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D. Tan
Moderator of
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OA16 - Improving the Quality of Lung Cancer Care - Patients Perspective (ID 399)
- Event: WCLC 2016
- Type: Oral Session
- Track: Patient Support and Advocacy Groups
- Presentations: 8
- Moderators:G. Kreye, D. Tan
- Coordinates: 12/06/2016, 16:00 - 17:30, Schubert 6
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OA16.01 - The Role of Patient Groups in Integrating the Patient Voice into Drug Funding Decisions (ID 4291)
16:00 - 17:30 | Author(s): C. Sit, H. Mai, A. Chambers, P. Wheatley-Price
- Abstract
- Presentation
Background:
The recent emergence of multiple new targeted therapies and immunotherapy drugs has significantly increased options in the systemic treatment of lung cancer (LC). While great news for patients, in the current environment of scarce health care resources, government agencies deliberating on public funding of cancer drugs struggle with ensuring sustainability of the public health system due to increasingly expensive drug costs. In Canada, the Pan-Canadian Oncology Drug Review (pCODR), a program of the Canadian Agency for Drugs and Technologies in Health (CADTH), provides recommendations that informs public funding decisions for cancer drugs. pCODR’s recommendations apply an evidence-based deliberative framework which considers the drugs clinical benefit, patient-based values, cost-effectiveness and adoption feasibility. As part of the pCODR review, patient input is integrated into the clinical and economic reports and recommendations. Patient groups, such as Lung Cancer Canada (LCC), can play a pivotal role by synthesizing the evidence gathered from patients and caregivers to inform the pCODR process.
Methods:
Both quantitative and qualitative techniques were used to gather data for LCC’s pCODR submissions. A national survey – the Faces of Lung Cancer (FOLC) - illustrated the perceptions and general unmet needs of those living with LC. Focus groups, one-on-one interviews and audits of patient discussion boards gathered the insights of patients and caregivers with experience on the drug under consideration. Patients were identified through LCC’s Medical Advisory Committee and their networks, clinical trial investigators, outreach to other patient groups and scans of LC patient/caregiver discussion boards.
Results:
Since 2014, LCC has made five pCODR submissions. 91 patients and 72 caregivers participated in the FOLC survey. The insights of an additional 62 patients and 38 caregivers with experience on the drugs under consideration were gathered qualitatively. LCC’s submissions describe the emotional, practical and logistical challenges of living with LC, and illustrate the “life impact” of the drug under consideration. - factors not traditionally included in clinical trial design.
Conclusion:
pCODR’s deliberative process, partnered with LCC’s methodology, may be an effective model to aid public funding discussions of new cancer drugs. pCODR and the reviewers have found patient group submissions valuable in providing lived-experience insight, at times changing perspectives. LCC’s contribution has been strongly reflected in the funding guidance reports. To supplement its process, pCODR recently launched a pilot project to include clinician input in the review process. The impact of the pilot will be assessed as data becomes available.
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OA16.02 - Shared Decision Making (SDM) and Patient Decision Aids (PDAs) in Lung Cancer: Survey of Patients, Significant Others or Caregivers (Abstract under Embargo until December 4, 7:00 CET) (ID 4767)
16:00 - 17:30 | Author(s): L. Gaspar, H.J. West, B.J. Addario, D..R. Camidge
- Abstract
- Presentation
Background:
Shared decision making (SDM) between the patient and their physicians is recognized as a desirable goal. When one treatment option is not clearly superior to another, PDAs can help present risks and benefits in a simple, visual format. Of the 600 plus validated PDAs, less than 60 of these are designed for cancer treatment decisions, and only 10 deal with lung cancer diagnosis or treatment (www.ohri.ca/decisionaid). A survey of lung cancer patients or their significant others/caregivers collected information regarding decision making experiences, and the perceived usefulness of PDAs.
