Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Yasir Elamin 1 , Waree Rinsurongkawong 2 , Hai Tran 3 , Kathryn Gold 4 , Jeff Lewis 2 ,
Emily Roarty 5 , Andrew Futreal 6 , Jianjun Zhang 7 , John Heymach 8
1 Thoracic/head and Neck Medical Oncology, MD Anderson Cancer Center, Houston/
TX/United States of America, 2 MD Anderson Cancer Center, Houston/TX/United
States of America, 3 Thoracic/head and Neck Medical Oncology, MD Anderson
Cancer Center, Houston/United States of America, 4 Moores Cancer Center,
University of California San Diego, La Jolla/United States of America, 5 Thoracic,
Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer
Center, Houston/TX/United States of America, 6 The University of Texas MD
Anderson Cancer Center, Houston, Hx/United States of America, 7 Department of
Thoracic/head and Neck Medical Oncology, The University of Texas MD Anderson
Cancer Center, Houston/AL/United States of America, 8 Thoracic/head and Neck
Medical Oncology, MD Anderson, Houston/TX/United States of America
Background: EGFR mutations define a distinct subset of NSCLC characterized
by clinical benefit from tyrosine kinase inhibitors. The impact of genomic
alterations that coexist with EGFR mutations is not fully understood. In
addition, the responsiveness of EGFR mutant NSCLC to immune checkpoint
blockade is not well defined. Methods: We queried our prospectively collected
MD Anderson Lung Cancer Moon Shot GEMINI Database to identify EGFR
mutant NSCLC patients. We analyzed the genomic landscape of these tumors
derived from next generation sequencing, performed as part of routine
clinical care, to comprehensively describe the concurrent genomic aberrations
in EGFR mutant NSCLC and their impact on clinical outcomes. We used log
rank and Fisher’s exact tests to identify associations between co-concurrent
mutations and clinical outcomes. Results: 1958 non-squamous NSCLC
patients were identified in the GEMINI database. The frequency of EGFR
mutations was 14.1% (n=276). Among EGFR mutant patients, 188 underwent
targeted next generation sequencing of a minimum of 46 cancer related
genes. The majority of EGFR mutant patients (77.6%, n=146) had at least one
coexisting mutation. The most frequent co-mutations identified were TP53
(47%, n=88), CTNNB1 (7.5%, n= 14) and PIK3CA (6.5%, n=12). ALK and ROS1
translocations were found to coexist with EGFR mutations in one patient
each. Of patients treated with a first or second generation TKI, concurrent
TP53 mutations were associated with a shorter progression free survival (HR=
1.81, P= 0.039). Eight patients with EGFR/CTNNB1 co-mutations developed
acquired TKI resistance with T790M secondary mutation being the resistance
mechanism in six (75%) of them suggesting that coexisting mutation can
dictate emerging resistance mechanisms. Twenty patients were treated with
anti PD1/PD-L1 agents (nivolumab n= 18, pembrolizumab n=2). Only two (10%)
patients achieved confirmed radiological response, one lasting for 6 months
and the second ongoing at 6 months. Both patients were never smokers, one
with EGFR exon 20 insertion and no concurrent mutations, and the other
with EGFR exon 19 deletion and TP53 mutation. Sixteen patients developed
confirmed progressive disease. Finally, one patient with 17 pack-year smoking
history, EGFR G719/S768I double mutation and concurrent PIK3CA mutation
achieved stable disease lasting for four months. The median progression free
survival for the cohort treated with immunotherapy was 2 months (range:
1-not reached). Conclusion: Concurrent genomic aberrations may predict
response duration to TKIs and may be associated with particular emerging
resistance mechanisms to TKIs in EGFR mutant NSCLC. Immunotherapy
results in durable clinical benefit in a subset of EGFR mutant NSCLC patients.
Keywords: Targeted therapy, Immunotherapy, EGFR mutant NSCLC
MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
MA14.05 IMPLICATIONS OF IMPLEMENTATION OF A PD-L1
BIOMARKER-BASED STRATEGY FOR TREATMENT OF ADVANCED
NSCLC
Min Huang 1 , James Pellissier 1 , Thomas Burke 2 , Ruifeng Xu 1
1 Center for Observational and Real-World Evidence, Merck & Co., Inc, North Wales/
PA/United States of America, 2 Center for Observational and Real-World Evidence,
Merck & Co., Inc., Lebanon/NJ/United States of America
Background: The KEYNOTE-010 (KN010) clinical trial, a multi-center,
worldwide, randomized Phase II/III trial of pembrolizumab 2m/kg every 3
weeks and docetaxel 75mg/m2 every 3 weeks in patients with previously
treated advanced NSCLC with PD-L1 positive tumors showed a significant
overall survival (OS) advantage for patients receiving pembrolizumab. We
examined the improvement in prognoses for patients who elect to learn their
PD-L1 biomarker results using extrapolative survival modeling. Methods:
Partitioned survival models to project long-term outcomes were developed
using data from patients enrolled in KN010, with treated patients in the
pembrolizumab 2m/kg and docetaxel 75mg/m2 arms included in these
analyses. As OS for docetaxel patients is not dependent on PD-L1 status,
KN010 results were assumed to represent docetaxel efficacy in all patients
irrespective of PD-L1 status.The model projected expected lifetime using
Kaplan Meier estimates of PFS and OS from the trial with extrapolation
based on parametric functions and long term registry data. Results: Results
directly from KN010 showed for patients with TPS≥50%, median survival
to be 8.2 months (6.4, 10.7) and 14.9 months (10.4, NA) for docetaxel and
pembrolizumab, respectively (HR= 0.54 (0.38, 0.77)). Model-based projections
show that should all patients be treated with docetaxel, expected mean
lifetime is 1.0 years. For patients receiving a PD-L1 biomarker test per KN010
28.49% will be identified as PD-L1 strong positive (TPS≥50%). PD-L1 (TPS
≥50%) predicts a life expectancy with biomarker directed pembrolizumab of
2.25 years on average. Conclusion: Use of PD-L1 biomarker identification can
significantly improve OS prognoses for patients considering pembrolizumab
and docetaxel with advanced NSCLC based on both clinical trial results and
model-based projections from KN010.
