p53 mutation. The addition of cetuximab to first or second generation EGFR TKIs did not appear to improve outcomes.
Osimertinib is a third generation EGFR TKI whose advantages include high sensitivity to both activating EGFR mutations and T790M mutations with lesser sensitivity to wild type EGFR. Osimertinib also crosses the blood brain barrier. A randomized phase III trial, AURA3, demonstrated that osimertinib was superior to chemotherapy and was associated with decreased CNS relapse in the second line setting after failure on a first generation EGFR TKI due to T790M.
These data with second line osimertinib led to a first line phase III randomized trial, FLAURA, comparing osimertinib to either gefitinib or erlotinib. Osimertinib was associated with a significantly longer PFS, a significantly longer time to CNS progression, a significantly longer duration of response and a longer overall survival that had not reached significance at most recent analysis. Patterns of resistance to first line osimertinib are only emerging now but include alterations that have specific targeted therapy such as MET amplification (15%), BRAF mutations (3%), HER2 amplification (1%), ALK fusions (1%), PI3K mutations (3%), KRAS mutations (2%), C797s or other resistance mutations (2%), SCLC transformation (5%), CDK and cell cycle alterations (2-5%). Because these have specific non-chemotherapy treatment options, NGS testing should be done on blood ctDNA and if negative on tissue at the time of progression.
For those without these actionable alterations, chemotherapy is the next standard therapy although combinations of chemotherapy with checkpoint inhibitors with or without anti-VEGF agents is under investigation due to a positive subset analysis of the IMPOWER 150 trial. The addition of checkpoint inhibitors to first line TKIs has proven to have increased toxicity with low activity.
Another way to delay or prevent resistance is to use combinations in the first line therapy. Combinations of EGFR TKIs with anti-VEGF therapies, with anti-MET therapies, with anti-EGFR antibodies, and with chemotherapy are in progress. Initial trials combining erlotinib with bevacizumab demonstrated improved PFS but not OS. Current trials are combining newer EGFR TKIs such as osimertinib with anti-VEGF antibodies such as bevacizumab or ramicirumab are in progress. Trials using anti-VEGFR TKIs are also in progress. Preclinical studies indicated that combining anti-EGFR antibodies such as cetuximab or necitumumab with EGFR TKIs could overcome some resistance led to other ongoing clinical trials combining these agents. Amplification of MET is a common mechanism of resistance to EGFR TKIs, so the combination of MET TKIs with EGFR TKIs is rational and trials are ongoing. Understanding the mechanisms by which EGFR mutant cells can persist in the presence of initial EGFR TKIs remains a priority for future investigation.
The adjuvant use of EGFR TKIs after surgical resection of early stage NSCLC patients with EGFR mutations has clearly established superiority in recurrence free survival but not in overall survival. It appears that there is insufficient cell kill to lead to an increase in the cure rate but additional survival based adjuvant trials such as ”ALCHEMIST” are ongoing.
Neoadjuvant studies could provide downstaging because the response rates are high. It is not clear whether this would be more likely to provide an increase in cure rates compared to adjuvant use of these agents. These neoadjuvant trials are providing surgical samples to explore mechanisms by which cells persist after EGFR TKI therapy. This incredibly important information could lead to rational combinations that could increase pCR rates in early stage patients and improved outcomes in advanced stage patients.
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ES18.04 - New Strategies to Overcome Resistance in ALK Rearranged NSCLC (Now Available) (ID 3255)
11:00 - 12:30 | Presenting Author(s): Sai-Hong Ignatius Ou
- Abstract
- Presentation
Abstract
Since the discovery of ALK+ NSCLC in 2007, there are now 6 ALK TKI have been approved or in clinical development. These 6 ALK TKI can be generally divided into 3 generations. First-generaion (Crizotinib). Second Generaion (Alectinib, Ceritinib, Brigatinib, Ensartinib). THrid-generation (Lorlatinib). The advantages of the second-generation ALK TKI or beyond is better potentcy an excellent improved CNS penetration. The mode of progression in ALK+ NSCLC are 4 fold and can be single or combination according to individaul patients: developed of acquired second site ALK mutations, CNS progression, bypass activation, and histological transformation.
