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Benjamin Solomon



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    ES19 - Patient-Reported Outcomes, Patient Registries and Real-World Evidence: Learning Directly from Patients (ID 224)

    • Event: WCLC 2020
    • Type: Educational Session
    • Track: Patient Advocacy
    • Presentations: 1
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      ES19.03 - Understanding the Feasibility of Patient Reported Outcomes (ID 4058)

      16:45 - 17:45  |  Author(s): Benjamin Solomon

      • Abstract

      Abstract

      Background

      There is increasing pressure to gather patient-reported outcomes (PROs) to support activities like the day-to-day care of individual patients and value-based healthcare initiatives. A PRO refers to “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else” [1]. PRO measures (PROMs) are typically used to capture PRO data but most were developed for research rather than clinical uses [2]. Consequently, most validity evidence supports group- rather than individual-level uses.

      While one recent trial demonstrated benefits associated with symptom monitoring in advanced cancer patients, evidence from a well-conducted systematic review was less positive [3]. Statistically significant findings were few, most effect sizes were small-to-moderate and evidence on patient safety and costs are almost entirely lacking. So too are feasibility tests and large-scale implementation studies with lung cancer patients in ‘real world’ settings.

      Our study aimed to:

      1. Develop a PRO framework to guide routine PRO collection and use with lung cancer patients

      2. Assess both the feasibility of implementing the PRO framework in a ‘real world’ setting and its clinical utility

      This presentation will report on the second aim only.

      Development of the PRO framework, including its purpose, minimum PRO dataset, and data collection and quality assurance methods, has been presented elsewhere [4]. A multi-disciplinary team of experts and consumers were involved in its development and the minimum dataset comprises the ICHOM patient-reported health status measures (the EORTC QLQ-C30 and –LC13), the PROMIS Social Isolation v2.0-short form and weight loss; comorbidities, smoking status and performance status are already collected by the lung cancer service as part of their Thoracic Malignancies Cohort (TMC).

      Methods

      Study design. Mixed-methods feasibility study.

      Setting. A large Australian cancer centre.

      Participants. Eligible patients were ≥18 years, diagnosed with lung cancer, English-speaking, consented to the TMC, scheduled to receive chemo-radiation. Eligible staff were clinicians who provided care to eligible patients.

      Recruitment, assessment and feedback. A researcher approached potentially eligible patients in person or by phone. Consenters completed baseline assessments with the researcher, then chose their preferred method for follow-up (pen-and-paper or electronic at 2, 6 and 12 months post-baseline). Email alerts were sent to the lung nurse specialist when patients reported a score of 3/4 (quite a bit/very much) on any EORTC item. Actions taken were left to the discretion of the nurse specialist.

      Variables and data sources. Data used to describe the sample were gathered from the TMC database. Operational, patient self-report and interview data were used to evaluate the feasibility of implementing the PRO framework and the clinical utility of the PRO data. Proctor et al.’s taxonomy of implementation outcomes [5] was used as an organising framework for evaluation data and data gathered pre-implementation relevant to acceptability and adoption. The taxonomy helped ensure clarity of definitions, and specification of levels of analysis and measures for each outcome of interest (Figure 1).

      Quantitative and qualitative methods. Quantitative data was analysed descriptively in R. Interviews were audio-recorded, transcribed verbatim and analysed using a thematic, descriptive approach.

      Results

      Adoption. 28 of 32 eligible patients consented to participate (88%).

      Median age was 64 years (interquartile range: 58-71 years). Most participants were female (18/28) and had late stage (III/IV) disease (26/28).

      Acceptability. PROMs questions were seen as comprehensible, applicable, clear and not burdensome by around 90% of patients.

      Appropriateness and feasibility. Staff and patient views on whether the PRO framework was fit for purpose and useful were mixed. There was agreement that using PROs is a ‘good idea’ but members of both groups questioned the relevance, functionality and suitability of the framework. The actual impact on care/decision-making was debated, as was the timing of assessments and the measures. Obvious concerns included scalability and modification to accommodate non-English-speaking patients.

      Fidelity. We were not able to create a seamless link between our study database and the TMC database. However, retention secondary to death was high at all assessments (≥87%). Participation and adherence, secondary to availability, were high at baseline (≥93%) but substantially lower at follow-up assessments (74-78% and 61-67%, respectively).

      Discussion

      With dedicated staff to support data collection and curation, routine collection of PROMs—like those recommended by ICHOM—was, at face value, acceptable in English-speaking patients. Adoption was high. Perceived and actual fit and utility, on the other hand, was called into question by both staff and patients. Fidelity was mixed.

      Conclusion. PROMs earmarked for value-based care initiatives and other group-level uses have questionable utility—relevance, functionality and suitability—for monitoring individual cancer patients. This issue is well-documented in the literature [2] but often ignored.

      iaslc 2021 gough figure 1.png

      References

      [1] US Food and Drug Administration. Guidance for industry patient-reported outcome measures: use in medical product development to support labeling claims, 2009.

