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Clare Senko
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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-14 - The Prognostic Significance of Significant Weight Loss in Stage III NSCLC Undergoing Definitive CRT After FDG-PET Staging (Now Available) (ID 589)
09:45 - 18:00 | Presenting Author(s): Clare Senko
- Abstract
Background
In the pre-PET era, weight loss is a harbinger of occult metastatic disease in patients with stage III NSCLC. Identifying the relationship between weight loss and pattern of relapse (POR), may enable stratification of patients into prognostic groups associated with increased risk of relapse. We sought to identify if weight loss remains a negative independent prognostic factor after FDG-PET staging.
Method
A retrospective audit (using web-based and electronic databases) was conducted in all patients with stage III NSCLC treated with definitive CRT between 01/07/2013 and 30/06/2018 at the Royal Brisbane and Women's Hospital and The Prince Charles Hospital, Queensland, Australia. A descriptive analysis was applied to describe the primary end-point of PFS and secondary end-points of OS and POR, in relation to the percentage of pre-treatment weight loss (0-10% vs >10-20% vs >20%). A subset analysis looked at other prognostic factors identified in NSCLC to account for potential confounders.
Result
Of the 127 patients (mean age 65 years, mean weight 76kg, 57% male, 42% current smokers) who commenced treatment during the study period, 24% lost > 10% and 3% lost > 20% weight. Median TTP for the entire cohort was 9 months. Based on multivariable modelling, risk of PD or death was 45% higher with > 10% loss of body weight (p=0.004), and risk of death was 36% higher with > 10% loss of body weight (p=0.05). Of the 54% that died during follow-up, 31 had distant PD, 18 had locoregional PD, 6 had local PD, and 10 had no PD. Males were at increased risk of PD.
Conclusion
A prognostic link continues to be identified between significant (> 10%) weight loss and risk of progressive disease or death in stage III NSCLC treated with definitive CRT despite pre-treatment FDG-PET. These findings identify a sub-group of patients where weight loss could still be a surrogate for micro-metastases not detected on PET, or other adverse prognostic markers. Other treatment strategies or improved diagnostic strategies are warranted.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-11 - Overcoming Resistance to Immunotherapy Using CVA21: Initial Results from a Phase II Study (Now Available) (ID 2070)
10:15 - 18:15 | Presenting Author(s): Clare Senko
- Abstract
Background
Resistance develops in most non-small cell lung (NSCLC) patients treated with anti-PD-1/anti-PD-L1 based immunotherapy. CVA21 is an oncolytic coxsackie virus that targets ICAM over-expressing tumour cells. Pre-clinical models suggest that CVA21-induced tumour lysis may enhance the clinical efficacy of the anti-PD-1 antibody Pembrolizumab by inducing immune cell infiltration in patients that lack an immune cell rich tumour microenvironment. Previously, the Keynote 200 trial of CVA21 combined with Pembrolizumab reported an ORR of 23% in immunotherapy-naive NSCLC. We report the efficacy of Pembrolizumab in combination with CVA21 in a preliminary cohort of eight pre-treated NSCLC patients with secondary resistance to prior anti-PD-1/anti-PD-L1 therapy.
Method
On progression of prior therapy, IV CVA21 (1x109 TCID50) was administered on days 1, 3, 5, 8, then Q3W for 6 months, in combination with Pembrolizumab (200mg IV from day 8, then Q3W for up to 24 months). Repeat biopsies were mandated prior to cycle 2 of Pembrolizumab. Tumour measurements were calculated using immune-related RECIST. PD-L1 was tested on pre- and post-treatment biopsies using SP-263 (Ventana) and reported using the tumour proportion score (TPS).
Result
The majority of patients were female (n=7, 88%), median age 65 years (range 55-75), seven (88%) current or former smokers, five (63%) with 3+ lines of prior treatment, and only 1 anti-PD-1/anti-PD-L1 naive. Two patients were KRAS mutant, the remaining were wild type for EGFR, ROS1, ALK and BRAF.
Two (25%) partial responses (PR) were observed, both in anti-PD-1/anti-PD-L1 pre-treated patients. Both responders were continuing at data cut-off, 240 and 120 days since commencement. Two achieved SD (overall clinical benefit 50%) and 3 were non-evaluable (1 early non-treatment-related death, 3 awaiting first scan). Early PD at 56 days occurred in the anti-PD-1/anti-PD-L1 naive patient (n=1).
In the two PRs, PD-L1 TPS was 25% and 60% respectively. Preliminary IHC staining of paired biopsies showed an increase in PD-L1% in 2 (33%) evaluable patients at 21 days. PD-L1 TPS ranged from <1% to 80% in pre-treatment biopsies, but was not predictive of response or benefit from combination therapy. An increase in PD-L1 was associated with a trend toward longer disease stability (median 147 days).
Combination treatment was well-tolerated with no observed G4/5 TRAE's.
Conclusion
Intravenous CVA21 in combination with pembrolizumab demonstrated encouraging clinical activity in patients who had progressed on prior anti-PD-1/anti-PD-L1 therapy, regardless of PD-L1 levels.