Methods:
A survey (via SurveyMonkey) was sent to lung cancer patients/caregivers/significant others who had signed up for email communication from the Bonnie Addario Lung Cancer Foundation (ALCF), Global Resource for Advancing Cancer Education (GRACE), or the University of Colorado. The survey collected information regarding demographics, categorization of the difficult problem, and the sources of problems encountered during decision making. A PDA regarding prophylactic cranial irradiation (PCI) for limited small cell cancer was made available, and opinions were sought regarding the usefulness of this format.
Results:
190 responses were obtained (123 patients, 67 other). This was predominantly a well-educated, white, North American population, with advanced disease, with more women than men (75% vs 25%). 115 (61%) of respondents had faced a difficult decision, women more so than men. Decisions regarding systemic therapy were the most commonly perceived difficult decision (58%) and/or tests that were done/not done (34%). Sources of difficulty were identified as insufficient information (44%), or conflicting information or recommendations from their physicians (34%). The amount of information available was categorized as insufficient, just right, too much or difficult to know in 14%, 22%, 2%, 50%. Men were more likely to indicate that they had sufficient information, 39% vs 14%, p< 0.05. Most patients desired SDM, with only 9% expressing the desire to make the decision alone. However, 26% perceived that they had done so. Fortunately, only 8% of respondents expressed regret regarding their decision. Of 90 respondents who viewed the PCI PDA, 61% felt that this type of decision aid would have been helpful. There were no gender differences regarding opinions towards the PDA, the desire for SDM, or the perception that it had occurred.
Conclusion:
Lung cancer patients desire shared decision making. Improvements in this process are perceived as needed, possibly with PDAs.
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OA16.03 - The ALCF Centers of Excellence Model Delivers a Standard of Care to the Community Similar to Academic and Research Centers (Abstract under Embargo until December 4, 7:00 CET) (ID 6334)
16:00 - 17:30 | Author(s): L. Fine, G. Walia, R.U. Osarogiagbon
- Abstract
- Presentation
Background:
The disparities in lung cancer treatment and outcomes among minorities are well documented.1 Further, 80% of cancer patients are treated in the community hospital setting yet may not receive the same level of care as those treated at leading academic centers. The Bonnie J. Addario Lung Cancer Foundation (ALCF) Centers of Excellence (COE) program addresses this unmet need. The COE program is a patient-centric model for lung cancer that establishes a standard of care for community hospitals which often treat minority and underserved patient populations. The COE program, which currently includes 13 hospitals in regions of high unmet need, aims to improve the standard of care, patient experience and patient outcome by offering patients and caregivers the same type of multi-disciplinary and comprehensive care provided at leading academic centers. ALCF also provides lung cancer education and services to patients, caregivers and the community.
Methods:
The COE program tracks patient process data longitudinally for multiple quality-of-care metrics, including disease stage at diagnosis; molecular testing; tumor board review; time from diagnosis to treatment; treatment type; and clinical trial participation. Site data will also be monitored to provide a contextual picture of the program including total patients seen, demographics, insurance mix, rates and outcomes of molecular testing among other metrics. Data is analyzed across the COE community and against comparator groups to demonstrate impact of the COE program.
Results:
The COE program serves thousands of patients each year with a significant representation of minorities and underserved populations. Baptist Memorial Health Care System is an example of a COE that has demonstrated implementation of the COE model by providing multi-disciplinary care to a diverse population. Among those reporting race at Baptist, minorities represent more than 30% of lung cancer patients. Memorial Health Care System is another COE that is reaching and serving a diverse patient population. The patient mix at Memorial is : 64% whites; 18% Hispanics; and 18% African American. At Memorial, approximately 10% of the patient population is uninsured. Further, Memorial molecularly tests all stage III/IV patients. Compared with community hospitals in the National Cancer Database the patient mix is about 84% white, 2.5% Hispanic and 11% African American with 3% uninsured.
Conclusion:
The ALCF COE program is demonstrating that underserved lung cancer patient populations can be reached and receive standard of care treatment. The patient-focused COE approach effectively removes barriers to quality care.