Keywords: PD-L1
MA14: IMMUNOTHERAPY IN ADVANCED NSCLC: BIOMARKERS AND COSTS
TUESDAY, DECEMBER 6, 2016 - 16:00-17:30
MA14.06 NIVOLUMAB IN NEVER SMOKER PATIENTS WITH
ADVANCED SQUAMOUS NSCLC: RESULTS FROM THE ITALIAN
EXPANDED ACCESS PROGRAMME (EAP)
Giuseppe Lo Russo 1 , Lucio Crinò 2 , Domenico Galetta 3 , Andrea Ardizzoni 4 ,
Enrico Cortesi 5 , Frederico Cappuzzo 6 , Paola Bordi 7 , Luana Calabrò 8 , Fausto
Barbieri 9 , Antonio Santo 10 , Giuseppe Altavilla 11 , Giacomo Cartenì 12 , Enrico
Mini 13 , Enrico Vasile 14 , Floriana Morgillo 15 , Alessandro Scoppola 16 , Carmelo
Bengala 17 , Gianpiero Fasola 18 , Natale Tedde 19 , Francovito Piantedosi 20
1 Fondazione IRCCS - Istituto Nazionale Dei Tumori, Milano/Italy, 2 Division of
Medical Oncology, Santa Maria Della Misericordia Hospital, Perugia/Italy,
3 National Cancer Research Centre, Istituto Tumori “Giovanni Paolo Ii” Bari, Italy,
Bari/Italy, 4 Medical Oncology, S. Orsola-Malpighi University Hospital, Bologna/
Italy, 5 Sapienza University, Rome/Italy, 6 Ausl Romagna, Ospedale Santa Maria
Delle Croci, Department of Oncology and Hematology, Ravenna/Italy, 7 Medical
Oncology Unit, University Hospital of Parma, Parma/Italy, 8 Medical Oncology
and Immunotherapy, University Hospital of Siena, Siena/Italy, 9 University
Hospital Policlinico of Modena, Oncology Unit, Modena/Italy, 10 Givop (Gruppo
Interdisciplinare Veronese Oncologia Polmonare), Azienda Ospedaliera
Universitaria Integrata Di Verona, Verona/Italy, 11 Department of Human Pathology,
Oncology Unit, University of Messina, Messina/Italy, 12 Division of Medical
Oncology, A.Cardarelli General Hospital, Napoli/Italy, 13 University of Florence,
Department of Experimental and Clinical Medicine, Firenze/Italy, 14 Azienda
Ospedaliero Universitaria Pisana Istituto Toscano Tumori, Pisa/Italy, 15 Oncologia
Medica, Dipartimento Di Internistica Clinica E Sperimentale “f. Magrassi E A.
Lanzara”, Seconda Università Degli Studi Di Napoli, Napoli/Italy, 16 Divisione Di
Oncologia, Idi-IRCCS, Roma/Italy, 17 Division of Medical Oncology, Misericordia
General Hospital, Grosseto/Italy, 18 Department of Medical Oncology, University-
Hospital Santa Maria Delle Grazie, Udine/Italy, 19 Oncologia Medica Asl2, Olbia/
Italy, 20 Department of Medical-Surgical Oncology and Thoracic Disease, Napoli/
Italy
Background: Nivolumab is the first checkpoint inhibitor approved for the
treatment of Sq-NSCLC to show a survival benefit vs the standard of care
docetaxel in the randomised, phase III, CheckMate 017 study. In the nivolumab
development program, a greater clinical benefit was shown in current and
former smokers than in never smokers. Nevertheless, no data are available in
this respect from a real world setting. For this reason, we decided to use the
data collected in the EAP in order to assess the effectiveness and tolerability
of nivolumab treatment in the never smoker patient population. Methods:
Nivolumab was provided upon physician request for patients aged ≥18 years
who had relapsed after a minimum of one prior systemic treatment for stage
IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously
every 2 weeks for