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Åslaug Helland
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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-12 - The Neutrophil and Platelet to Lymphocyte Ratios and Glasgow Prognostic Score as a Predictor for Relapse After Stereotactic Radiation for Lung Cancer (Now Available) (ID 440)
08:00 - 18:00 | Author(s): Åslaug Helland
- Abstract
Background
Chronic inflammation plays an important role in lung carcinogenesis. The neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte ratios (PLR) and modified Glasgow Prognostic Score (mGPS) have been associated with overall mortality and PLR greater than 250 with non-local failures in non-small cell lung cancer (NSCLC) patients. We hypothesised that NLR, PLR and mGPS were higher in patients developing non-local failures within the first year after stereotactic body radiation therapy (SBRT) than in those without non-local failures.
Method
Medically inoperable stage I NSCLC patients were included in a prospective, observational, single centre study from February 2014 until December 2017. Follow up included physical examination, CT scans and blood samples at baseline, 6 weeks, 3, 6, 9 and 12 months after SBRT. Most patients took baseline blood samples within mean 7 days before treatment. Differences in NLP, PLR and mGPS between the groups (with and without non-local failures) were calculated using Mann-Whitney-Wilcoxon U-test.
Result
We included 46 patients with median age 75 years, of which 67% were men. Comorbidities were common, and 80% had chronic obstructive pulmonary disease (COPD). Six patients were diagnosed with non-local failures within the first year of follow-up. Multiple metastases were identified in the mediastinum (2 patients), contralateral lung (2 patients) and in the liver and bone (2 patients).
ConclusionMarker
Non-local failures (n=6)
Without non-local failures (n=40)
P-value
NLR
3.3
3.5
0.83
PLR
246
158
0.35
mGPS
0.67
0.33
0.27
Our study found no statistically significant association between increased NLR, PLR, mGPS and the identification of non-local failures within the first year after SBRT. This is a relatively small cohort of patients, and the patients suffered from serious chronic medical comorbidities such as COPD, chronical renal and cardiac disease. These medical conditions can also influence NLR, PLR, mGPS and can explain our finding.
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.06 - Efficacy Results of Selective AXL Inhibitor Bemcentinib with Pembrolizumab Following Chemotherapy in Patients with NSCLC (Now Available) (ID 2271)
10:30 - 12:00 | Author(s): Åslaug Helland
- Abstract
- Presentation
Background
The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.
Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.
Method
This phase II trial (Cohort A, NCT03184571) enrolled 48 advanced lung adenocarcinoma patients with progression on or after no more than one prior line of platinum-based chemotherapy. Patients with EGFR/ALK mutations were included in this study and must have progressed on or after at least one standard targeted therapy. The primary endpoint was ORR according to RECIST v1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS, and safety. Tumour biopsies were analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.
Result
As of April 2019, the trial was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers.
At time of writing, a total of 210 treatment cycles had been completed by all patients. 17 patients were ongoing.
17 of 32 biomarker-evaluable patients (53%) were PD-L1 negative, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Of 28 biomarker-evaluable patients, 14 (50%) expressed AXL on their tumours.
Among patients who had at least 1 evaluable on-treatment scan: 5 responses were observed in 13 AXL positive patients (38%), and 7 in 30 patients with TPS 0-49% (23%). There were 10 responses observed among 34 evaluable patients overall (29%).
In Stage 1, two of the 4 AXL positive responses are ongoing; mDoR is not mature in the AXL positive patients. mPFS was 5.9 mo in AXL positive patients (n=10, 3.0-NR) and 4.0 mo (95% CI 1.9-NR) overall (n=24). mOS was not mature.
The most common TRAEs (occurring in >10% of patient in both stages) were transaminase increases (34%), asthenia/fatigue (30%), diarrhoea (26%), nausea (13%), anaemia (11%), decreased appetite (11%), and pruritus (11%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments.
Conclusion
Patients had predominantly low or no PD-L1 expression; approximately half were AXL positive. The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients, particularly in those with AXL positive disease, including PD-L1 negative patients. Mature ORR for both stages, as well as 12-month OS for stage 1 will be presented at the meeting.
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OA02 - A New Vision of Targets and Strategies (ID 120)
- Event: WCLC 2019
- Type: Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Frank Griesinger, Luis Paz-Ares
- Coordinates: 9/08/2019, 10:30 - 12:00, Seoul (2007)
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OA02.07 - Phase 3 ALUR Study of Alectinib in Pretreated ALK+ NSCLC: Final Efficacy, Safety and Targeted Genomic Sequencing Analyses (Now Available) (ID 2267)
10:30 - 12:00 | Author(s): Åslaug Helland
- Abstract
- Presentation
Background
The ALUR (NCT02604342) primary analysis (cut-off January 2017) demonstrated improved efficacy and safety with alectinib versus chemotherapy in patients with ALK+ NSCLC previously treated with chemotherapy and crizotinib. These patients can develop crizotinib resistance through ALK secondary mutations, but limited data exist regarding alectinib’s efficacy in patients with different post-crizotinib genetic profiles. We report final data from ALUR including treatment outcomes according to genetic profile.
Method
Overall, 119 patients with locally determined ALK+ NSCLC were randomised 2:1 to receive alectinib 600mg bid or chemotherapy (pemetrexed 500mg/m2 or docetaxel 75mg/m2 q3w). The primary endpoint was PFS by investigator. Targeted genomic sequencing (FoundationONE® [tissue; 315 genes] and FoundationACT® [plasma; 62 genes]) was performed retrospectively using tumour tissue (n=33) and baseline plasma (n=59).
