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Huamao M Lin
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.15 - Real-world ALK Testing Trends and Patterns in Patients with Advanced NSCLC in the United States (ID 3333)
00:00 - 00:00 | Author(s): Huamao M Lin
- Abstract
Introduction
Patients whose lung cancers harbor anaplastic lymphoma kinase (ALK) rearrangements are sensitive to treatment with ALK tyrosine kinase inhibitors (TKIs). Several treatment guidelines recommend molecular testing to identify ALK-positive patients who are eligible for ALK TKI therapy. This study assessed real-world ALK testing patterns among community practices in the United States in patients with advanced non-small cell lung cancer (NSCLC) and explored treatments received prior to receiving test results in patients with ALK-positive NSCLC.
Methods
This retrospective analysis used data extracted from the Flatiron Health electronic health record-derived deidentified database. Patients ≥ 18 years old with a diagnosis of advanced NSCLC (clinical stage IIIB or IV as determined by pathologic and radiologic findings) and ≥ 2 clinic visits within the Flatiron Network between 01/01/2011 and 12/31/2019 were included.
Results
Overall, 60,025 patients with advanced NSCLC were identified, including 41,496 patients with non-squamous cell carcinoma and 15,291 patients with squamous cell carcinoma. Between 2011 and 2019, 36,691 (61.1%) patients with advanced NSCLC were ever tested for ALK by various diagnostic tests. Of these, 1,042 patients were ALK-positive. In patients with advanced NSCLC, ALK testing rates increased from 33.1% in 2011 to 73.0% in 2019. Considering histological subtype, ALK testing rates increased from 41.6% in 2011 to 81.6% in 2019 in patients with non-squamous cell carcinoma and from 13.6% in 2011 to 50.4% in 2019 in patients with squamous cell carcinoma. The proportion of ALK testing conducted by fluorescence in situ hybridization (FISH) declined from 68.3% in 2011 to 32.1% in 2019, while the use of next-generation sequencing (NGS) increased from < 1% in 2011 to 52.2% in 2019. Overall, tissue samples were most commonly used for testing (85.1%), followed by blood samples (13.5%), and the use of blood samples for ‘liquid biopsy’ increased from < 1% in 2011 to 28.2% in 2019. Among 983 patients who tested ALK-positive with a non-missing test result date, 24.7% of patients initiated therapy before receiving their first ALK-positive test results, with immuno-oncology (IO) therapies the most common treatments initiated since 2017. Among those who tested ALK-positive, the proportion of patients who started IO therapies before receiving ALK test results increased from 4.8% in 2016 to 17.8% in 2019. Median time from diagnosis of advanced NSCLC to first ALK-positive result date was 23 days. This included a laboratory turnaround time of 9 days from the date specimens were received by the laboratory to the test report date.
Conclusion
Over time, ALK testing rates have increased, reaching over 70.0% since 2017. There was increased use of NGS and a concurrent decrease in the use of FISH as the primary testing method. Despite this increase, over a quarter of patients with advanced NSCLC were not tested for ALK, indicating that many patients are not receiving recommended biomarker testing. Furthermore, 24.7% of patients who tested ALK-positive initiated therapy before receipt of ALK test results, which indicates that treatment decisions are sometimes being made in the absence of recommended biomarker data.
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OA04 - New Data from Rare EGFR Alterations (ID 223)
- Event: WCLC 2020
- Type: Oral
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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OA04.03 - Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations (ID 3186)
11:45 - 12:45 | Author(s): Huamao M Lin
- Abstract
- Presentation
Introduction
Mobocertinib is a potent first-in-class tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (EGFRex20ins) mutations. We report first results from the EXCLAIM extension cohort of a phase 1/2 study (NCT02716116) and results in patients with EGFRex20ins-mutant NSCLC who received prior platinum-based therapy from the dose-escalation/expansion parts of the study and the EXCLAIM extension cohort.
Methods
This 3-part, open-label, multicenter study included dose-escalation/expansion cohorts and the EXCLAIM extension cohort. Data are presented for all patients treated in EXCLAIM (N=96) and for platinum-pretreated patients from the dose-escalation/expansion cohorts (n=28) and from EXCLAIM (n=86); all received mobocertinib 160 mg orally QD. Enrolled patients had locally advanced/metastatic EGFRex20ins NSCLC, ECOG performance status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease. The primary endpoint is confirmed ORR assessed by IRC per RECIST v1.1.
