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
P1.07-006 PRECLINICAL SUPPORT FOR EVALUATION OF
IRINOTECAN LIPOSOME INJECTION (NAL-IRI, MM-398) IN SMALL
CELL LUNG CANCER
Shannon Leonard, Helen Lee, Stephan Klinz, Nancy Paz, Jonathan Fitzgerald,
Bart Hendriks
Merrimack Pharmaceuticals, Inc., Cambridge/MA/United States of America
Background: Nal-IRI (irinotecan liposome injection, MM-398, ONIVYDE ® ),
in combination with 5-fluorouracil and leucovorin, is currently approved by
the FDA for treatment of patients with advanced pancreatic cancer who
have progressed on gemcitabine-based therapies. Nal-IRI is designed for
extended circulation relative to non-liposomal irinotecan and to exploit leaky
tumor vasculature for enhanced drug delivery to tumors. Following tumor
deposition, nal-IRI is taken up by phagocytic cells followed by irinotecan
release and conversion to its active metabolite SN-38 in the tumors.
Sustained inhibition of topoisomerase 1 (TOP1) by extended SN-38 delivery is
hypothesized to enable superior anti-tumor activity compared to traditional
TOP1 inhibitors. Topotecan, a TOP1 inhibitor, is currently a standard of care
for second-line treatment of small cell lung cancer (SCLC). Here, we evaluate
nal-IRI compared to topotecan in preclinical models of SCLC. Methods: Antitumor
activity of nal-IRI as a monotherapy was evaluated in DMS-53 and
NCI-H1048 xenograft models. Cells were implanted subcutaneously into right
flanks of NOD-SCID mice; treatments were initiated when tumors had reached
approximately 280 mm 3 . Nal-IRI was dosed at 16 mg/kg salt, q1w, which is
equivalent to a proposed clinical dose of 90 mg/m 2 free base, q2w. Topotecan
was dosed at 0.83 mg/kg/week, Day 1-2 every 7 days, which approximates a
clinical dose intensity of 1.5 mg/m 2 (Day 1-5 every 21 days). Tumor metabolite
levels were compared in mice treated with nal-IRI or non-liposomal irinotecan
at 24 hours post-injection, using previously established high performance
liquid chromatography methods. Results: Carboxylesterase activity and
sensitivity to SN-38 in mouse SCLC models were comparable to those
measured in tumor types where either nal-IRI or irinotecan HCl has proven
to be efficacious clinically (e.g. pancreatic cancer, colorectal cancer). Nal-IRI
delivered irinotecan to SCLC tumors to a similar or greater extent than other
tumor types including pancreatic tumors. The tumor irinotecan and SN-38
levels of nal-IRI (16 mg/kg salt) were 12 to 57-fold and 5 to 20-fold higher than
non-liposomal irinotecan (30 mg/kg salt), respectively. Nal-IRI demonstrated
anti-tumor activity in both xenograft models of SCLC at clinically relevant
dose levels, and resulted in complete or partial responses after 4 cycles in
NCI-H1048 or DMS-53 models, respectively, compared with topotecan which
had limited tumor growth control. Conclusion: This study demonstrated
that nal-IRI is more active than topotecan at clinically relevant doses in
SCLC preclinical models, and thus support further clinical development of
nal-IRI versus topotecan in patients with SCLC that have progressed on prior
platinum-based therapy.
Keywords: small cell lung cancer treatment, irinotecan liposome, MM-398,
topoisomerase 1 inhibitor
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
MONDAY, DECEMBER 5, 2016
P1.07-007 CLINICAL OUTCOMES OF PATIENTS WITH LS-
SCLC TREATED WITH CHEMORADIOTHERAPY. CAN WE FIND
CANDIDATES FOR SALVAGE SURGERY?
Junichi Shimizu 1 , Yuko Oya 1 , Kosuke Tanaka 1 , Chiaki Kondo 1 , Hiromi Furuta 1 ,
Tatsuya Yoshida 1 , Yoshitsugu Horio 1 , Yukinori Sakao 2 , Yasushi Yatabe 3 , Toyoaki
Hida 1
1 Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya/Japan, 2 Thoracic
Surgery, Aichi Cancer Center Hospital, Nagoya/Japan, 3 Pathology and Molecular
Diagnostics, Aichi Cancer Center Hospital, Nagoya/Japan
Background: Although small cell lung cancer (SCLC) is generally considered a
systemic disease even in patients with limited stage (LS). Selected recurrent
LS-SCLC patients after chemoradiation treatment have been reported long
survival with receiving salvage surgery. Purpose of this study was to find
candidates for salvage surgery. Methods: We retrospectively reviewed the
charts of 43 consecutive patients who were treated with chemoradiotherapy
for LS-SCLC at our hospital from January 2011 to December 2015 to search for
the patients with locoregional progression without mediastinal lymph node
involvement. Results: Of the 43 patients, the median age was 69 (38-83), 91%
were male and all of them had ECOG PS 0 or 1. Clinical stage: IIA (12%), IIIA
(53%), IIIB (35%). 35 (81%) received hyperfractionated RT (45Gy/30fr/3w).
Objective response rate was 95%. One patient died of pneumonia. The median
survival time was 1584 days and the median progression free survival was 280
days. 33 (77%) demonstrated disease progression. The first progression site
was distant (include pulmonary metastasis and malignant pleural effusion)
in 17, locoregional in 11, lymph node metastasis out of the radiation field in
2 and both distant and locoregional in 3. In the locoregional progression
patients, 6 developed mediastinal lymph node progression in their clinical
courses. Finally, 5 in 33 progressive patients had locoregional progression
without mediastinal lymph node progression, and were thought possible
candidates for salvage surgery. Conclusion: Most of the patients experienced
distant metastasis and/or mediastinal lymph node progression. About 15%
of patients who presented with apparently localized disease at the primary
pulmonary site after chemoradiation might become possible candidates for
salvage surgery.
Keywords: salvage surgery, limited stage, SCLC
POSTER SESSION 1 - P1.07: SCLC/NEUROENDOCRINE TUMORS
DRUG TREATMENT ALONE AND IN COMBINATION WITH RADIOTHERAPY –
MONDAY, DECEMBER 5, 2016
P1.07-008 LOMUSTINE ENDOXAN VP16 AS SECOND OR FURTHER
LINE FOR RECURRENT OR PROGRESSIVE BRAIN METASTASES
FROM SCLC
Charles Naltet 1 , Audrey Dugué 1 , Catherine Dubos 1 , Pascal Dô 1 , Serge Danhier 1 ,
Delphine Lerouge 1 , Christos Chouaid 2 , Radj Gervais 1
1 Baclesse, Caen/France, 2 Chic, Créteil/France
Background: Up to fifty percent of patients with small-cell lung cancer
(SCLC) will experience brain metastases (BM) during the whole course of
their disease. The oral regimen Lomustine Cyclophosphamide Etoposide
(LCE) has been tested in SCLC as second line treatment and was shown to
be equivalent to the intravenous regimen Cyclophosphamide Adriamycin
Vincristine (Gervais R et al. Clin Lung Cancer 2015;16:100-5). This retrospective
study evaluates the cerebral response rate (CRR) of this oral chemotherapy
on brain metastases (BM) from SCLC relapsing after platinum-based
chemotherapy. Methods: Patients with disease progression after one or
more prior chemotherapy regimens for SCLC were included if they had at
least one measurable BM according to RECIST 1.1, with PS