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OA16.04 - Discussant for OA16.01, OA16.02, OA16.03 (ID 6963)
16:00 - 17:30 | Author(s): J. Schiller
- Abstract
- Presentation
Abstract not provided
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OA16.05 - Socioeconomic Determinants of Late Diagnosis of Lung Cancer in France: A Nationwide Study (the TERRITOIRE Study) (ID 4840)
16:00 - 17:30 | Author(s): P.J. Souquet, I. Durand-Zaleski, C. Chouaid, D. Debieuvre, A. Scherpereel, J. Fernandes, V. Westeel, C. Blein, A. Gaudin, S. Leblanc, H. Lemasson, N. Ozan, F. Cotté, P. Chauvin
- Abstract
- Presentation
Background:
Socioeconomic disparities in survival of patients with lung cancer have been identified in many countries. The aim of this study was to examine determinants of late diagnosis of lung cancer in France.
Methods:
All patients with a first diagnosis of lung cancer in 2011 in the National hospitals databases were included. Information on gender, age, presence of metastasis at diagnosis and any significant chronic comorbidities (hypertension, diabetes mellitus, renal insufficiency, and other chronic lung diseases) was retrieved. Based on municipality of residence, patients were classified by population density, social deprivation, access to general practitioners and pulmonologists.
Results:
We identified 41,015 patients newly diagnosed for lung cancer in French hospitals. Mean age at diagnosis was 66.4 (±11.9) years and 72% patients were men. 53% (N=21,613) patients were metastatic at the time of diagnosis. This rate was higher for patients in public compared to private hospitals (56.1% vs 42.9%, p<0.0001) and in community compared to university hospitals (60.2% vs 49.6%, p<0.0001). Multivariate analysis found that metastases at the time of diagnosis were significantly associated with a younger age (55 years or less, OR: 1.22 [95%CI:1.16–1.29]; p<0.0001), a low access to pulmonologists (OR: 1.13 [95%CI:1.04–1.23]; p=0.004), a rural or semi-rural dwelling (OR: 1.07 [95%CI:1.02–1.13]; p=0.004) and deprived areas (OR: 1.06 [95%CI:1.01–1.11]; p=0.01). Of the 8,413 patients (20%) who were initially admitted through emergency room (ER) 68.1% had metastatic tumors. Multivariate analysis showed significantly higher rate of admission through ER at diagnosis in patients from most deprived areas (OR: 1.44 [95%CI:1.37–1.52]; p0.0001), rural or semi-rural (OR: 1.25 [95%CI:1.19–1.32]; p<0.0001), with a low access to pulmonologists and general practitioners (OR: 1.24 [95%CI:1.17–1.30]; p<0.0001 and 1.15 [95%CI:1.08–1.23]; p<0.0001, respectively). Gender (male) and presence of comorbidities were also significant determinants of metastatic disease and admission through ER at diagnosis.
Conclusion:
A majority of French patients with lung cancer were initially metastatic at the time of diagnosis and 1 out of 5 were diagnosed following admission through ER. Residential socioeconomic indicators and access to general practitioners and pulmonologists were significantly associated with these indicators of poor outcome.
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OA16.06 - Willingness for Multiple Biopsies to Improve Quality of Lung Cancer Care: Understanding the Patient Perspective (ID 6052)
16:00 - 17:30 | Author(s): U. Basu Roy, S. Mantel, M. Jacobson, A. Ferris
- Abstract
- Presentation
Background:
In this era of precision medicine, biomarker testing of cancer tissue is sometimes necessary to match the right patient to the right treatment. A patient might need multiple biopsies if there is recurrence of lung cancer, or to determine eligibility for a new drug or participation in a clinical trial. Anecdotal evidence suggests that physicians are unwilling to recommend additional biopsies because they assume that the patients are likely to refuse.
Methods:
To understand this patient-physician communications gap, we asked 340 lung cancer survivors through an online survey about their willingness to undergo additional biopsies. The survey was fielded through various social media platforms as well as through an independent research panel.