Results
In EXCLAIM, 96 patients were enrolled and treated; median age, 59 years [range: 27–80]; female, 65%; Asian, 69%; ≥2 prior systemic anticancer lines, 49% (range: 1–4). Median time on treatment was 6.5 months (range: 0–14). Confirmed ORR was 23% (22/96; 95% CI: 15%–33%) per IRC and 32% (95% CI: 23%–43%) per investigator; median DoR (Kaplan-Meier estimates) was not mature; median PFS was 7.3 months. See Table. In the analysis of platinum-pretreated patients (n=114), median age, 60 years [range: 27–84]; female, 66%; Asian, 60%; ≥2 prior systemic anticancer lines, 59% (range: 1–7). Median time on treatment was 7 months (range: 0–31); 38 patients (33%) remained on treatment as of 29-May-2020. Confirmed ORR was 26% (30/114; 95% CI: 19%–35%) per IRC and 35% (40/114; 26%–45%) per investigator. Median PFS was 7.3 months: 12-month PFS rate was 33% (95% CI: 21%–47%). Responses were observed among all prespecified subgroups, including Asian/non-Asian patients and those with/without baseline stable brain metastases. The most common treatment-related adverse events (TRAEs; ≥30%): diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%); grade ≥3 TRAEs (≥5%): diarrhea (22%), anemia (5%), and dyspnea (5%). Nineteen patients (17%) discontinued due to AEs, most commonly diarrhea (4%) and nausea (4%). The safety profile observed in EXCLAIM was largely consistent with that observed in the platinum-pretreated population.
Conclusion
Mobocertinib demonstrated clinically meaningful benefit in previously treated patients with NSCLC and EGFRex20ins mutations, with a manageable safety profile.
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P11 - Health Services Research/Health Economics - Quality of Life (ID 123)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P11.03 - Importance of Capturing the Patient Experience of Overall Symptoms and HRQoL Impact in Patients With ALK+ NSCLC (ID 1619)
00:00 - 00:00 | Author(s): Huamao M Lin
- Abstract
Introduction
Non–small cell lung cancer (NSCLC) with the anaplastic lymphoma kinase-positive (ALK+) mutation is a rare subtype of NSCLC. Available treatments include several ALK inhibitor therapies (eg, crizotinib, alectinib, ceritinib, and brigatinib) with some showing health-related quality of life (HRQoL) benefits. HRQoL, including disease- and treatment-related symptoms and impacts, is a significant factor when making treatment decisions. However, qualitative research on HRQoL among ALK+ patients is limited. The aim of this study was to better understand the overall symptom experience and HRQoL impact from the perspective of ALK+ NSCLC patients.
Methods
Interviews with expert oncologists were conducted to provide the clinical perspective and guide patient interviews. Following approval by an independent review board, semi-structured qualitative interviews were conducted with NSCLC patients with epidermal growth factor receptor or ALK mutations who had been symptomatic in the past month. During interviews, patients described their symptoms and the related HRQoL impact.
Results
Six oncologists were interviewed, identifying NSCLC symptoms, particularly: shortness of breath (100%), fatigue (100%), cough (83%), pain (67%), and hemoptysis (67%). The most common impacts were anxiety (50%), depression (50%), and confusion/bewilderment surrounding the diagnosis (50%), as most patients were never smokers and younger.
A total of 36 NSCLC patients were interviewed, including 8 ALK+ patients (median age 48.5 years [28–53]; 50% female, median disease duration 2.8 years [0–7]). All ALK+ patients had received radiation, 87.5% had received chemotherapy, and 62.5% had received targeted therapy. The most commonly reported symptoms from ALK+ patients were shortness of breath (100%), phlegm/congestion (100%), pain (87.5%), feeling tired/fatigue (87.5%), weight loss (75%), cough, coughing blood, appetite loss, constipation, and diarrhea (all 62.5%). Patients described experiencing negative impacts on daily activities (87.5%), including household chores and the ability to do hobbies. Additionally, impacts on social, emotional (both 62.5%), and physical functioning (50%) were also commonly reported. The patient experience with the core symptoms of lung cancer (dyspnea, cough, and pain) among ALK+ NSCLC patients was similar across our sample, irrespective of mutation. This qualitative research also confirmed the selection of patient-reported outcome instruments to assess core concepts that best capture the patient experience of ALK+ patients in a clinical trial setting, including a recent clinical trial of brigatinib versus crizotinib in ALK+ NSCLC. In this clinical trial, patients on brigatinib showed significant HRQoL benefits compared with crizotinib in the most common symptoms or impacts reported in the current qualitative study, including fatigue, nausea and vomiting, appetite loss, constipation, as well as emotional, social functioning, and global health status/QoL.