      [2] Porter I, et al. Framework and guidance for implementing patient-reported outcomes in clinical practice: evidence, challenges and opportunities. J Comp Eff Res. 2016;5:507-19.

      [3] Kotronoulas G, et al. What is the value of the routine use of patient-reported outcome measures toward improvement of patient outcomes, processes of care, and health service outcomes in cancer care? A systematic review of controlled trials. J Clin Oncol. 2014;32:1480-501.

      [4] Moloczij N, et al. Development of a hospital-based patient-reported outcome framework for lung cancer patients: a study protocol. Health Qual Life Outcomes. 2018;16:10.

      [5] Proctor E, et al. Outcomes for implementation research: conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment Health. 2011;38:65-76.

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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.05 - LIBRETTO-431: Selpercatinib in Treatment-Naïve Patients with RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC). (ID 807)

      00:00 - 00:00  |  Author(s): Benjamin Solomon

      • Abstract

      Introduction

      Selpercatinib (LOXO-292) is a highly selective and potent inhibitor of RET signaling. In the LIBRETTO-001 Phase I/II trial, selpercatinib treatment resulted in a 64% objective response rate (ORR) (95% confidence interval [CI]: 54-73%) in the registration dataset (n=105) of patients with RET+ NSCLC who previously received platinum-based chemotherapy and an 85% ORR (95% CI: 70-94%) in treatment-naïve patients with RET+ NSCLC (n=39). Although the duration of response (DOR) and progression free-survival (PFS) were not yet mature in treatment-naïve patients, in patients who previously received chemotherapy, the median DOR was 18 months (95% CI: 12-not estimable [NE]), median PFS was 17.5 months (95% CI: 12-NE), and CNS ORR per RECIST 1.1 was 91% (95% CI: 59-100%) (n=10/11). The most common adverse reactions included dry mouth (39%), diarrhea (37%), hypertension (35%), and fatigue (35%). The majority of adverse reactions were Grade 1 or Grade 2. The most common lab abnormality was increased alanine aminotransferase (ALT) (51%)/aspartate transaminase (AST) (45%). A total of 5% of patients discontinued due to an adverse reaction.

      The LIBRETTO-431 trial, is a global, open-label, randomized, controlled, Phase 3 trial evaluating selpercatinib vs platinum-based and pemetrexed treatment +/- pembrolizumab in treatment-naïve patients with locally advanced or metastatic RET+ non-squamous NSCLC (NCT04194944).

      Methods

      Patients will be randomized to receive selpercatinib 160 mg BID in 3-week cycles (Arm A) or pemetrexed (500 mg/m2 IV) in 3-week cycles plus investigator’s choice of carboplatin (AUC 5) or cisplatin (75 mg/m2 IV) for 4 cycles (Arm B). For patients in Arm B, at the investigator’s discretion, pembrolizumab (200 mg IV) may also be given for up to 35 cycles and patients may receive maintenance pemetrexed +/- pembrolizumab. Crossover to selpercatinib is allowed for Arm B patients who have disease progression. Treatment will be discontinued for progressive disease, unacceptable toxicity, decision to withdraw or death. Stratification factors include geography: East Asian versus non-East Asian, brain metastases: presence versus absence, and intended treatment if randomized to Arm B: +/- pembrolizumab. RET status may be determined in tumor (by PCR or NGS) or in blood (by NGS) using a qualified local test or a Lilly-enabled regional test. Key eligibility criteria include age ≥18 years; treatment-naïve; non-squamous Stage IIIB-IIIC not suitable for surgery/radiation therapy or Stage IV NSCLC; measurable disease by RECIST 1.1; ECOG performance status 0-2. Key exclusion criteria include presence of other known oncogenic drivers and symptomatic central nervous system metastases. Tumor assessments will be performed until progressive disease, the start of a new anticancer treatment, death or study completion. The co-primary endpoint, PFS by independent review in intent-to-treat (ITT) patients with pembrolizumab (if assigned to control), will act as a gatekeeper to the co-primary endpoint PFS by independent review in the ITT population. Secondary endpoints include investigator assessed PFS, ORR/DOR, intracranial ORR/DOR, overall survival, time to deterioration in pulmonary symptoms, progression after the next line of therapy, RET fusion status: local versus central, and safety/tolerability. The study was initiated in March 2020 and enrollment is ongoing.

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    IS07 - Industry Symposium Sponsored by Roche: Expert Perspectives on the Management of Lung Cancer (ID 284)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS07.01 - The Past, Present and Future of Biomarker-Driven Advanced NSCLC (ID 4339)

      16:45 - 17:45  |  Presenting Author(s): Benjamin Solomon

      • Abstract

      Abstract not provided

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    MA11 - Expanding Targetable Genetic Alterations in NSCLC (ID 251)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
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      MA11.07 - Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors (ID 3255)

      14:15 - 15:15  |  Author(s): Benjamin Solomon

      • Abstract

      Introduction

      Repotrectinib is a next-generation ROS1/TRK TKI with >90-fold greater potency than crizotinib and entrectinib against ROS1 and >100-fold greater potency than larotrectinib against TRK in engineered Ba/F3 cell proliferation assays. In the Phase 1 portion of TRIDENT-1 study, repotrectinib demonstrated encouraging overall clinical activity in patients (pts) with ROS1 fusion+ NSCLC and TRK fusion+ solid tumors, especially in those pts with ROS1+ NSCLC who are TKI naive.

