Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
were estimated using the Kaplan–Meier method. Results: Between October
2012 and December 2015, 34 ALK-positive patients with locally advanced or
metastatic NSCLC were treated with crizotinib, 31 of them after the first-line
chemotherapy. Characteristics of patients: median age, years (range): 58 (23-
77), ECOG/WHO PS: 0, 1, 2, 3 in 1, 23, 6, and 4 patients, respectively. Histology:
adenocarcinoma in 33 cases, NSCLC, NOS in one. Patients with locally
advanced disease: 2, with metastatic disease: 32. Median PFS was 18 months
(95%CI: 13 - 22), median OS (number of events: 13, 38,24%): 32 months (95%CI:
18 - 32), response rates: CR + PR: 3 + 23, 76,5% (95%CI 50-100%), SD: 7, 21,5%,
PD: 3, 8,8%, not stated: 1. There was a signifcant improvement in PS within
2 month, mean difference: - 0,62, p = 0,0025. Grade 3/4 toxicities occurred
in 15/2 patients. Crizotinib was permanently discontinued due to AEs in 2
patients only. PFS and OS in our study were numerically better in comparison
with PROFILE 1007. On the other hand, common grade 3 toxicities occured also
more often. Conclusion: Conclusion: Our study provides real-world evidence of
the efficacy of crizotinib in patients with ALK-positive NSCLC, treated outside
of clinical trials.
Keywords: crizotinib, response, survival, NSCLC
POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
ALK CLINICAL –
WEDNESDAY, DECEMBER 7, 2016
P3.02A-027 A RETROSPECTIVE ANALYSIS OF THE EFFICACY AND
SAFETY OF ALK INHIBITORS IN ALK-POSITIVE LUNG CANCER
PATIENTS
Kazutoshi Komiya 1 , Tomomi Nakamura 2 , Yuki Kurihara 1 , Haruki Hirakawa 1 ,
Hironori Sadamatsu 3 , Chiho Nakashima 1 , Hitomi Umeguchi 3 , Yuji Takeda 1 ,
Shinya Kimura 1 , Naoko Sueoka-Aragane 1
1 Saga University, Saga/Japan, 2 Internal Medicine, Saga University, Saga/Japan,
3 Japanese Red Cross Karatsu Hospital, Saga/Japan
Background: Patients with non-small cell lung cancer (NSCLC) harboring ALK
rearrangements have been shown to exhibit a good response to ALK-inhibitor
treatment. However, serious adverse events are observed in some patients.
Therefore, it is important to precisely evaluate severity of adverse events
and treat properly. Methods: We performed a retrospective study of the
efficacy and safety of ALK inhibitors in ALK-positive lung cancer patients.
Between September 2013 and April 2016, 9 patients receiving ALK inhibitors
in our department were analyzed. All patients gave informed consent for the
use of their clinical data. Results: The median age was 67 years (range, 54-74
years), and the histological type of cancer was adenocarcinoma in all cases.
One patient had stage IIIB, four patients had stage IV and four patients had
postoperative recurrence. Seven cases were fluorescence in situ hybridization
(FISH) positive / immunohistochemistry (IHC) positive, and two cases were
FISH positive / IHC negative. Crizotinib and alectinib were administered orally
to seven and eight patients, respectively. In evaluable cases, the disease
control rate was more than 80% both crizotinib and alectinib. The median
progression-free survival was longer in alectinib treatment than in crizotinib
treatment (133 days (range, 8-635 days) vs 51 days (range, 3-452 days)). Among
7 patients received crizotinib, the adverse events included grade 4 increased
ALT and AST levels in 1, grade 3 pneumonitis in 2, grade 2 edema in 1, and
grade 2 increased creatinine level in 1. Among 8 patients received alectinib,
the adverse events were included grade 2 pneumonitis in 2 and grade 2 skin
disorder (drug eruption) in 1. Severe adverse events such as pneumonitis and
liver dysfunction were observed within 40 days, and in these cases, treatment
could not be continued. Visual disorder, gastrointestinal symptoms such
as nausea, vomiting and constipation were more frequent in crizotinib
treatment, but these symptoms were reduced by switching from crizotinib to
alectinib. Drug discontinuation rate because of adverse events was higher in
crizotinib treatment than in alectinib treatment (71% vs 50%). No treatmentrelated
death occurred. Conclusion: Although ALK inhibitors have therapeutic
effect against ALK-positive NSCLCs, severe adverse events occur in some
patients. Based on these adverse events as well as the efficacy in each agent,
alectinib treatment may be recommended in first line setting for ALK-positive
NSCLC patients.
