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Penelope Bradbury
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MA 10 - Immunotherapy I (ID 664)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:S. Wang, Robert Pirker
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 303 + 304
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MA 10.01 - Durvalumab ± Tremelimumab with Platinum-Doublets in Non-Small Cell Lung Cancer: Canadian Cancer Trials Group Study IND.226 (ID 8700)
11:00 - 11:05 | Author(s): Penelope Bradbury
- Abstract
- Presentation
Background:
Anti-PD1-monotherapy has activity in NSCLC with improved outcomes compared to chemotherapy. Preclinical, and early clinical data, suggests that combining immune checkpoint inhibitors and platinum-based chemotherapy may be synergistic. We examined the cohort of patients (pts) with metastatic NSCLC, with no prior therapy for advanced disease, from this multicentre phase Ib trial. The primary objective was to establish the recommend phase II doses of durvalumab (Du) ± tremelimumab (Tr) in combination with platinum-doublet chemotherapy. Secondary objectives included assessing safety, tolerability, and antitumour activity of the 4-drug combination.
Method:
Pts were treated with Du±Tr at one of 4 dose levels (DL) concomitantly with either pemetrexed (Pem) +cisplatin/carboplatin followed by maintenance Pem for nonsquamous histology or gemcitabine (Gem) +cisplatin/carboplatin for squamous tumours. At DL0 Du 15 mg/kg IV q3wks was added; DL1 added Du 15mg/kg q3wk + Tr 1mg/kg x1 dose; DL2a added Du 15mg/kg q3wk + Tr 1 mg/kg q6wk x multiple doses; DL2b added Du 15mg/kg q3wk + Tr 3 mg/kg q6wk (1 dose with cycle 1 and 2 doses with maintenance pem), DL3 and DL4 added a fixed doses of Du 1125mg/Tr 56 mg and Du 1500 mg/ Tr 75 mg q3wk respectively. Du could continue until 1 year or unacceptable toxicity.
Result:
To date, 45 pts (median age=62 (range 36-78); 44% male, 100% ECOG PS≤1) have received 346 cycles in the Pem-platinum cohort while 9 pts (median age=64 (range 57-80); 78% male, 100% ECOG PS≤1) have been received 55 cycles in the Gem-platinum group. Most adverse events were ≤grade 2 and attributed to chemotherapy. Immunotherapy-related adverse events (irAEs) ≥ grade 3 were observed in 27% of patients and were more commonly reported with the addition of Tr. In the Pem-platinum cohort, diarrhea (n=5), fatigue (n=4) and elevated lipase (n=4) were the most come irAEs ≥ grade 3, while rash, pneumonitis and hypothyroidism occurred in 1 pt each after the introduction of Tr. In the Gem-platinum cohort, irAEs ≥ grade 3 were fatigue and rash (1 pt each at DL2b) and elevated lipase (1 pt at DL3). The objective response rate in 35 evaluable patients receiving Pem-platinum was 57.1% (95% CI=39.4, 73.7 ) and 37.5% (95% CI=8.5, 75.5) in the 8 evaluable patients receiving Gem-Platinum.
Conclusion:
The combination of Du±Tr can be safely administered with platinum-doublet chemotherapy with encouraging preliminary response data. Adding Tr may increase ≥ grade 3 irAE hence patient selection and early intervention is key to managing irAEs. *contributed equally
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OA 17 - Immunotherapy II (ID 683)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yuichiro Ohe, Anne Tsao
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 301 + 302
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OA 17.09 - Discussant - OA 17.05, OA 17.06, OA 17.07, OA 17.08 (ID 10803)
15:55 - 16:10 | Presenting Author(s): Penelope Bradbury
- Abstract
- Presentation
Abstract not provided
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-032 - A Randomized Phase Ii Trial of Selumetinib + Platinum-pemetrexed (Pem-c) in Kras Wildtype (Wt)/Unknown NSCLC: CCTG Ind219 (ID 9083)
09:00 - 09:00 | Author(s): Penelope Bradbury
- Abstract
Background:
Selumetinib (SEL), an oral inhibitor of MEK 1 and 2, could be particularly effective in tumours with an activated Ras/Raf/MEK/ERK pathway, but has not been fully studied in KRAS WT nor in the first-line setting. The scheduling of SEL with chemotherapy might impact efficacy and/or toxicity.
