Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
(22%) developed grade 3 treatment-related toxicity (2 colitis, hepatitis,
pneumonitis, hypothyroidism, conjunctivitis). In the SBRT and post-SBRT
phases, there have been no grade 2 or greater treatment-related events.
Conclusion: The addition of SBRT to pembrolizumab has not resulted in an
increase in treatment-related toxicity. Several patients who had serially
confirmed irPD to pembrolizumab monotherapy underwent SBRT and now
have irSD, with some evidence of tumor regression. Updated results will be
presented.
Keywords: immune checkpoint inhibitor, abscopal, SBRT, radiation
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-049 DENDRITIC CELLS MODIFIED WITH TUMOR-
ASSOCIATED ANTIGEN GENE DEMONSTRATE ENHANCED
ANTITUMOR EFFECT AGAINST LUNG CANCER
Tao Jiang, Caicun Zhou
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University
School of Medicine, Shanghai/China
Background: Immunotherapy involving dendritic cells (DCs) vaccine has the
potential to overcome the bottleneck of cancer therapy. Methods: Here, we
engineered Lewis Lung cancer cells (LLC) and bone marrow derived DCs to
express tumor-associated antigen (TAA), ovalbumin (OVA) via lentiviral vector
plasmid encoding OVA gene. We then tested the anti-tumor effect of modified
DCs both in vitro and in vivo. Results: The results demonstrated that in vitro
modified DCs could dramatically enhance T cells proliferation (P < 0.01) and kill
LLC significantly than control groups (P < 0.05). Moreover, modified DCs can
reduce tumor size and prolong the survival of tumor-bearing mice than control
groups (P < 0.01, P < 0.01; respectively). Modified DCs enhanced homing to
T-cell-rich compartments and triggered naïve T cells to become cytotoxic T
lymphocytes, which exhibited significant infiltration into the tumors.
Interestingly, modified DCs also markedly reduced tumor cells harboring stem
cell markers in mice (P < 0.05), suggesting the potential role of eliminating
cancer stem-like cells in vivo.
surgically, but 30%-70% of patients experience post-resection recurrence and
succumb to disease. Adjuvant chemotherapy is the standard of care for fully
resected NSCLC (stages IB [tumors ≥4 cm]-IIIA), and although cisplatin-based
chemotherapy provides some benefit, the 5-year absolute survival benefit is
≈5%, underscoring the unmet need. Atezolizumab is an anti-PD-L1 monoclonal
antibody that inhibits PD-L1 from binding to its receptors PD-1 and B7.1,
thereby restoring anti-tumor immune response. Atezolizumab monotherapy
has demonstrated promising efficacy and tolerable safety in patients with
previously-treated advanced NSCLC, with a survival benefit observed across
all PD-L1 expression levels. Given the need to improve survival for patients
with early-stage NSCLC, IMpower010 (NCT02486718), a global Phase III
randomized, open-label trial, has been initiated to compare the efficacy and
safety of atezolizumab with best supportive care (BSC), following adjuvant
cisplatin-based chemotherapy in patients with resected stage IB (tumors ≥4
cm)-IIIA NSCLC. Methods: Eligibility criteria include complete tumor resection
4-12 weeks prior to enrollment for pathologic stage IB (tumors ≥4 cm)–IIIA
NSCLC. Patients must have adequately recovered from surgery, be eligible
to receive cisplatin-based adjuvant chemotherapy and have an ECOG PS 0-1.
Exclusion criteria include the presence of other malignancies, use of hormonal
cancer or radiation therapy within 5 years, prior chemotherapy, autoimmune
disease or exposure to prior immunotherapy. Approximately 1127 patients,
regardless of PD-L1 expression status, will be enrolled. Eligible patients will
receive up to four 21-day cycles of cisplatin-based chemotherapy (cisplatin
[75 mg/m 2 IV, day 1] + either vinorelbine [30 mg/m 2 IV days 1, 8], docetaxel
[75 mg/m 2 IV day 1] or gemcitabine [1250 mg/m 2 IV days 1, 8], or pemetrexed
[500 mg/m 2 IV day 1; non-squamous NSCLC only]). Adjuvant radiation
therapy is not permitted. Following adjuvant treatment, eligible patients
will be randomized 1:1 to receive atezolizumab (1200 mg q3w, 16 cycles) or
BSC. Stratification factors will include sex, histology (squamous vs nonsquamous),
extent of disease (stage IB vs II vs IIIA) and PD-L1 expression by
IHC (TC, tumor cell; IC, tumor-infiltrating immune cell; TC2/3 [≥5% expressing
PD-L1] and any IC vs TC0/1 [