Results:
Three-quarters of the survivors surveyed indicated their willingness to have an additional biopsy, regardless of whether they reported any pain or complications from their initial biopsy. Specifically, among the survivors who were willing to undergo an additional biopsy: Almost all of the survivors (82%) would do so if it would help their health care team better match treatment to their specific cancer and personalize their care, versus just being told the test was to look for mutations. In other words, understanding the end benefit of having the test is an important piece of communication. Although almost 50% reported pain or complications from their initial biopsy, this group indicated equal willingness to have another biopsy as those without any issues. If the doctor were to recommend an additional biopsy or a biopsy after the start of treatment, nearly half would definitely undergo one. About two-thirds of the survivors felt that their doctor explained the reason for getting their initial biopsy really well.
Conclusion:
The study reinforces the importance of a patient-centric model in medicine–in which meaningful and timely information is provided to patients to enable them to be partners in their own care. The study has the following implications for different stakeholders: Patients: To ask their doctor about new treatments and discuss the need for additional biopsies if necessary. Understanding the end benefit of having the test is an important piece of communication. Patient Advocacy Organizations: To educate patients and physicians about having an open dialogue to help patients become equal partners in their treatment decision-making. Physicians: To discuss the benefits and the risks of an additional biopsy with their patients and how it may help decide course of treatment.
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OA16.07 - Patient-Driven Epidemiologic Assessment of ROS1-Fusion Driven Cancers (ID 6239)
16:00 - 17:30 | Author(s): G. Walia, R. Patients, B.J. Addario, M.I. Patel, D. LeDuc
- Abstract
- Presentation
Background:
There are limited data on factors that contribute to the development of ROS1-fusion positive cancers. A group of ROS1+ patients approached the Bonnie J. Addario Lung Cancer Foundation (ALCF) for support of ROS1 research. As a first step in this unique, patient-driven effort, we designed a survey to understand epidemiologic/clinical factors that may contribute to the development and progression of ROS1 cancers. We aim to collect data with biospecimens and make these available through an open-access data-sharing platform to accelerate ROS1 research.
Methods:
With guidance from ROS1 patients, we designed a 204-question survey, obtained Stanford University IRB approval. The survey on the ALCF website from May 18, 2016, was widely publicized through conferences, patient support networks, social media and community-based outreach. The survey questions address demographic-, clinical-, diagnostic and treatment- factors, family and reproductive history, dietary, exercise, environmental exposure and hormone and substance use. We used Z-proportions test for statistical significance defined as p<0.05.
Results:
In 53 days, 95 global patients with ROS1-fusion+ cancer responded to the survey (median age at diagnosis 56 years). Respondents were 71% female (n=52/73), 79% never smokers (49/62). 71% respondents were otherwise healthy before diagnosis (n=46/65). The majority of respondents were diagnosed with lung cancer (n=68/72); and one each with gastric, ovarian, cervical and liver cancer. 76% reported metastatic disease (n=52/68) at diagnosis with the most common site of metastases as contralateral lung (65%) and bone (46%). 52% patients reported their ROS1 cancers were not detected at diagnosis (n=35/67); 80% didnot know their specific translocation (51/64). 71% patients received molecular testing on physicians’ orders (n=45/63), with 21% self-initiating molecular testing. Despite the availability of targeted treatments and clinical trials, most patients were prescribed chemotherapy in their first (62%), second (49%), third (60%) and further lines of therapy. 76% patients reported that crizotinib was the therapy that worked best, with 96% reporting significant improvement in symptoms and QoL. We found no significant correlations between oral contraceptive/hormone/anabolic steroid use, occupational exposure, geographic area of employment/residence, family history of cancer, and incidence of ROS1+ cancer.
Conclusion:
This is a unique patient and non-profit advocacy group-driven investigation that seeks to understand factors that may influence development and treatment of ROS1 cancers. The results highlight patient-centricity, the importance of upfront molecular testing and targeted therapies. We report patient-reported experiences with ROS1 testing and durable responses to targeted treatments e.g. crizotinib. As the study is ongoing, we will update results in December 2016.
