Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
(EGFR-TKI) drastically prolonged progression free survival (PFS) of patients
with non-squamous non-small-cell lung cancer (NSCLC) harboring EGFR
mutations. However, most cases show tumor regrowth after approximately
only ten months treatment, and the prognosis is still poor. Then it is necessary
to make new strategy of treatment for NSCLC harboring EGFR mutation,
and we designed phase I/II study of Erlotinib, Carboplatin, Pemetrexed
and Bevacizumab in chemotherapy-naïve patients with EGFR mutation
positive advanced non-squamous NSCLC. Methods: In the phase I part,
eligible patients were administrated orally Erlotinib daily, and Pemetrexed,
Carboplatin and Bevacizumab intravenously every three weeks for four
cycles with maintenance of Pemetrexed and Bevacizumab until PD. The dose
level of Erlotinib were 100mg in level 1 and 150mg in level 2. And the dose of
pemetrexed, carboplatin and bevacizmab were fixed as 500mg per m 2 , AUC6
and 15mg per kg. The dose limiting toxicities are Grade (Gr) 3-4 neutropenia
with fever or infection, Gr 4 leukopenia lasting for 7 days or longer, Gr 4
thrombocytopenia, Gr 3-4 uncontrollable non-hematological toxicity and
delayed administration of the subsequent course by more than 2 weeks due
to adverse events. Results: Six patients were enrolled in Phase I part (level
1-three, level 2-three). The median age was 71.5 y.o. (Range, 46-76 y.o). Male
was one and female were five. Histology of all patients was adenocarcinoma,
and Ex19del was four and Ex21 L858R was two. A Gr3 of neutropenia without
fever was observed in level 1, and a Gr3 of neutropenia without fever, three
Gr3 thrombocytopenia and a stomatitis were observed in level 2(Table1). No
DLT events were observed in Phase I. Table1
Grade 1 2 3
ANC 1 1
PLT 2
Anemia 2
Whereas the T790M mutation confers prolonged survival and sensitivity
to 3rd generation TKIs, there is no data on outcome and treatment of
MET-driven resistant EGFR-mutated NSCLC patients. Methods: Molecular
and clinico-pathological data from patients with advanced EGFR-mutated
NSCLC and MET overexpression or amplification on a post-progression
(PP) sample obtained after treatment with EGFR TKI were retrospectively
reviewed in 15 nationwide centers. MET overexpression was defined by MET
immunochemistry (IHC) score 3+ and MET amplification was assessed by FISH
and defined by MET/CEP7 ratio >2 or MET copy number >6 or MET clusters.
Results: 43 patients were included (24 del19, 16 L858R and 3 rare EGFR
mutations). The median time between EGFR TKI initiation and PP biopsy was
13.8 months [2.1-61.3]. On PP biopsy, 20 tumors tested for FISH (53%) had
MET amplification and all out of 37 samples tested for IHC were scored 3+. No
epithelial to mesenchymal transformation was observed. A T790M mutation
was found in 12/42 (29%) PP biopsies. 5 patients had both MET amplification
and T790M mutation. The median overall survival (OS), and the median PP
OS were 36.2 months [IC95% 27.3-45.6] and 18.5 months [IC95% 10.6-26.5],
respectively. 16 patients received a MET TKI. Objective response was reported
in 1 out of 12 evaluable patients treated with a MET TKI as single agent and in 1
of 2 patients treated with a combination of MET and EGFR TKIs. No significant
difference was found according to the MET FISH status for OS and PP OS. 3
out of 9 evaluable T790M-positive patients had an objective response upon
3rd generation EGFR TKI. T790M-positive patients had a better OS (median
84.7 vs. 32.2 months, p=0.016) and PP OS (median 36.9 vs. 11 months, p=0.0141)
than T790M-negative patients. Conclusion: Even when associated with METdriven
resistance to EGFR TKIs, the T790M mutation may be associated with
relative sensitivity to 3rd generation EGFR TKIs and prolonged survival. MET
TKIs alone yield low ORR, which emphasizes the need for further evaluation of
combinations of EGFR and MET TKIs.
Keywords: MET amplification, non-small cell lung cancer, EGFR mutation, TKI
resistance
Stomatitis 1 1
Nausea 1 2
Appetite loss 1 2
Rash 1
Transaminase 1
T.Bil 1
Fatigue 1
Bleeding 1
Diarrhea 1
Conclusion: The recommend dose of Erlotinb is 150mg daily.
Keywords: EGFR, Erlotinib, bevacizumab, pemetrexed
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR CLINICAL –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-051 OUTCOME OF ADVANCED EGFR-MUTATED NSCLC
PATIENTS WITH MET-DRIVEN ACQUIRED RESISTANCE TO EGFR TKI.
