Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
MONDAY, DECEMBER 5, 2016
P1.07-003 A PHASE II STUDY EVALUATING THE COMBINATION
OF EVEROLIMUS WITH CARBOPLATIN/PACLITAXEL AS 1ST LINE
TREATMENT IN PATIENTS WITH ADVANCED LCNEC
Christian Grohé 1 , Walburga Engel-Riedel 2 , Cornelia Kropf-Sanchen 3 , Von
Pawel Joachim 4 , Sylvia Gütz 5 , Jens Kollmeier 6 , Wilfried Eberhardt 7 , Petros
Christopoulos 8 , Inko Nimmrich 9 , Christian Sieder 9 , Volker Baum 9 , Monika
Serke 10 , Michael Thomas 8
1 Evangelische Lungenklinik, Berlin/Germany, 2 Lungenklinik Köln-Merheim, Kliniken
Der Stadt Köln, Köln/Germany, 3 University Hospital Ulm, Ulm/Germany, 4 Klinik Für
Pneumologie, Asklepios Fachklinik München-Gauting, Gauting/Germany, 5 Kliniken
Für Pneumologie Und Kardiologie, Diakonissenkrankenhaus Leipzig, Leipzig/
Germany, 6 Lungenklinik Heckeshorn, Helios Klinikum Emil Von Behring, Berlin/
Germany, 7 Department of Medical Oncology, University Hospital Essen, Essen/
Germany, 8 Translational Lung Research Centre Heidelberg, Member of the German
Centre for Lung Research, Thoraxklinik Heidelberg, Heidelberg/Germany, 9 Business
Unit Oncology, Novartis Pharma GmbH, Nuremberg/Germany, 10 Lungenklinik
Hemer, Hemer/Germany
Background: Approximately 3% of all lung cancers are made up of large cell
neuroendocrine carcinoma of the lung (LCNEC). These tumors in general
have a bad prognosis and currently there are only very limited treatment
options, including platinum derivatives and etoposide. The PI3/AKT/mTOR
pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since
the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness
in different types of NETs, we tested whether everolimus might be also an
effective treatment option in advanced LCNEC patients. Methods: In this
multi-center, open-label, phase II study, everolimus was combined with
platin-based chemotherapy in patients with histologically confirmed stage IV
LCNEC according to WHO criteria. Further inclusion criteria were measurable
disease according to RECIST 1.1 and adequate bone marrow, renal, and liver
function. Main exclusion criteria were symptomatic CNS metastases and
prior treatment for advanced LCNEC. Enrolled patients received everolimus
once a day in combination with 4 cycles of carboplatin and paclitaxel,
followed by daily everolimus maintenance therapy. The primary objective
was to evaluate the efficacy by assessing the proportion of progression-free
patients after three months of treatment. Results: Ten German trial sites
enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary
endpoint (proportion of pts progression-free at month 3) was achieved by
24 patients (49%), assessed by an independent central imaging reviewer.
Further efficacy evaluation showed an overall response rate (ORR) until
month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median
progression-free survival (PFS) of 4.3 months, and a median overall survival
(OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled
patients with grade 3/4 toxicities in 51%. Most frequent toxicities were
diarrhea, fatigue, anemia, and neutropenia. Conclusion: The results show that
a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor
everolimus is an alternative treatment option for LCNEC patients. When
comparing to other trials, the effectiveness is comparable to a treatment
regimen of cisplatin and etoposide.
Keywords: LCNEC, Neuroendocrine tumor, Everolimus
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
MONDAY, DECEMBER 5, 2016
P1.07-004 UPDATED ANALYSIS OF PHASE II STUDY OF HA-
IRINOTECAN, A CD44-TARGETING FORMULATION OF HYALURONIC
ACID AND IRINOTECAN, IN SMALL CELL LUNG CANCER
Muhammad Alamgeer 1 , Peter Briggs 1 , Ben Markman 1 , Peter Midolo 1 , Neil
Watkins 2 , Beena Kumar 3 , Vinod Ganju 1
1 Medical Oncology, Monash Cancer Centre, East Bentleigh/Australia, 2 The Kinghorn
Cancer Centre, Garvan Institute of Medical Research, Darlinghurst/NSW/Australia,
3 Anatomical Pathology, Monash Medical Centre, Clayton/Australia
Background: Preclinical studies in small cell lung cancer cell (SCLC) have
shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan
and selectively decrease CD44 expressing (stem cell-like) tumour cells. The
current “proof of principle” study was aimed to replicate these findings by
investigating the effect on clinical outcome according to CD44 expression.