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OA16.08 - Discussant for OA16.05, OA16.06, OA16.07 (ID 6978)
16:00 - 17:30 | Author(s): P. Berzinec
- Abstract
- Presentation
Abstract not provided
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Author of
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ISS10 - Industry Supported Symposium: Novel Treatment Strategies for ALK+ NSCLC: From Evidence to Practice – Novartis Oncology (ID 443)
- Event: WCLC 2016
- Type: Industry Supported Symposium
- Track:
- Presentations: 2
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ISS10.04 - The Future of ALK+ NSCLC Treatment and What this Implies for Your Clinical Practice (ID 6995)
12:45 - 14:15 | Author(s): D. Tan
- Abstract
Abstract not provided
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ISS10.05 - Panel Discussion: Challenges in Sequencing Therapy for Your ALK+ NSCLC Patients (ID 6996)
12:45 - 14:15 | Author(s): D. Tan
- Abstract
Abstract not provided
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-015 - Ceritinib as First-Line Therapy in Patients with ALK-Rearranged Non-Small Cell Lung Cancer: ASCEND-1 Subgroup Analysis (ID 5686)
14:30 - 15:45 | Author(s): D. Tan
- Abstract
Background:
In the open-label, phase 1 ASCEND-1 study (NCT01283516), ceritinib demonstrated durable whole body and intracranial responses in patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) (Kim et al. Lancet Oncol 2016). Median progression-free survival (PFS) was promising in ALK inhibitor (ALKi)-naïve patients (18.4 months), most of whom had received one or more lines of chemotherapy. Here, efficacy and safety of ceritinib are summarized in a subset of treatment-naïve patients enrolled in ASCEND-1.
Methods:
Patients with ALK+ NSCLC enrolled worldwide received ceritinib 750 mg/day (fasted). Efficacy and safety were evaluated in a subset of patients who had not received any prior systemic antineoplastic therapy. Data cut-off was 16 November 2015.
Results:
Overall, 246 patients with ALK+ NSCLC (83 ALKi-naïve and 163 ALKi-pretreated) received ≥1 dose of ceritinib, of whom 16 had not received any prior systemic antineoplastic therapy. Among the 16 treatment-naïve patients, three (18.8%) had baseline brain metastases, five (31.3%) an ECOG performance status of 0, and all had stage IV disease. Median time from primary site diagnosis to ceritinib initiation (range) was 1.8 months (1.0–35.9). At data cut-off, median duration of exposure (range) was 18.5 months (0.9–35.7) and median duration of follow-up (range) was 29.6 months (4.7–39.1). In these 16 treatment-naïve patients, per investigator assessment, the overall response rate was 68.8% (95% confidence interval [CI]: 41.3, 89.0) and the disease control rate was 87.5% (95% CI: 61.7, 98.4). Median duration of response was 21.1 months (95% CI: 5.5, 31.1). Median investigator-assessed PFS was 19.3 months (95% CI: 4.2, 26.3), and median overall survival was 39.1 months (95% CI: 19.1, 39.1). Among three patients with baseline brain metastases, one had brain metastases selected as target lesion and achieved a partial intracranial response. The most frequently reported any-grade adverse events (AEs), regardless of study drug relationship, were diarrhea (93.8%), nausea (81.3%), ALT or AST increase (each 81.3%), and vomiting (62.5%). AEs requiring intervention were predominantly managed with dose reduction/interruption. Overall, 13 patients (81.3%) discontinued treatment, due to disease progression (n=6), consent withdrawal (n=3), AEs (n=2), administrative problems or death (each n=1).
Conclusion:
Ceritinib demonstrated durable efficacy in treatment-naïve patients with ALK+ NSCLC. Safety was consistent with the overall ASCEND-1 study population. An ongoing, prospective, phase 3 study (ASCEND-4) in which patients are randomized to receive either ceritinib or chemotherapy will provide further evidence for the clinical benefit of ceritinib in previously untreated patients with ALK+ NSCLC.