RESULTS OF THE METEORE STUDY
Simon Baldacci 1 , Julien Mazieres 2 , Pascale Tomasini 3 , Nicolas Girard 4 , Florian
Guisier 5 , Clarisse Audigier Valette 6 , Isabelle Monnet 7 , Marie Wislez 8 , Maurice
Pérol 9 , Pascal Dô 10 , Eric Dansin 11 , Charlotte Leduc 12 , Etienne Giroux Leprieur 13 ,
Denis Moro-Sibilot 14 , Zoulika Kherrouche 15 , Julien Labreuche 16 , Alexis Cortot 1
1 Service de Pneumologi Et Oncologie Thoracique, CHU Lille, Univ. Lille, Lille/France,
2 Toulouse University Hospital, Toulouse/France, 3 Department of Multidisciplinary
Oncology and Therapeutic Innovations, Assistance Publique-Hôpitaux de Marseille,
Marseilles/France, 4 Respiratory Medicine, Thoracic Oncology, Louis Pradel
Hospital, Hospices Civils de Lyon, Lyon/France, 5 Rouen University Hospital, Rouen/
France, 6 Centre Hospitalier Sainte Musse, Toulon/France, 7 Centre Hospitalier
Intercommunal de Creteil, Creteil/France, 8 Service de Pneumologie, Aphp Hôpital
Tenon, Paris/France, 9 Groupe Thoracique Et Orl, Centre Léon Bérard, Lyon/France,
10 Centre Régional de Lutte Contre Le Cancer François Baclesse, Caen/France,
11 Centre Oscar Lambret, Lille/France, 12 CHU Strasbourg, Strasbourg/France, 13 Aphp
– Hôpital Ambroise Paré, Boulogne-Billancourt/France, 14 Pôle Thorax Et Vaisseaux,
Unité D’Oncologie Thoracique, Service de Pneumologie, Grenoble/France, 15 Cnrs
Umr 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille,
Lille/France, 16 Ea 2694 Université de Lille, Lille/France
POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
EGFR CLINICAL –
WEDNESDAY, DECEMBER 7, 2016
P3.02B-052 AFATINIB WITH OR WITHOUT CETUXIMAB FOR FIRST-
LINE TREATMENT OF EGFR-MUTANT NSCLC: INTERIM SAFETY
RESULTS OF SWOG S1403
Sarah Goldberg 1 , James Moon 2 , Rogerio Lilenbaum 1 , Katerina Politi 1 , Mary
Ann Melnick 1 , Thomas Stinchcombe 3 , Leora Horn 4 , Everett Chen 5 , Jieling
Miao 2 , Mary Redman 2 , Karen Kelly 6 , David R. Gandara 7
1 Yale School of Medicine, New Haven/CT/United States of America, 2 Swog
Statistical Center, Seattle/WA/United States of America, 3 Duke University,
Durham/NC/United States of America, 4 Vanderbilt Ingram Cancer Center, Nashville/
TN/United States of America, 5 Kaiser Permanente Medical Group, Bellflower/CA/
United States of America, 6 Hematology Oncology, UC Davis Comprehensive Cancer
Center, Sacramento/CA/United States of America, 7 Division of Hem-Oncology, UC
Davis Comprehensive Cancer Center, Sacramento/CA/United States of America
Background: Afatinib is used as first-line therapy for EGFR-mutant non-small
cell lung cancer (NSCLC), however resistance invariably develops. To attempt
to delay resistance and improve survival, we are conducting a randomized
Phase II/III trial of afatinib plus cetuximab versus afatinib alone in treatmentnaïve
patients with advanced EGFR-mutant NSCLC (NCT02438722). Methods:
Previously untreated patients with EGFR exon 19 deletion or L858R point
mutation are randomized to afatinib 40mg PO daily plus cetuximab 500mg/
m2 IV every 2 weeks (afat/cetux) or afatinib 40mg PO daily (afat). Dose
reductions are performed for grade 3-4 or intolerable or medically concerning
grade 2 adverse events (AEs) per CTCAE v4.0. The Phase II primary endpoint is
progression-free survival and the Phase III primary endpoint is overall survival.
Here we review the safety data after enrollment of the first 53 patients.
Results: 53 patients were registered as of June 30, 2016, and safety has been
assessed in 47 (23 treated with afat/cetux and 24 with afat, see Table). Grade
1-2 rash occurred in 71% of patients receiving afat/cetux and 63% of patients
on afat. Grade 3 rash was noted in 22% of patients on afat/cetux. Fatigue was
more common in the combination arm; all occurrences were grade 1-2. Grade
1-2 diarrhea and other gastrointestinal AEs were comparable between the
two arms. There were similar numbers of dose reductions for AEs on each arm.
Three patients discontinued treatment due to AEs: 2 on the afat/cetux arm
due to hyperglycemia and accumulated side effects and 1 on the afat arm due
to weight loss and diarrhea.
Background: Several mechanisms of acquired resistance to EGFR TKIs have
been described including the T790M mutation and MET amplification.
S640 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017