Virtual Library
Start Your Search
Manish Patel
Author of
-
+
P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.04-33 - Retrospective Descriptive Analysis of Metformin with Atezolizumab in Advanced Non-Small Cell Lung Cancer in The OAK Trial (ID 12388)
16:45 - 18:00 | Author(s): Manish Patel
- Abstract
Background
The randomized Phase III OAK trial investigated atezolizumab (anti–PD-L1) for treatment of advanced or metastatic previously-treated NSCLC. Atezolizumab significantly improved OS compared with docetaxel. Given that emerging studies have identified an association between metformin use and antitumor activity/immune interactions, we retrospectively explored metformin use in patients in the OAK study.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients received atezolizumab (1200 mg IV every 3 weeks [q3w]) until PD or loss of clinical benefit or docetaxel (75 mg/m2 IV q3w) until PD/unacceptable toxicity. Patients who received atezolizumab or docetaxel and did or did not receive metformin as concomitant therapy were retrospectively evaluated for ORR, PFS and OS (data cutoff, July 7, 2016). Unadjusted and adjusted comparisons between metformin users and non-metformin users were done.
4c3880bb027f159e801041b1021e88e8 Result
Of the 425 patients randomized to atezolizumab, 36 received metformin; of the 425 patients randomized to docetaxel, 35 received metformin. Key baseline characteristics are shown in the table. Most metformin users started metformin before or within 30 days of study start (92% and 7% respectively). There was a numerical improvement in ORR in Atezo-Met patients compared with Atezo-NoMet patients (25% vs 13%; unadjusted P = 0.038 [adjusted = 0.093]), whereas there was no statistically significant improvement in ORR in Doc-Met patients compared with Doc-NoMet patients (17% vs 13%; unadjusted P = 0.499 [adjusted = 0.295]). There were no observable differences in PFS or OS in either the Atezo-Met vs Atezo-NoMet or Doc-Met vs Doc-NoMet groups (median PFS, 2.8 vs 2.8 mo and 4.2 vs 4.0 mo, respectively; median OS, 12.6 vs 14.1 mo and 9.1 vs 9.7 mo, respectively).
8eea62084ca7e541d918e823422bd82e Conclusion
Encouraging response rates suggest patients may benefit from receiving concomitant metformin treatment with atezolizumab. Lack of difference in PFS and OS may be due to lack of treatment effect or lack of statistical power and requires further prospective investigation.
6f8b794f3246b0c1e1780bb4d4d5dc53Table. Characteristics of Patients Who Received Atezolizumab (Atezo) or Docetaxel (Doc) Combined With Metformin (Met) or No-Metformin (NoMet)
Atezo-Met, n (%) (n = 36)
Atezo-NoMet, n (%) (n = 389)
Doc-Met, n (%)
(n = 35)Doc-NoMet, n (%)
(n = 390)Diabetes mellitus type 2
33 (91.6)
28 (7.2)
33 (94.3)
26 (6.7)
Sex
Male
28 (77.8)
233 (59.9)
28 (80.0)
231 (59.2)
Female
8 (22.2)
156 (40.1)
7 (20.0)
159 (40.8)
Tobacco use history
Never smoker
2 (5.6)
82 (21.1)
2 (5.7)
70 (17.9)
Current/previous smoker
34 (94.4)
307 (78.9)
33 (94.3)
320 (82.1)
Histology
Nonsquamous
22 (61.1)
291 (74.8)
21 (60.0)
294 (75.4)
Squamous
14 (38.9)
98 (25.2)
14 (40.0)
96 (24.6)
No. of prior therapies
1
30 (83.3)
290 (74.6)
24 (68.6)
296 (75.9)
ECOG performance status at baseline
0
15 (41.7)
140 (36.0)
12 (34.3)
148 (37.9)
1
21 (58.3)
249 (64.0)
23 (65.7)
242 (62.1)
EGFR mutation status
Positive
1 (2.8)
41 (10.5)
1 (2.9)
42 (10.8)
PD-L1 IHC subgroup
TC3 or IC3
(PD-L1 ≥ 50% TC or 10% IC)11 (30.6)
61 (15.7)
5 (14.3)
60 (15.4)
TC1/2/3 or IC1/2/3
(PD-L1 ≥ 1% on TC or IC)27 (75.0)
214 (55.0)
19 (54.3)
203 (52.1)
TC0 and IC0
(PD-L1 < 1% on TC and IC)9 (25.0)
171 (44.0)
16 (45.7)
183 (46.9)
TC, tumor cell; IC, tumor-infiltrating immune cell.
-
+
P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.01-83 - Use of Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus in Preclinical Models of NSCLC (ID 12152)
12:00 - 13:30 | Presenting Author(s): Manish Patel
- Abstract
Background
Oncolytic virus therapy has demonstrated efficacy in numerous tumor models including non-small cell lung cancer. One of the limitations of viral therapy for metastatic lung cancer is that systemic administration can be hindered by complement and antiviral immunity. Thus, we investigated the possibility of using ex-vivo infected blood outgrowth endothelial cells with tumor-homing properties to deliver oncolytic VSV-IFNβ in preclinical models of NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
BOECs were obtained from either human donors or C57/Bl6 mice. Cells were confirmed to maintain the BOEC phenotype and growth characteristics. Indiana strains of VSV were engineered to produce GFP or IFNβ and were titered on Vero cells using either plaque assay or limiting dilution assay. Human NSCLC cell lines, H2009 and H2030 were used for in vitro assays. A549 expressing firefly luciferase cells were used to induce lung metastasis in NOD/SCID mice and treated with BOECs, VSV-IFNβ, or BOECs-infected with VSV-IFNβ. Additionally, syngeneic murine adenocarcinoma cell line, LM2 was used in vivo in A/J mice (n=5).
4c3880bb027f159e801041b1021e88e8 Result
BOEC cells were able to home to metastatic LM2 lung tumors and were retained there for up to 72 hours post-infusion. BOEC cells were retained within lung tumors of mice bearing tumors, but there were none detected in lungs of mice without lung tumors. Both human and murine BOECs could be infected and lysed by VSV-GFP and VSV-IFNβ, however, VSV-IFNβ was attenuated compared to VSV-GFP. Maximal viral titer was obtained at 24 or 48 hours for VSV-GFP and VSV-IFNβ, respectively. Co-culture experiments showed near complete lysis of H2009 cells using infected BOECs. Both H2009 and H2030 cells were lysed efficiently by infected BOECs while naked VSV was completely inhibited in the presence anti-VSV neutralizing antibodies. Using Firefly luciferase-expressing A549 cells, metastatic lung tumors were induced in NOD/SCID mice. Compared to BOEC alone and PBS-treated mice, VSV-IFNβ-infected BOECs resulted in superior antitumor efficacy as measured by luciferase activity (p<0.02). Infected BOECs resulted in superior survival of mice compared to VSV-IFNβ alone (n=10, p<0.05). Using immune competent A/J mice, infected BOECs trended toward improved antitumor efficacy to BOEC alone and intravenous VSV-IFNβ treatment (n=5, p=0.09). Replicating virus was recovered only from lungs of infected BOEC treated mice.
8eea62084ca7e541d918e823422bd82e Conclusion
BOECs can be used as cellular carrier for systemic delivery of oncolytic VSV-IFNβ. For clinical translation, the use of cellular carriers might be an effective method of virotherapy for metastatic NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
