Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
observed was 17.4 % in the second line and 20 % in third line or more, with a
progression-free survival (PFS) of 4 months (95% CI: 2.3-5.4) and 10 months
(95% CI 2.9-18), respectively. The average number of administered cycles was
6: 1 in PS2 and 18 when there was pseudoprogression (n=5). The observed
irAEs was: grade GI 11 (34 %), GII 4 (12 %) and GIII 1 (3 %), 6% pneumonitis (with
previous radiotherapy), 3% autoimmune hepatopathy, 3% pemphigoid and
3% hypothryroidism. Global survival (GS) in PS0 was 6.5 months (95% CI:
4.6-8.3), PS1 of 7.4 (95% CI: 6-8.7) and PS2 of 1 (95% CI: 0, 67-0), with p0.001.
The GS with brain metastasis was 3 months (95% CI: 1.7-4.2) vs. 7.9 months (CI
95%6-8.7), with p 0.001, in patients without brain metastasis. Conclusion: In
our series, nivolumab was well tolerated and demonstrated clinical benefit
both in second and in third line, except in patients with PS2 and/or brain
metastases. Patients that present pseudoprogression obtain major benefit
and more occurrence incidence of irAEs (possible indicator of response).
External validity is limited by the small number of patients and this is not a
randomized study
Keywords: compassionate, Nivolumab, non-small lung cancer, chemotherapy
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-046 SAFETY, CLINICAL ACTIVITY AND BIOMARKER RESULTS
FROM A PHASE IB STUDY OF ERLOTINIB PLUS ATEZOLIZUMAB IN
ADVANCED NSCLC
Charles Rudin 1 , ANDRÉS CERVANTES 2 , AFSHIN DOWLATI 3 , BENJAMIN
BESSE 4 , BRIGETTE MA 5 , DANIEL COSTA 6 , PETER SCHMID 7 , REBECCA
HEIST 8 , VICTORIA VILLAFLOR 9 , INDRANI SARKAR 10 , MAHRUKH
HUSENI 10 , PAUL FOSTER 10 , CAROL O’HEAR 10 , SCOTT GETTINGER 11
1 Memorial Sloan Kettering Cancer Center, New York/United States of America,
2 University of Valencia, University of Valencia/Spain, 3 University Hospitals Case
Medical Center, Cleveland/OH/United States of America, 4 Department of Cancer
Medicine, Gustave Roussy, Orsay/France, 5 Phase I Clinical Trial Center, Chinese
University of Hong Kong, Hong Kong/China, 6 Beth Israel Deaconess Medical Center,
Boston/MA/United States of America, 7 Barts Cancer Institute, London/United
Kingdom, 8 Massachusetts General Hospital, Boston/MA/United States of America,
9 Northwestern University, Chicago/IL/United States of America, 10 Genentech, Inc.,
South San Francisco/CA/United States of America, 11 Yale Cancer Center, New Haven/
CT/United States of America
Background: Targeted therapy with erlotinib is effective in reducing tumor
burden in EGFR-mutant non-small cell lung cancer (NSCLC). However,
resistance to therapy develops almost universally. Atezolizumab, an
engineered mAb that inhibits binding of PD-L1 to its receptors, PD-1 and
B7.1, has demonstrated promising monotherapy activity in NSCLC. Given
that atezolizumab may enhance and perpetuate anti-tumor immunity, we
hypothesized that combining atezolizumab with erlotinib may improve
both clinical response and durability in EGFR-mutant NSCLC. Methods:
This Phase Ib study consisted of a safety-evaluation stage in patients with
NSCLC regardless of EGFR status followed by an expansion stage in TKInaïve
patients with tumors harboring activating EGFR mutations. Patients
were enrolled regardless of PD-L1 status. After a 7-day run-in with 150mg
erlotinib PO QD alone, patients received 150mg erlotinib PO QD and 1200mg
atezolizumab IV q3w. To evaluate immune biology, biopsies were obtained
in expansion-stage patients pre-treatment, after erlotinib run-in, at weeks
4-6, and at progression. The primary objective was to evaluate the safety and
tolerability of the combination. Secondary objectives included evaluation of
the clinical activity per RECIST v1.1. Data cutoff, 11 April 2016. Results: Twentyeight
patients (safety stage, n = 8; expansion stage, n = 20) who received ≥ 1
dose of erlotinib or atezolizumab were considered safety evaluable. Median
age was 61y (range, 47-84); median survival follow-up was 11.2mo (range,
0.8-24.2). The incidence of either treatment-related G3-4 AEs was 39% and
for serious AEs, 50%. The most common atezolizumab-related G3-4 AEs were
pyrexia and increased ALT. No pneumonitis was reported. No treatmentrelated
G5 AEs occurred. Five patients discontinued atezolizumab due to
treatment-emergent AEs. No DLTs were observed. In the expansion-stage
population, ORR was 75% (95% CI, 51-91). Disease control rate (CR + PR + SD ≥
24 weeks) was 90% (95% CI, 68-99), median PFS was 11.3mo (95% CI, 8.4-NE)
and median DOR was 9.7mo (range, 4.2-11.7). Increases in intratumoral CD8+
T cells post-erlotinib run-in were observed in 8/13 evaluable paired biopsies.