For second site ALK mutations, sequencing ALK TKIs that will overcome the particular second site mutation(s) or proceed to the most potent ALK TKI is likley be successful.
For CNS progression, lorlatinib has demonstrated CNS activity in CNS progression from second generation ALK TKIs (ceritinib, alectinib). Additionally the use of stereotactic radiation (SRS) or whole brian radiation can contral CNS progression but clinicians should look out for radiation necrosis.
For second bypass activation such as (i.e. RAS, SRC, EGFR, Kit) in vritro pre-clinical modles of combining specific bypass inhibitor and ALK TKI were albe to inhibit growth of these resistance cell lines or patient dervied PDX model, clinical trials are on-going but to date clinical data are lacking. Additional the use of chemotherapy especailyl pemetrexed-based chemotherapy in addition to ALK TKI has showen to be more efficacious than just switching to chemotherapy while discontinuing ALK TKI
For histologic transformation most commonly small cell transformation, the switching to small cell regimen is only viable option at this point. The addition to immunotherapy to chemotherapy (e.g. IMpower133 regimen) or IO + IO combination (e.g. chckmate-032) should be explored in small cell tranformation as mode of progression in ALK+ NSCLC.
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Author of
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-01 - Major Therapeutic Response to T-DM1 in Metastatic Lung Adenocarcinoma with HER2 Mutation (Now Available) (ID 1105)
08:00 - 18:00 | Presenting Author(s): Matteo Giaj Levra
- Abstract
Background
The HER2 exon 20 mutation is described in 1-5% of patients with Non-small cell Lung cancer, and at the moment no targeted agents are approved in Europe. However, the use of conjugated antibodies such as trastuzumab and ado-trastuzumab emtansine (T-DM1) has shown promising results.
Method
We describe the case of a major response to T-DM1 in fourth line treatment in a patient with metastatic adenocarcinoma and HER2 mutation.
Result
A 60-year-old male, former smoker (3 packs/year), presented to the emergency room in 2016 for dyspnoea. A bilateral pleural and compressive pericardial effusion with tamponade requiring pericardial drainage were discovered. A lung adenocarcinoma with HER2 mutations was diagnosed. He benefited from two successive treatment lines between September 2016 and September 2017 (carboplatin- paclitaxel and bevacizumab followed by bevacizumab maintenance until progression, then pemetrexed for two cycles). At this time, he developed a new disease progression as a recurrence of tamponade requiring surgical drainage and a third line with docetaxel and trastuzumab was started for twelve cycles. After eight months, he presented an acute respiratory failure due to the recurrence of pericardial and pleural effusions, requiring a pleural drainage (Fig.1A). After discussion at the multidisciplinary meeting, a fourth line of treatment with T-DM1 in compassionate has been proposed. After three cycles, we observed an excellent clinical response, with disappearance of dyspnoea, resumption of normal daily activity. The radiological evolution was also very favourable (Fig.1B). The patient benefited from other six months of treatment before getting a new progression.
Conclusion
In this case T-DM1 showed a major clinical and radiological benefit despite its use in fourth line. Other clinical reports and phase II trials confirmed promising results with targeted agents already used in breast cancer. Several studies are exploring the efficacy of these agents, opening up new hopes.
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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): Matteo Giaj Levra
- 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 | Presenting Author(s): Matteo Giaj Levra
- 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.
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MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.02 - Durvalumab Impact in the Treatment Strategy of Stage III Non-Small Cell Lung Cancer (NSCLC): An EORTC Young Investigator Lung Cancer Group Survey (Now Available) (ID 608)
15:15 - 16:45 | Presenting Author(s): Matteo Giaj Levra
- Abstract
- Presentation
Background
Stage III NSCLC represents a very heterogeneous population with extremely different treatment modalities including surgery, chemotherapy (CT) and radiotherapy (RT), mostly in combination. The results of the PACIFIC trial have now been reported in full including an overall survival (OS) benefit with durvalumab in addition to concomitant CT-RT. An electronic European survey was circulated to evaluate the impact of durvalumab in the staging and treatment strategy of stage III disease.