Conclusion
Incorporation of the patient voice through direct patient engagement provided valuable in-depth insight about patient experience in ALK+ NSCLC. This qualitative research provided insights into the unmet needs and patient goals for treatment, which may then be measured in a clinical trial to demonstrate treatment benefit from the patient perspective. It is important to measure what matters most to patients to improve treatment decision-making.
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.31 - Trends in the Detection of EGFR Exon 20 Insertions in Patients with NSCLC in the US (ID 3334)
00:00 - 00:00 | Presenting Author(s): Huamao M Lin
- Abstract
Introduction
Epidermal growth factor receptor exon 20 insertions (EGFRex20ins) are an uncommon subset of EGFR-activating mutations that are associated with a lack of responsiveness to tyrosine kinase inhibitor (TKI) therapy. With the clinical development of TKIs and monoclonal antibodies targeting EGFRex20ins, broad molecular profiling is needed to direct patients to these therapies. We describe real-world EGFRex20ins detection patterns in patients with advanced non-small cell lung cancer (NSCLC) in the United States.
Methods
Data were extracted from the Flatiron Health electronic health record-derived deidentified database. Patients ≥ 18 years, diagnosed with advanced NSCLC, and ≥ 2 clinic visits between 01/01/2011 and 12/31/2019 were included.
Results
A total of 60,025 patients with advanced NSCLC were identified 38,990 patients (65%) were tested for EGFR mutations, of which 326 (0.8%) harbored an EGFRex20ins; clinicopathologic characteristics of patients with an EGFRex20ins were similar to the canonical EGFR mutations. The frequency of EGFRex20ins among all NSCLC cases tested (by year of advanced diagnosis) increased from 0.6% in 2011 to 1.2% in 2019. In patients with an EGFRex20ins-positive result, the proportion of testing conducted by polymerase chain reaction (PCR) declined from 67% in 2011 to 16% in 2019, and use of next-generation sequencing (NGS) increased from 0% in 2011 to 64% in 2019. In EGFRex20ins-positive patients, tissue samples were most commonly used for testing (83%), while blood samples were also used (16%). Treatment was initiated in 26% of patients prior to confirmation of the first EGFRex20ins-positive result and in 2019, the most common treatment was immunotherapy-based (55.6%). The median time from advanced diagnosis to first EGFRex20ins result was 25 days, including a laboratory turnaround time of 10 days.
Conclusion
The detection rate of EGFRex20ins in NSCLC patients has increased, coinciding with a shift in testing methods from PCR to NGS. However, a notable proportion of patients initiated therapy before receipt of test results. With the development of EGFRex20ins targeted therapy, there is a need for early and broad biomarker testing.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.08 - First-line Brigatinib in Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer: A Network Meta-Analysis (ID 3330)
00:00 - 00:00 | Presenting Author(s): Huamao M Lin
- Abstract
Introduction
Anaplastic Lymphoma Kinase (ALK)-targeted tyrosine kinase inhibitors have shown to be effective as first-line (1L) treatment of ALK-positive non-small cell lung cancer (NCSLC). However, head-to-head comparisons between most available ALK inhibitors are lacking. The objective of this study was to conduct a systematic literature review (SLR) and meta-analyses to estimate the relative efficacy of brigatinib compared to other approved ALK inhibitors or chemotherapy in patients with locally advanced or metastatic ALK inhibitor-naïve ALK-positive NSCLC (≤1 prior chemotherapy regimen was allowed).
Methods
An SLR was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Searches (from inception to August 1, 2019) were performed in MEDLINE, Embase, the Cochrane Library and key conference proceedings (2016-2019) to identify relevant phase II or III randomized controlled trials (RCTs) in ALK inhibitor-naïve ALK-positive NSCLC patients. Bayesian network meta-analyses (NMAs) and Bucher indirect treatment comparisons (ITCs) were performed using fixed and random effects models to assess the comparative efficacy and safety of brigatinib with other ALK inhibitors or chemotherapy as 1L treatment.
