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Ross Soo
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MS28 - IO Combinations in Advanced NSCLC (ID 806)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 106
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MS28.04 - Combination with Targeted Therapies (ID 11523)
14:15 - 14:30 | Presenting Author(s): Ross Soo
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-21 - Safety of Durvalumab Retreatment in Advanced NSCLC Patients Who Progressed Following Initial Disease Control In ATLANTIC (ID 12386)
16:45 - 18:00 | Author(s): Ross Soo
- Abstract
Background
In ATLANTIC, patients who completed a year of durvalumab (anti-PD-L1) treatment but later progressed off therapy were eligible for retreatment. We evaluated safety in these patients compared with the overall study population.
a9ded1e5ce5d75814730bb4caaf49419 Method
ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in patients with Stage IIIB–IV NSCLC who had received ≥2 prior systemic treatment regimens, including one platinum-based. The study included three independent cohorts. In C1 (EGFR+/ALK+) and C2 (EGFR−/ALK−), enrollment was enriched for patients with ≥25% of tumor cells (TC) expressing PD-L1, while patients in C3 (EGFR−/ALK−) only had PD-L1 TC ≥90%. Patients received durvalumab 10 mg/kg q2w for ≤12 months. Patients who achieved and maintained disease control but then progressed after completing the initial 12-month treatment period were offered retreatment for a maximum of 12 months of further treatment. Safety and tolerability was a secondary outcome.
4c3880bb027f159e801041b1021e88e8 Result
As of November 7, 2017, of 442 patients in the ATLANTIC full analysis set, 102 (23.1%) had completed 12 months of initial treatment and 95 (21.5%) had disease control at the end of initial treatment. A total of 40 patients started retreatment. The median actual duration of exposure to durvalumab was 16.0 weeks (range 1–62; 40.1% of patients on treatment for ≥24 weeks) during initial treatment and 18.1 weeks (range 2–52; 37.5% of patients on retreatment for ≥24 weeks) during retreatment. The table shows safety during initial treatment and retreatment.
8eea62084ca7e541d918e823422bd82e ConclusionInitial treatment (n=444)
Retreatment phase (n=40)
Cohort,* n (%)
C1 (EGFR+/ALK+)
111 (25.0)
7 (17.5)
C2 (EGFR−/ALK−)
265 (59.7)
26 (65.0)
C3 (EGFR−/ALK−; TC ≥90%)
68 (15.3)
7 (17.5)
Any TRAE, n (%)
256 (57.7)
19 (47.5)
Grade ≥3 TRAEs
42 (9.5)
6 (15.0)
TRAEs leading to death
0
2 (5.0)†
Serious TRAEs
28 (6.3)
4 (10.0)
TRAEs leading to discontinuation
10 (2.3)
4 (10.0)
Safety analysis set. *A more detailed analysis of exposure and safety by cohort will be presented. †Causes of death were: pneumonitis and respiratory failure; cardiac arrest. TRAE=treatment-related adverse event.
A large proportion of patients (37.5%) maintained retreatment for ≥24 weeks, suggesting that patients who originally completed 12 months of treatment can tolerate sustained retreatment. The tolerability profile of durvalumab upon retreatment was similar to that seen during initial treatment, although there were two treatment-related deaths during the retreatment phase. Retreatment with anti-PD-L1 may be feasible for selected patients with NSCLC who demonstrate original benefit and progress off therapy.
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P1.01-28 - Impact of Afatinib Dosing on Safety and Efficacy Real-World in Patients with EGFR Mutation-Positive Advanced NSCLC (ID 13276)
16:45 - 18:00 | Author(s): Ross Soo
- Abstract
Background
Tolerability-guided dose adjustment of afatinib reduced incidence and severity of adverse drug reactions (ADRs) without affecting efficacy in the LUX-Lung (LL) studies in patients with EGFR mutation-positive (EGFRm+) NSCLC. We evaluated the impact of modifying the recommended starting dose of afatinib (40mg) on efficacy and safety in a real-world setting.
a9ded1e5ce5d75814730bb4caaf49419 Method
This non-interventional, observational, multi-country/site study used medical records of TKI-naïve patients with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib. Primary outcomes were % patients with ADRs by severity, time on treatment (TT), and time to progression (TTP), relative to LL3. Secondary outcomes were % of patients with/reasons for modified starting dose.