Method:
IND219 is an open-label three-arm study of PEM-C±SEL. Arm A: PEM-C+SEL days 2-19; Arm B: PEM-C+SEL days 1-21; Arm C: PEM-C alone. Primary objective was response rate (ORR); secondary objectives were tolerability and progression-free survival (PFS). Pts were stratified by KRAS WT versus unknown and cisplatin versus carboplatin. Before the planned interim analysis (60 pts), pts were allocated 1:1:1 to arm A, B or C, with a plan to continue either Arm A or B plus Arm C a 3:1 ratio to ensure that the final analysis includes Arm A or B and Arm C in a 2:1 ratio. The trial would stop if neither Arm A or B had > 4 responses; if both did, the arm would be selected based on response and toxicity data. Correlative studies included genomic testing.
Result:
Arm A/B/C enrolled 20/21/21 pts. PEM-C exposure was lower with SEL (median cycles 5 versus 6 for Arm C). Seven pts on Arm A (35%; 95% CI 15-59% median duration 3.8m), 13 on Arm B (62%; 95% CI 38-82%; median duration 6.3m), and 5 on Arm C (24%; 95% CI 8-47%; median duration 11.6m) had PR, meeting the criteria to continue. PFS was 7.5m (95% CI 4.0 to 9.0 m) for Arm A, 6.7m (95% CI 4.1 to 8.2 m) on Arm B, and 4.0m on Arm C (95% CI 1.4 to 6.8 m). HR for PFS of Arm A over Arm C was 0.76 (95% CI 0.38 to 1.51, 2-sided p=0.42); HR for PFS of Arm B over Arm C was 0.75 (95% CI 0.37 to 1.54, p=0.43). After adjusting for age, performance status, gender and KRAS, PFS comparisons remained NS. Toxicity was most commonly grade 1-2, but more frequent with SEL especially mucositis, diarrhea, anorexia, dehydration, edema and rash. A high rate of venous thromboembolism (VTE) was seen in all arms, highest in Arm A (Arm A 45 % versus 14 % [p=0.11])
Conclusion:
SEL+PEM-C is associated with higher, but less durable ORR. In this small study, PFS is numerically prolonged adding SEL to PEM-C with expected additive toxicity. Further exploration of these intriguing results is ongoing.
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.09-007 - Thoracic Asymmetry and Its Impact on Survival after Radiation and Surgery for Malignant Pleural Mesothelioma (ID 9086)
09:30 - 09:30 | Author(s): Penelope Bradbury
- Abstract
Background:
Staging for malignant pleural mesothelioma (MPM) remains a challenge due to poor prognostic utility. Other clinical factors may improve and refine the staging system. We investigate the impact thoracic asymmetry at time of initial presentation prior to therapy on survival in MPM patients treated with multimodal therapy.
Method:
We reviewed 93 consecutive treatment naïve MPM patients treated with Surgery for Mesothelioma after Radiation Therapy (SMART protocol) from Sep 2008 to Jul 2015. The right and left axial thoracic areas (defined as the product of the ant-post and med-lat extent of hemithoraces at the level of carina) were used to calculate the asymmetric thoracic ratio (ATR, where 1 is more symmetric, Figure 1). Significant factors were determined using univariate (log rank), multivariate (Cox proportional hazards) as well as recursive partition analysis (RPA). Continuous variables were discretized into binary categories split by its median value.
Result:
After a median follow-up of 15.6 months, 63 (68%) patients recurred, 56 (60%) died. The median ATR was 0.85, ranging from 0.52 to 1.00. On univariate analysis, histology (p=0.003 and 0.0002), gross tumour volume (GTV, p=0.004 and 0.001), and ATR (p=0.00001 and 0.0000002) all significantly impacted both overall and disease free survival, respectively, while mediastinal nodal involvement (p=0.03) was significantly associated with DFS only. On multivariate analysis, histology (p=0.01 and 0.005) and GTV (p=0.02 and 0.016) significantly impacted both overall and disease free survival, respectively. ATR significantly impacted disease free survival (p=0.02, HR=0.06 95% CI 0.02-0.20) and was suggestive of a trend for overall survival (p=0.07). On RPA, ATR<0.848 was significantly (p<0.001) associated with poorer DFS.
Conclusion:
A low asymmetric ratio (ATR<0.848) is significantly associated with poorer outcomes, specifically disease free survival, and is independent of histology and tumor volume. Further study is needed to validate this parameter.