Final efficacy and bio-marker data on the study is presented. Methods:
Patients with ESLC, having measurable disease, suitable for safe biopsy and
able to give informed consent were screened for this study. First 5 patients
were treated with HA-irinotecan (150mg/m 2 ) and carboplatin (AUC 5), every
3 weeks to evaluate safety data. Subsequent patients were stratified as first
line or second line. All second line patients receive open label HA-irinotecan,
while first line patients are randomized to receive either HA-irinotecan/
carboplatin or irinotecan/carboplatin. The response was measured by CT/PET
at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumour
samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood
samples for circulating tumour cells (CTCs) were also obtained at the baseline
and before each treatment cycle till progression of disease. Results: Forty (40)
patients, median age 66 (range 39-83) were enrolled treated on this study.
Seven (7) patients either died or progressed before the first evaluation scan.
Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%)
complete and 13 (38%) partial responses. Four patients (12%) achieved stable
disease while 7 patients (20%) progressed during the treatment. There was
no PFS difference in the two first line treatment arms (median 28 weeks in
experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-
2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity
profile was similar to standard irinotecan, with the incidence of grade III/
IV diarrhea seen in the experimental arm of 11% compared with 25% in the
standard arm. Biomarker data was available in case of 24 patients, which
suggested that there was no difference in response rates or survival according
to baseline CD44s or CD44v6 expression. A possible correlation between the
number of CTCs and tumour response and relapse was noticed. Conclusion:
HA-irinotecan is well tolerated and has shown activity in the treatment of
extensive stage small cell lung cancer. However, no improvement in efficacy
was seen in CD44s+ or CD44v6+ SCLC treated with HA-irinotecan. Further
strategies to combine HA with other chemotherapeutic agents may be
warranted.
Keywords: Hyaluronic acid, small cell lung cancer, CD44, irinotecan
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
MONDAY, DECEMBER 5, 2016
P1.07-005 A RETROSPECTIVE STUDY OF SEQUENTIAL
CHEMORADIOTHERAPY FOR LD-SCLC PATIENTS IN WHOM
CONCURRENT THERAPY IS NOT INDICATED
Sayaka Ohara 1 , Shintaro Kanda 2 , Keiko Goto 3 , Hideaki Shiraishi 2 , Hitomi
Okuma 3 , Kota Itahashi 2 , Yasushi Goto 2 , Hidehito Horinouchi 2 , Yutaka
Fujiwara 4 , Hiroshi Nokihara 2 , Yoshinori Ito 3 , Noboru Yamamoto 2 , Kazuhiro
Usui 1 , Yuichiro Ohe 3
1 Division of Respirology, NTT Medical Center Tokyo, Tokyo/Japan, 2 Department of
Thoracic Oncology, National Cancer Center Hospital, Tokyo/Japan, 3 National Cancer
Center Hospital, Tokyo/Japan, 4 Thoracic Oncology, National Cancer Center Hospital,
Tokyo/Japan
Background: The standard treatment for limited-disease small-cell lung
cancer (LD-SCLC) is a combination of cisplatin-doublet chemotherapy and
concurrent thoracic radiotherapy. However, sequential radiotherapy, rather
than concurrent radiotherapy, is selected for some cases because of concerns
regarding the irradiation field, patient age, comorbidities, or performance
status. Nevertheless, the efficacy of sequential chemoradiotherapy in
patients in whom concurrent chemoradiotherapy is contraindicated is not
well known. Methods: We retrospectively analyzed 286 patients with LD-SCLC
at the National Cancer Center Hospital and the NTT Medical Center in Japan
between 2000 and 2014. We then compared the clinical characteristics and
treatment outcomes of patients undergoing sequential radiotherapy with
those undergoing concurrent radiotherapy. Results: One hundred and eightythree
patients received concurrent chemoradiotherapy and 30 received
sequential chemoradiotherapy. The median age of the patients was 64 years
(range, 18-81 years) for the concurrent group and 71.5 years (50-83 years) for
the sequential group. The concurrent group contained 43 women (23%), while
the sequential group contained 9 women (30%). The major reasons for the
selection of sequential radiotherapy were patient age (13 patients), a large
irradiation field (8 patients), and comorbidities (5 patients). In the sequential
group, 23 (77%) received conventional radiotherapy, whereas 7 (23%) received
accelerated hyperfractionated radiotherapy. The median overall survival
period was 34.5 months for the concurrent group and 27.6 months for the
sequential group (P = 0.39). The 2-, 3-, and 5-year survival rates were 71%, 50%,
and 40% for the concurrent group and 56%, 56%, and 35% for the sequential
group. Recurrence was seen in 149 patients (81%) in the concurrent group and
19 patients (63%) in the sequential group. Conclusion: We obtained treatment
outcomes for patients who could not receive concurrent radiotherapy but
could complete sequential radiotherapy that were comparable with the
outcomes for those who received concurrent radiotherapy. For patients
in whom concurrent chemoradiotherapy is not indicated, sequential
chemoradiotherapy should be considered.
Keywords: sequential chemoradiotherapy, LD-SCLC
S360 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017