4c3880bb027f159e801041b1021e88e8 Result
228 patients from 13 countries were included. Baseline characteristics were generally similar to LL3, but with more Del19 patients (78% vs 49%) and fewer Asian patients (44% vs 72%); 12% had ECOG PS 2–3. 31% of patients received an afatinib starting dose of <40 mg; 20% of patients starting with <40 mg increased their dose during the study. 67% of 40 mg starters underwent dose reductions, with 86% of those occurring in the first 6 months. Dose reductions were more frequent in females, Eastern Asian patients, and those with lower body weight. The main reason for dose modification was ADRs. In <40 mg starters, overall ADR incidence was similar to that in ≥40 mg starters, with fewer G3 (17% vs 25%) and no G4 ADRs. There were no new safety signals, and fewer ≥G3 ADRs and serious adverse events (SAEs) than in LL3 (28% vs 49% and 5% vs 14%, respectively). >60% of patients received medications to treat diarrhea and manage skin AEs. Median TT and TTP were 18.7 months and 20.8 months, respectively, and were not impacted by reduced starting dose or dose modification (19.4/17.7/19.5 and 25.9/20.0/29.0 months for patients who started on ≤30 mg/reduced to <40 mg/remained on ≥40 mg, respectively). The efficacy of afatinib was demonstrated across all patient subgroups analysed (ECOG PS 0/1 vs 2/3, age <75 yrs vs ≥75 yrs, EGFR mutational status); TT and TTP were significantly longer in patients with ECOG PS0/1 versus PS2/3.
8eea62084ca7e541d918e823422bd82e Conclusion
As in pivotal trials, dose adjustments with afatinib in real-world practice reduced the frequency and intensity of ADRs without impacting efficacy. RealGido demonstrated long TT/TTP regardless of afatinib dose adjustment or reduced starting dose, and an acceptable safety profile. The results highlight the benefit of tailoring afatinib dose based on individual patient characteristics and ADRs to optimize outcomes.
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P1.01-38 - A Phase II With a Lead-In Phase I Study to Examine Safety and Efficacy of Hydroxychloroquine and Gefitinib in Advanced NSCLC (ID 11325)
16:45 - 18:00 | Author(s): Ross Soo
- Abstract
Background
Tyrosine kinase inhibitors (TKIs) benefit advanced non-small cell lung cancer (NSCLC) patients that harbor epidermal growth factor receptor (EGFR) mutations, but resistance invariably develops. Preclinical work demonstrated re-sensitization to EGFR-TKIs in cells with acquired resistance, and increased sensitivity of EGFR-mutant cells to erlotinib and hydroxychloroquine (HCQ) combination. We examine the safety and efficacy of HCQ with gefitinib in an Asian cohort of NSCLC patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We enrolled stage IIIB/IV lung adenocarcinomas with sensitizing EGFR mutations. In the early phase of the study, non-smokers with unknown EGFR status were allowed. In the phase I lead-in study (Nov 2008-Jan 2010), maximum tolerable dose (MTD) of HCQ and gefitinib was ascertained via a 3+3 dose escalation schema.
In the phase II single-arm study (March 2010-May 2016), all patients were treated with gefitinib 250mg om and MTD (600mg om) of HCQ, and stratified into TKI-naïve and TKI-treated cohorts. In the TKI-treated cohort, patients must have prior response to gefitinib for more than 12 weeks and developed resistance. Primary end point (PEP) in the TKI-naïve cohort was objective response rates (ORR) and progression-free survival (PFS). In the TKI-treated cohort, PEP was ORR, and to determine if combination treatment can re-sensitize acquired resistance to EGFR TKIs.