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P3.02a-025 - PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4) (ID 5128)
14:30 - 15:45 | Author(s): D. Tan
- Abstract
Background:
Here, we present the patient-reported outcomes (PROs) of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated, ALK+, advanced, nonsquamous NSCLC patients (N=376) were randomized (1:1) to ceritinib 750 mg/day (n=189) or chemotherapy (n=187; [pemetrexed 500 mg/m[2 ]plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed). PROs were assessed using EORTC quality-of-life questionnaire (QLQ-C30), the lung cancer module (QLQ-LC13), Lung Cancer Symptom Scale (LCSS), and EQ-5D.
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. PRO compliance was high, ≥80% at most timepoints. Ceritinib significantly prolonged time to deterioration of lung cancer-specific symptoms (pain, dyspnea, and cough) versus chemotherapy in both LCSS and QLQ-LC13 instruments (composite endpoints for LCSS, HR=0.61 [0.41, 0.90]; and QLQ-LC13, HR=0.48 [0.34, 0.69]). Time to deterioration in LC13 questionnaire was significantly longer with ceritinib versus chemotherapy (23.6 [20.7, NE] vs 12.6 [8.9, 14.9] months) (Table). In the QLQ-C30 instrument, 4 of 5 functional domains and 6 of 9 symptom scales improved with ceritinib (P< 0.05); 2 scales related to gastrointestinal symptoms indicated deterioration for ceritinib. In agreement with most other scales showing symptom improvement, ceritinib demonstrated significant improvements in Global Health Status/QoL in the same instrument (QLQ-C30, P<0.001) as well as for EQ-5D-5L index (P<0.001) and EQ-5D-5L VAS (P<0.05 from cycle 13 until 49). Figure 1
Conclusion:
Untreated ALK+ NSCLC patients experienced significantly greater improvements in lung cancer-specific symptoms on treatment with ceritinib. General health status was significantly improved with ceritinib versus chemotherapy. Overall, PRO results from all 4 instruments independently showed improvements highlighting the consistency and robustness of these findings.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-117 - Phase Ib Results from a Study of Capmatinib (INC280) + EGF816 in Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 5012)
14:30 - 15:45 | Author(s): D. Tan
- Abstract
Background:
Among patients with EGFR-mutant NSCLC who progress on EGFR tyrosine kinase inhibitors (EGFR-TKIs), the most common (50%) resistance mechanism is secondary T790M mutation. cMET dysregulation is the second most common mechanism, with amplification occurring in 5‒22% of resistant patients. This study evaluates targeting these two mechanisms to overcome acquired resistance to EGFR-TKIs. Capmatinib (INC280) is a highly selective, potent cMET inhibitor with clinical activity in patients with cMET dysregulation. EGF816 is an irreversible EGFR-TKI that selectively inhibits T790M and EGFR-activating mutations, with antitumor activity in EGFR[T790M]-mutated NSCLC. In this open-label Phase Ib/II study, capmatinib was combined with EGF816 in patients with EGFR-mutated, EGFR-TKI resistant NSCLC.
Methods:
The Phase Ib primary objective is estimation of the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of the combination using an adaptive Bayesian logistic regression model. Eligible patients (≥18 years; ECOG PS ≤2) must have documented EGFR-mutated (exon19del and/or L858R) NSCLC and documented progression (RECIST v1.1) while on EGFR-TKI treatment. Patients received capmatinib (starting dose 200 mg BID) plus EGF816 (starting dose 50 mg QD).