Method
A Young Investigator EORTC Lung Cancer Group survey containing 31 questions, was distributed between 31/01/18 and 31/03/19 to EORTC LCG and several European thoracic oncology societies’ members
Result
206 responses were analyzed (radiation oncologist: 50% [n=103], pulmonologist: 26.7% [n=55], medical oncologist: 22.3% [n=46]; 81.5% with >5 years experience in treating NSCLC). Italy (27.7%, n=57), Netherlands (22.8%, n=47), France (13.6%, n=28), and Spain (11.6%, n=24) contributed most. 83.5% (n=172) confirmed that they had access to durvalumab at the time of the survey. 97.6% (n=201) report that treatment decision is made by a multidisciplinary board. Regarding staging, 76.7% (n=158) support the need of a mediastinal pathological staging in case of suspect lymph-nodes, with a preference for EBUS/EUS (61.2%, n=126). 81.6% (n=168) treated more than half of patients with a concomitant CT-RT with the 1st cycle of chemotherapy in 39.7% (n=81). 95.1% consider durvalumab as practice changing, especially given the OS results (77.9%, n=152/195). 30% (n=119/395) will give patients concomitant CT-RT if PD-L1 >1%, and in borderline resectable cases 17.7% (n=70/395) will propose concomitant CT-RT instead of surgery. Durvalumab administration will be given regardless of PDL1 status in 13.1% (n=27) and 28.6% (n=59) would consider the possibility of a rebiopsy after CT-RT in case of negative PD-L1. 38.8% (n=80) foresee some problems with PD-L1 testing in this population due to availability of cytologic or small histologic samples. About 53.8% (n=105/195) normally will start durvalumab within 6 weeks after CT-RT and 48.5% (n=100) would also use durvalumab after sequential CT-RT
Conclusion
Durvalumab results are changing the treatment approach to stage III unresectable (and maybe resectable) NSCLC and planned strict adherence to the patient population as recruited to the PACIFIC study, was not demonstrated. This survey was released after the EMA approval of durvalumab and PD-L1 status seems to play a role in the treatment strategies, but surprisingly almost half of the clinicians will use durvalumab after sequential CT-RT without safety or efficacy data.
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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): Matteo Giaj Levra
- 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.
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P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.18-10 - Importance of the Multidisciplinary Tumor Board in the Treatment Strategy of Stage III Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 1107)
10:15 - 18:15 | Author(s): Matteo Giaj Levra
- Abstract
Background
Stage III Non-Small Cell Lung Cancer (NSCLC) represents a heterogeneous population with different treatment strategies, often in combination. The PACIFIC trial is changing practices. It is therefore necessary to evaluate our current practices in order to identify the patients that should most likely receive this treatment after chemoradiotherapy
Method
A database constructed from our weekly multidisciplinary thoracic oncology meetings was retrospectively screened from 01/2010 to 01/2017. Consecutive patients with stages III NSCLC were included. We aimed to describe proposed treatment strategies and those really performed
Result
Of the 411 patients studied, 249 had a stage IIIA NSCLC and 162 a stage IIIB NSCLC. Median age was 65 years [IQR 25%-75%, 58-72], 309 (75%) patients were male. The majority of the patients (n=270, 69%, 20 missing data) had an ECOG-Performance status of 0 or 1. Regarding histology, 199 (48%) patients had an adenocarcinoma and 199 (48%) a squamous cell carcinoma. Treatment strategies are described in Table 1. Sixty-nine (17%) patients received exclusive chemoradiotherapy, and 60 (15%) were planned for neoadjuvant chemotherapy for subsequent surgery. Among these 60 patients, after the first cycles of the initial chemotherapy, only 37 (62%) received surgery in accordance with the multidisciplinary meeting decision; 6 (10%) received concurrent chemoradiotherapy and 6 (10%) sequential chemoradiotherapy.
Conclusion
In our cohort, 8% (32/411) of the stage III patients benefited from a chemoradiotherapy upfront. According to the PACIFIC study, these patients could receive adjuvant immunotherapy. We could ask if the patients planned for surgery after neoadjuvant chemotherapy should not be initially proposed for a concurrent chemoradiotherapy to give them the opportunity to receive adjuvant immunotherapy. Survival analyses according to treatment strategy are ongoing