Result
Final efficacy data confirmed those of the primary analysis (table). Grade ≥3 treatment-emergent adverse events were lower with alectinib (37.7%) than with chemotherapy (43.2%); adverse events causing treatment discontinuation were lower with alectinib (5.2% versus 10.8% chemotherapy), despite alectinib’s longer treatment duration. ALK fusions were confirmed retrospectively in 26/33 (78.8%) tissue and 41/59 (69.5%) plasma (post-crizotinib) samples. ORR in alectinib-treated patients with ALK fusions was 72.2% (13/18, tissue) and 63.0% (17/27, plasma) versus 0% for chemotherapy (tissue [0/8], plasma [0/14]). ALK secondary mutations were detected in 16/59 (27.1%) patients (plasma, both arms). ORR in the alectinib arm (plasma) was similar in patients with ALK fusions with (60.0%, 6/10) or without (64.7%, 11/17) ALK secondary mutations, but lower in patients with gene mutations other than ALK (23.1%, 3/13).
Conclusion
Final data from ALUR confirm the primary analysis, demonstrating improved efficacy and safety with alectinib versus chemotherapy in post-crizotinib ALK+ NSCLC. The role of reconfirming ALK status upon sequential ALK inhibitor treatment requires further investigation, due to the limited data and known technical challenges of plasma testing.
Funding: F. Hoffmann-La Roche Ltd.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-72 - A Phase II Study of Selective AXL Inhibitor Bemcentinib and Pembrolizumab in Patients with NSCLC Refractory to Anti-PD(L)1 (ID 1632)
09:45 - 18:00 | Author(s): Åslaug Helland
- Abstract
Background
The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.
Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.
The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients (Cohort A, NCT03184571), particularly in those with AXL positive disease, including PD-L1 negative patients.
The novel combination is now being assessed in patients refractory to anti-PD-(L)1 therapy, considering the emerging need in this population and AXL’s role as a mediator of resistance.
Method
This is an open-label, single-arm, 2-stage phase II study (Cohort B, NCT03184571) to evaluate the safety and efficacy of bemcentinib (200mg/d) in combination with pembrolizumab (200mg/q3wk) in patients post anti-PD-(L)1 therapy. The primary endpoint is overall response rate (ORR), and additional endpoints include efficacy by biomarker expression, duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. Clinical efficacy endpoints are based on tumour imaging evaluable by RECIST v1.1.
Eligible patients received a maximum of 2 prior lines of therapy, with the most recent course having included a PD-(L)1 inhibitor. To be eligible, patients must have exhibited disease control (CR/PR/SD) for at least 6 months on prior PD-(L)1 inhibitor therapy with disease progression occurring within 12 weeks since last dose.
Bemcentinib will be administered as a loading dose of 400mg on days 1, 2 and 3 followed by a dose of 200mg once daily. A fixed dose of 200 mg pembrolizumab will be given by intravenous infusion over 30 minutes every 3 weeks. Bemcentinib and pembrolizumab will be given until disease progression, unacceptable dose toxicity, or for a maximum of 35 cycles.
Tumour specimens will be analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.
The pre-specified efficacy threshold for continuation into the second stage is 1 objective response among the first 13 patients, at which point up to a further 16 patients may be evaluated, for a total of 29 patients.
Result
Section not applicable
Conclusion
Section not applicable
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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
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-74 - Radiotherapy Prior to Immunotherapy Is Associated with Durable Disease Control in Advanced NSCLC (ID 1581)
10:15 - 18:15 | Author(s): Åslaug Helland
- Abstract
Background
In an unselected patient cohort response rates for immune checkpoint inhibitors in advanced NSCLC are around 20 %1-3. To enhance this proportion several treatment combinations are under investigation. Radiotherapy combined with immunotherapy has shown promising results in preclinical trials and clinical trials using this combination are in progress, assessing safety and optimal dosage/timing of radiotherapy4.
Method
Between May and September 2015 fifty-seven patients with advanced NSCLC were treated with nivolumab (3 mg/kg every 2nd week) at The Norwegian Radium Hospital in a named-patient-use-program. Clinical information, including dosage and timing of radiotherapy given prior to immunotherapy, has been collected and correlated to clinical outcome.
Result
Conclusion
Median follow-up time for those with no event when data was collected was 43.4 months (range 42.4-44.1 months) and overall survival 14%. Eight patients died of other causes than lung cancer. Radiotherapy administered at different time intervals before the first dose of nivolumab was correlated to progression free survival (PFS) and overall survival (OS) using cox regression analysis. We found poor PFS (HR 3.1 p=0.034) and OS (HR 3.7 p=0.015) for those who received radiotherapy between 1-2 months prior to nivolumab. The indication for radiotherapy in late stage lung cancer is most often symptomatic metastases. Hence, recent radiotherapy is usually associated with more advanced disease and poor prognosis. When patients were divided into groups according to prognosis we found that many in the group with short PFS had received radiotherapy shortly before immunotherapy but the proportion was even higher in the group with durable response (figure 1).
Our findings support the hypothesis that radiotherapy can trigger a tumor-directed immune response which can be enhanced by immunotherapy and result in long-lasting disease control. We will validate our results in an additional cohort and will assess and include PD-L1 expression in our analysis.
1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015;373(2):123-35.
2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015;373(17):1627-39.
3. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372(21):2018-28.
4. Ngwa W, Irabor OC, Schoenfeld JD, et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018;18(5):313-22.