Results:
At the data cut-off (Aug 1, 2016), 33 patients were enrolled at five capmatinib BID/EGF816 QD mg dose levels (200/50 [n=4]; 200/100 [n=5]; 400/75 [n=3]; 400/100 [n=16]; 400/150 mg [n=5]); 18/33 (55%) patients discontinued treatment, mainly (13 [39%] patients) due to disease progression. Dose-limiting toxicities (DLTs) occurred in 4 patients: in 1 patient at the 200/50 dose level (increased alanine aminotransferase), 1 patient at the 400/100 dose level (anaphylactic reaction), and 2 patients at the 400/150 dose level (pyrexia, maculopapular rash, and allergic dermatitis). The most frequent (≥30%) any-grade adverse events (AEs), regardless of causality, were nausea (55%), peripheral edema (45%), increased amylase (42%), increased blood creatinine (36%), decreased appetite and diarrhea (both 30%). The most frequent (>10%) Grade ≥3 AEs were maculopapular rash (18% [mainly in the 400/150 cohort]) and increased amylase (12%). Capmatinib and EGF816 exposure increased with dose; preliminary data indicate a ~35% increase in EGF816 exposure (AUC) at steady state when co-administered with the capmatinib RP2D, compared with single-agent exposure. The investigator-assessed overall response rate was 42% (2/33 complete responses; 12/33 partial responses) across all dose levels and 50% (8/16 patients) at the 400/100 dose level, regardless of molecular status of resistance.
Conclusion:
The RP2D of the combination was declared as capmatinib 400 mg BID + EGF816 100 mg QD. Preliminary antitumor activity was observed across dose levels, independent of T790M status.
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PL03 - Presidential Symposium (ID 428)
- Event: WCLC 2016
- Type: Plenary
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, R. Pirker
- Coordinates: 12/06/2016, 08:35 - 10:25, Hall D (Plenary Hall)
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PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) (Abstract under Embargo until December 6, 7:00 CET) (ID 4987)
08:35 - 10:25 | Author(s): D. Tan
- Abstract
- Presentation
Background:
Here, we report results of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated ALK+ (IHC confirmed), advanced, nonsquamous NSCLC patients (N=376; median age, 54 years) were randomized (1:1) to ceritinib 750 mg/day (n=189 [59 with brain metastases (BM)]) or chemotherapy (n=187 [62 with BM]; [pemetrexed 500 mg/m[2] plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed), stratified by WHO PS (0 vs 1-2), BM at screening, and prior neo-/adjuvant chemotherapy. Crossover from chemotherapy to ceritinib was allowed at progression (n=80 crossed-over).
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. Median follow-up duration was 19.7 months (randomization to cut-off date). The study met its primary objective, with ceritinib demonstrating statistically significant improvement in BIRC PFS (RECIST 1.1; median, 16.6 [12.6, 27.2] vs 8.1 months [5.8, 11.1], HR=0.55, P<0.001) versus chemotherapy. OS was immature (HR, 0.73 [0.50, 1.08]; P=0.056) with 42.3% of required events at interim analysis. ORR (BIRC, 72.5% vs 26.7%) and DOR (BIRC, median, 23.9 vs 11.1 months) were also higher with ceritinib versus chemotherapy. Among patients with measurable baseline BM and ≥1 postbaseline assessment, intracranial ORR (BIRC neuroradiologist; modified RECIST v1.1) was higher with ceritinib (72.7% [49.8, 89.3] vs 27.3% [10.7, 50.2]) versus chemotherapy (Table). Most common AEs (>50%) with ceritinib were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), ALT increase (60.3%), and AST increase (52.9%). Overall, 5.3% ceritinib- and 11.4% chemotherapy-treated patients discontinued due to AEs suspected to be drug-related. Figure 1
Conclusion:
First-line ceritinib achieved statistically significant and clinically meaningful improvement in median PFS with an estimated 45% risk reduction in advanced ALK+ NSCLC versus chemotherapy including maintenance. Moreover, ceritinib achieved high and durable systemic responses and high OIRR in patients with measurable BM. Safety profile of ceritinib is consistent with previously reported.
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SC28 - Novel Clinical Trial Designs (ID 352)
- Event: WCLC 2016
- Type: Science Session
- Track: Trial Design/Statistics
- Presentations: 1
- Moderators:S. Michiels, L.R. Pilz
- Coordinates: 12/07/2016, 11:00 - 12:30, Lehar 1-2
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SC28.02 - Umbrella and Basket Designs (ID 6718)
11:00 - 12:30 | Author(s): D. Tan
- Abstract
- Presentation
Abstract not provided
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