Results
The SLR identified 8 RCTs assessing alectinib, brigatinib, ceritinib, crizotinib, and chemotherapy in the 1L setting, of which 5 global trials (ALEX, ALTA-1L, ASCEND-4, PROFILE 1007, PROFILE 1014) were included. The base-case, fixed effects results demonstrated that brigatinib significantly reduced the risk of disease progression or death (independent review committee [IRC]-assessed progression-free survival [PFS]) compared with ceritinib (HR, 0.42; 95% confidence interval [CI], 0.26-0.67), crizotinib (HR, 0.49; 95% CI, 0.35-0.68), and chemotherapy (HR, 0.23; 95% CI, 0.16-0.34). No significant differences were observed between brigatinib and alectinib in IRC-assessed (HR, 0.98; 95% CI, 0.61-1.57) or investigator-assessed PFS (HR, 1.01; 95% CI, 0.64-1.58) for overall patients, and in investigator-assessed PFS (HR, 0.63 95% CI, 0.28-1.42) for the subgroup with baseline CNS metastases. There were also no significant differences between brigatinib and all comparators for overall survival. Subgroup analyses of patients who had not received prior chemotherapy yielded similar results (Table 1).
Conclusion
Brigatinib significantly prolonged PFS in ALK inhibitor-naïve patients with ALK-positive NSCLC compared with ceritinib, crizotinib, and chemotherapy and was at least as effective as alectinib in reducing the risk of progression, suggesting that brigatinib is an effective 1L treatment. The results also suggest strong efficacy of brigatinib in patients with CNS metastases.
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P84.11 - Real-World Brigatinib Dosing Patterns in Patients with Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer in the United States (ID 3486)
00:00 - 00:00 | Presenting Author(s): Huamao M Lin
- Abstract
Introduction
Standard dosing of brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for treating ALK+ non-small cell lung cancer is 90 mg once daily for 7 days then escalated to 180 mg on Day 8 as tolerated. Among patients receiving this standard dose, 29% in the post-crizotinib ALTA trial and 38% in the tyrosine kinase inhibitor (TKI)-naïve ALTA-1L trial required a dose reduction. Asymptomatic laboratory abnormalities including creatine phosphokinase, amylase or lipase elevations were common causes of dose reductions in these studies. Outside of trial protocol mandated dosing, real-world dosing patterns of brigatinib have not been previously described.
Methods
Adult (≥18 years) patients with ≥1 claim for brigatinib were identified between 01 April 2017 and 31 August 2019 from the IQVIA longitudinal pharmacy claims database and followed until the earliest of: dose reduction, treatment discontinuation, or end of follow-up. Average daily dose (ADD) was calculated as the product of pill strength and quantity of pills dispensed divided by the day supply. Dose reduction was defined as ≥30 days of supply with ADD < 180 mg/day after reaching 180 mg/day, or < maximum (max) dose in patients who did not reach 180 mg/day. Time to dose reduction from 180 mg/day or max dose and probability of continued therapy at ≥180 mg/day or max dose were assessed via Kaplan-Meier analysis. Adherence was defined using medication possession ratio (MPR) and dose compliance score (DCS) was calculated as total dosage received divided by total dosage expected.
Results
A total of 240 brigatinib patients were identified. Median age was 58 years, 57.9% were female and 85.4% had ≥1 prior TKI. Mean (standard deviation) follow-up time was 10.7 (7.6) months. A dose of 180 mg/day was achieved in 202 (84.2%) patients, of which 87.1% were treated after 1+ prior lines. Dose reduction occurred in 15.8% of patients who reached 180 mg/day, and the probability of continued therapy at ≥180 mg/day in patients still on therapy at 3 and 6 months after dose escalation was 89.5% and 86.0%, respectively. Of the patients with dose reduction, 43.8% reduced to 120 mg/day. A total of 38 (15.8%) patients did not reach 180 mg/day. Dose reduction occurred in 13.2% of these patients, and the probability of continued therapy at the max dose at 3 and 6 months after max dose was reached was 94.1% and 89.8%, respectively. Among the patients with dose reduction, 40.0% reduced to 90 mg/day. Adherence and dose compliance were high overall with 93.3% of patients having MPR > 80% and median DCS of 1.0 (0.3-2.2).
Conclusion
Real-world data suggest that standard dose escalation (90 to 180 mg) occurs in most brigatinib patients (>84%) and that dose reduction rates may be lower outside the protocol mandated confines of clinical trials. Adherence and dose compliance were high. Analysis with longer follow-up time may be warranted to further evaluate these findings.