Higher intratumoral CD8+ T-cell prevalence and immune gene expression
signatures at baseline were associated with improved PFS. Conclusion:
The combination of full dose erlotinib plus atezolizumab demonstrated
a manageable safety profile. While response rates and median PFS for
combination treatment appear similar to those observed with erlotinib
monotherapy, the addition of atezolizumab to erlotinib may lead to more
durable clinical responses in some patients. Additional follow-up is required
to evaluate the full potential of this combination treatment. NCT02013219
Keywords: atezolizumab, NSCLC, Immunotherapy, Erlotinib
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-047 LOCAL EXPERIENCE IN AN EXPANDED ACCESS
PROGRAM OF NIVOLUMAB IN ADVANCED NON-SMALL CELL LUNG
CANCER IN BRAZIL
Luiz H. Araujo, Clarissa Baldotto, Cícero Martins, Mauro Zukin
Instituto Coi de Educação E Pesquisa (Icoi) and Núcleo de Oncologia Torácica (Not),
Rio de Janeiro/Brazil
Background: Nivolumab is a new standard-of-care in platinum-refractory
Non-small cell lung cancer (NSCLC), with significant survival increment in
comparison to docetaxel shown in two phase 3 trials. Herein, we report
the local experience in an expanded access program in Brazil. Methods:
Patients with recurrent or metastatic NSCLC, treated with at least one prior
chemotherapy regimen, were potentially eligible. Overall, three hundred
twenty-one patients were screened in the country, and 287 were enrolled.
Around 10% of these (N=29) were treated in a single cancer institution in Rio
de Janeiro. The aim was to describe the early outcome in these 29 patients.
Results: Median age was 64 years (range 37-83), most patients were male
(62%), white (66%), smoker or former smoker (21% and 55%, respectively).
Most cases (59%) were classified as non-squamous, and only 3 had a
documented EGFR mutation. Sixty-two percent had received 2 or more prior
chemotherapy lines. After a median follow-up of 4.9 months (95% CI, 4.2-5.5),
1 partial response (3%) was documented, and 13 patients (45%) presented
with disease stabilization by RECIST 1.1. Median PFS and OS were not reached,
and 6-month OS was 52%. Seventeen patients (59%) had at least 1 adverse
event, the most common being asthenia (9 patients). Only 1 (3%) grade 3
event was documented. Conclusion: Nivolumab was well tolerated and led to
disease control in 48% of patients in this early analysis, after a short followup.
Survival data will be updated for presentation.
Keywords: immunotherapy, nivolumab, lung cancer, survival.
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-048 A PHASE I/II TRIAL EVALUATING THE COMBINATION OF
STEREOTACTIC BODY RADIOTHERAPY AND PEMBROLIZUMAB IN
METASTATIC NSCLC
Roy Decker 1 , Sarah Goldberg 2 , Sameer Nath 3 , Zain Husain 1 , Rogerio
Lilenbaum 4 , Kurt Schalper 5 , Anne Chiang 6 , Mehmet Altan 7 , Daniel Zelterman 8 ,
Susan Kaech 4 , Roy Herbst 9 , Scott Gettinger 3
1 Therapeutic Radiology, Yale School of Medicine, New Haven/CT/United States
of America, 2 Medical Oncology, Yale University, New Haven/CT/United States of
America, 3 Therapeutic Radiology, Yale School of Medicine, New Haven/United
States of America, 4 Yale School of Medicine, New Haven/CT/United States of
America, 5 Yale Cancer Center, New Haven/United States of America, 6 Yale University
School of Medicine, New Haven/CT/United States of America, 7 Thoracic Oncology,
Yale Cancer Center, New Haven/United States of America, 8 Yale School of Medicine,
New Haven/United States of America, 9 Medical Oncology, Yale Cancer Center, New
Haven, Ct/CT/United States of America
Background: Immune checkpoint inhibitors are taking on a growing role in the
treatment of patients with metastatic NSCLC. Pre-clinical evidence suggests
that radiotherapy may increase the frequency, or enhance the strength of
the host anti-cancer immune response. We report the preliminary results of
an ongoing phase I/II trial combining stereotactic body radiotherapy (SBRT)
and the anti-PD-1 antibody pembrolizumab in patients with metastatic
NSCLC. Methods: Eligible patients are those with metastatic NSCLC who
have received no prior immune-directed therapy, and have at least 2 sites
of measurable disease as per RECIST 1.1. PD-L1 expression is not required for
study entry. All patients are treated with pembrolizumab at 200 mg every 3
weeks until development of progressive disease by immune-related RECIST
criteria (irPD). After irPD, patients receive SBRT to a single site of disease and
continue pembrolizumab. The primary endpoint is safety and tolerability.
Secondary endpoints include the pre- and post-SBRT overall response rate.
Results: 27 patients with advanced NSCLC have enrolled and started trial
therapy. The overall response rate (irPR and irCR) to the initial course of
pembrolizumab is 35%. To date, 13 patients have had irPD: 5 were not eligible
for SBRT and stopped study treatment (2 developed new brain metastases,
3 had decline in PS), and 8 patients received SBRT to a single site of disease
(6 thoracic, 1 adrenal, 1 vertebral) and continued pembrolizumab. 5 of these
patients are evaluable for post-SBRT response: 1 patient had confirmed irPD,
4 have irSD and continue pembrolizumab post-SBRT at a median duration
of 3 months (range 1 to 5 months). 2 of the 4 patients with irSD have had >
20% decrease in the sum of diameters of their unirradiated targets, since
SBRT. Regarding adverse events, in the pre-SBRT phase 6 of 27 patients
S684 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017