4c3880bb027f159e801041b1021e88e8 Result
75 patients were treated. EGFR mutations were identified in 77.3%. In the phase I cohort (n=13), MTD of HCQ was 600mg. HCQ-gefitinib combination was well tolerated. Common adverse events were rash and diarrhea, mainly from gefitinib. There was no dose-limiting toxicity. In TKI-naïve cohort (n=37) of the phase II study, ORR was 75.8% (95% CI 57.7-88.9). Median PFS was 9.4 months (95% CI 6.8-12.0). Four patients who were non-evaluable had early toxicities, including pneumonitis and hepatitis flare. In the TKI-treated cohort (n=25), 52% had received 2 or more lines of prior treatment. Disease control rate with TKI re-challenge was 50% (95% CI 21.9-70.9), ORR was 4.2% (95% CI 0.1-21.1). Median PFS was 2.4 months, and median overall survival was 9.9 months (95% CI 5.7-14.0). Three patients achieved a progression-free interval of more than 7 months after re-challenge (7.6; 11.2; 15.9 months).
8eea62084ca7e541d918e823422bd82e Conclusion
Combination of HCQ-gefitinib is safe. In the TKI-naïve cohort, combination treatment did not improve PFS over reported average of 10 months for 1st-generation EGFR TKIs. However, in the TKI-treated cohort, re-responses and disease control to 1st-generation EGFR TKIs were seen, suggesting either a re-treatment effect or disease stabilization with addition of HCQ in acquired EGFR resistance.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-27 - Development, Internal Validation, and Calibration of a Risk Score to Predict Survival in Patients with EGFR Mutant NSCLC (ID 13610)
16:45 - 18:00 | Presenting Author(s): Ross Soo
- Abstract
Background
The emergence of molecularly targeted therapy has transformed the clinical landscape of metastatic non-small cell lung cancer (NSCLC). We profiled a local cohort of EGFR mutation-positive, advanced NSCLC patients who were treated with first-line EGFR tyrosine kinase inhibitors (TKIs) and sought to develop a nomogram-based prognostic model for predicting clinical outcomes in this patient subgroup.
a9ded1e5ce5d75814730bb4caaf49419 Method
A cohort of 199 EGFR mutation-positive, advanced NSCLC patients was retrospectively analyzed, with the inclusion criteria as follows: at least one sensitizing EGFR mutation, diagnosed with metastatic disease at diagnosis or incurable disease recurrence, and subsequently treated with first-line EGFR TKI for at least one-month duration. The Mnet machine learning algorithm was used to select variables for inclusion into the Cox model, with an alpha of 0.06 and gamma of 3. Internal validation was performed by plotting the bootstrapped (n = 200 bootstrap samples) time-dependent AUC according to the method described in Uno et al. (2007), and the predictive power of the model was assessed by computing Harrell’s C and Somers’ D concordance statistics. Internal calibration was evaluated using a plotted graph of observed vs predicted mortality risks of five risk groups (“low risk”, “medium-low risk”, “medium risk”, “medium-high risk”, and “high risk” quintiles), as well as the Kaplan-Meier survival estimates for each quintile.
4c3880bb027f159e801041b1021e88e8 Result
The resultant prognostic nomogram included the following variables - total white blood cell (WBC) count, hemoglobin levels, serum LDH levels, Neutrophil/Lymphocyte Ratio (NLR), ethnicity (Chinese vs non-Chinese), Karnofsky-Performance Status (score of ‘90-100’ or ‘70-80’ vs ‘0-60’), Charlson Comorbidity Index (≥3, 2, or 1 vs 0), neurological symptoms, brain, lung/pleural and adrenal metastases. The time-dependent AUC at 6, 12 and 18 months were 62.8%, 65.5%, and 67.4% respectively and the Harrell’s C and Somers’ D concordances were 0.6342 and 0.2684 respectively. The 12-month observed vs predicted overall survival (OS) probabilities were 0.56 vs 0.61, 0.64 vs 0.66, 0.55 vs 0.69, 0.77 vs 0.71, and 0.87 vs 0.73 respectively for each of the five risk groups described earlier, suggesting good calibration. Survival curves for the five risk groups also segregated well on visual inspection, and was corroborated by log-rank P < 0.001.
8eea62084ca7e541d918e823422bd82e Conclusion
We herein report a novel nomogram-based risk scoring system that incorporates biochemical, immune and clinical variables to provide fairly robust OS estimation in EGFR mutation-positive, advanced NSCLC patients treated with first-line EGFR TKIs.
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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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PL02.10 - Discussant - PL02.09 (ID 14740)
09:25 - 09:30 | Presenting Author(s): Ross Soo
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