Keywords: ALK-positive lung cancer, ALK inhibitors, non-small cell lung cancer,
retrospective study
POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
ALK CLINICAL –
WEDNESDAY, DECEMBER 7, 2016
P3.02A-028 ANAPLASTIC LYMPHOMA KINASE FUSION ONCOGENE
POSITIVE NON-SMALL CELL LUNG CANCER - THE EXPERIENCE OF
AN INSTITUTION
Sérgio Azevedo, Li Bei, Joana Cunha, Cristina Oliveira, Ana Rodrigues, Inés
Pousa, Isabel Azevedo, Júlio Oliveira, Marta Soares
Medical Oncology, Instituto Português de Oncologia Do Porto Francisco Gentil,
Epe, Porto, Portugal, Porto/Portugal
Background: Approximately 3–7% of lung tumors harbor Anaplastic
Lymphoma Kinase (ALK) fusions. The aim of the current study was to
characterize the population of patients with ALK positive non small cell
lung cancer (NSCLC) treated at our Institution. Methods: Retrospective
analysis of 26 ALK positive NSCLC, diagnosed between December/2008 and
February/2016. Eligible patients had lung adenocarcinoma harboring ALK
translocation according to fluorescent in situ hybridization. Best response
was assessed using RECIST (version 1.1). Results: Twenty six patient cases are
reported, diagnosed between 01/12/2008 and 29/02/2016. Median age was
56 years, 60.7% of patients were women, and 71.4% were never-smokers.
Twenty-four (92.3%) were adenocarcinomas. All patients were EGFR negative.
Twenty (76.9%) were stage IV. Fifteen patients (57.7%) were treated in first
line with palliative chemotherapy (CT), thirteen of them with platinum/
pemetrexed. Twelve patients (46.1%) were treated with crizotinib, two in first
line, nine in second line and one in third line; one patient was treated with
ceritinib in fourth line. As major adverse events there were eight cases (30.7%)
of venous thromboembolism, including five (19.2%) pulmonary embolisms.
ALK directed therapy, namely crizotinib, was safe and well-tolerated. Most of
the patients (91.7%) were treated with the standard dose of 250mg twice per
day. One patient needed dose reduction due to hepatotoxicity (G3, CTCAE.V4).
The most frequent treatment-related adverse events were emesis (G1) vision
disorders (G1), and increased AST/ALT (G3). Three patients treated with CT
had grade 3 toxicity (pneumonia with respiratory failure, anemia, peripheral
neuropathy). Median follow-up of study population was 13.5 months. In
patients treated with crizotinib objective response rate (ORR = complete
response + partial response) was 50% and clinical benefit (CB = complete
response + partial response + stable disease) was 75%. In patients treated
with CT ORR was 6.7% and CB was 73%. Seven (26.9%) patients died during
the study period. Median overall survival has not been reached. Conclusion:
ALK directed therapy provided increased benefit and lower toxicity compared
to CT. During the study period, there were several treatment guidelines
updates impacting the patient’s management. Presented results are
consistent with the published literature.
Keywords: Non-small cell lung cancer, Adenocarcinoma, Anaplastic lymphoma
kinase, Crizotinib
POSTER SESSION 3 – P3.02a: ADVANCED NSCLC & CHEMO-
THERAPY/TARGETED THERAPY/IMMUNOTHERAPY
ROS1 –
WEDNESDAY, DECEMBER 7, 2016
P3.02A-029 PATIENTS WITH ROS1 REARRANGEMENT POSITIVE
NON-SMALL CELL LUNG CANCER BENEFIT FROM PEMETREXED-
BASED CHEMOTHERAPY
Zhengbo Song 1 , Yiping Zhang 2 , Xinmin Yu 1
1 Medical Oncology, Zhejiang Cancer Hospital, Hangzhou/China, 2 Zhejiang Cancer
Hospital, Hangzhou/China
Background: ROS1 gene-rearrangement in non-small cell lung cancer (NSCLC)
patients has recently been identified as a driver gene and benefited from
crizotinib treatment. However, no data is available for ROS1-positivity NSCLC
about chemotherapeutic options and prognostic data. We investigated
pemetrexed-based treatment efficacy in ROS1 translocation NSCLC patients
and determined the expression of thymidylate synthetase (TS) to provide a
rationale for the efficacy results. Methods: We determined the ROS1 status
of 1750 patients with lung adenocarcinoma. Patients’ clinical and therapeutic
profile were assessed. In positive cases, thymidylate synthetase (TS) mRNA
level was performed by RT-PCR. For comparison, we evaluated the TS mRNA
status and pemetrexed-based treatment efficacy from 170 NSCLC patients
with anaplastic lymphoma kinase (ALK) translocation (n=46), EGFR mutation
(n=50), KRAS mutation (n=32) and wild-type of EGFR/ALK/ROS1/KRAS (n
= 42). Results: Thirty-four ROS1 translocation patients were identified at
two institutions. Among the 34 patients, twelve with advanced stage or
recurrence were treated with pemetrexed-based first-line chemotherapy.
The median progression-free survivals of pemetrexed-based first-line
chemotherapy in ROS1 translocation, ALK translocation, EGFR mutation,
KRAS mutation and EGFR/ALK/ROS1/KRAS wild-type patients were 6.8, 6.7,
5.2, 4.2 and 4.5 months, respectively (P=0.003). The TS mRNA level was lower
in patients with ROS1-positive than ROS1-negative patients (264±469×10 -4 vs.
469 ± 615×10 -4 , P=0.03), but similar with ALK-positive patients (264±469×10-
4 vs. 317±524×10 -4 , P=0.64). Conclusion: Patients diagnosed with ROS1
Copyright © 2016 by the International Association for the Study of Lung Cancer
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