      Methods

      In Phase 1 portion of the study, the Recommended Phase 2 Dose (RP2D) for repotrectinib was determined to be 160 mg QD for 14 days followed by 160 mg BID if tolerated. Currently, this global trial (Clinical trial information: NCT03093116) is actively enrolling pts whose cancers harbor a ROS1 or NTRK1/2/3 fusion in six phase 2 expansion cohorts (see table). The primary endpoint for the Phase 2 portion is confirmed overall response rate (cORR) by Blinded Independent Central Review (BICR) using RECIST v1.1. An early interim analysis on 39 pts enrolled in Phase 2 was conducted using investigator assessment.

      Results

      Phase 1: Utilizing a 22 July 2019 data cutoff, cORR was 91% by BICR in 11 ROS1 TKI-naïve pts with 5 responses ongoing. The median duration of response (DOR) for the 10 confirmed responders was 23.1 months (95% CI: 5.6–not reached [NR]) and median progression-free survival (PFS) was 24.6 months (95% CI: 7.2 – NR). As of 6 April 2020, with an additional 8.5 months of follow-up, 4 of the 5 previously responding TKI-naïve pts remained in a partial response (PR) per physician assessment data and 7 TKI-naïve pts remained on treatment, range (17.3+ - 34.2+ months).

      Phase 2: The early Phase 2 TRIDENT-1 dataset utilizing a July 10, 2020 data cutoff includes the first 39 treated pts across six cohorts who have had at least one post-baseline scan. Data are summarized in table below:

      TRIDENT-1 Study of Repotrectinib

      (Phase 2 Cohorts)

      ORR

      95% CI

      ROS1+ TKI-Naïve, up to 1 line of chemotherapy or immunotherapy

      (EXP-1)

      86%*

      (6/7)

      (42-100)

      ROS1+ TKI-Pretreated, 1 prior TKI, with prior platinum-based chemotherapy

      (EXP-2)

      40%

      (2/5)

      (5-85)

      ROS1+ TKI-Pretreated, 1 prior TKI, without prior platinum-based chemotherapy

      (EXP-4)

      67%

      (4/6)

      (22-96)

      ROS1+ TKI-Pretreated 2-prior TKIs, without prior platinum-based chemotherapy

      (EXP-Other)

      40%

      (2/5)

      (5-85)

      NTRK TKI-Pretreated

      (EXP-6)

      50%

      (3/6)

      (12-88)

      * Since the data cutoff the 7th ROS1 TKI-naïve patient achieved an unconfirmed PR.

      Repotrectenib was well tolerated, with predominantly grades 1/2 adverse events. TEAEs in > 25 % of pts were dizziness (62%), fatigue (39%), constipation (33%), dysgeusia (33%), and dyspnea (28%). 90% of 39 treated pts in Phase 2 escalated to 160 mg twice daily (BID) after 14 days per the study defined dose titration approach. There were no Grade 4 or Grade 5 TRAEs.

      Conclusion

      Repotrectinib was well tolerated and continues to demonstrate encouraging overall clinical activity in pts with ROS1 fusion-positive NSCLC and TRK fusion-positive solid tumors.

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      MA11.08 - Patient-Reported Outcomes from the Randomized Phase 3 CROWN Study of First-Line Lorlatinib versus Crizotinib in ALK+ NSCLC (ID 3257)

      14:15 - 15:15  |  Author(s): Benjamin Solomon

      • Abstract

      The abstract for this presentation is currently under embargo or has not been submitted.

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    P39 - Patient Advocacy (ID 168)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Patient Advocacy
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P39.06 - Surviving Metastatic Non-Small Cell Lung Cancer – Experience and Supportive Care Needs of Patients Receiving Novel Therapies  (ID 1076)

      00:00 - 00:00  |  Author(s): Benjamin Solomon

      • Abstract

      Introduction

      Immunotherapy (IT) and targeted therapies (TT) have improved survival for many patients (pts) with metastatic non-small cell lung cancer (mNSCLC). However, the lived experience of this cohort of pts is under-studied. We conducted a single centre, qualitative study to understand concerns and supportive care needs of this novel survivor population.

      (Complementary data was accepted for online only abstract at ASCO 2020)

      Methods

      Eligible pts had mNSCLC, were aged >18, English speaking and were >6 months post initiation of IT/TT without progressive disease. Semi-structured interviews were conducted focusing on physical, psychological, social and functional impacts of diagnosis, therapy and prognosis. Interviews were audio-recorded and transcribed. The framework method of analysis was used.

      Results

      20 pts were interviewed between May-December 2019; median age 62 years (range 34-83), 13 (65%) female; median time since diagnosis of mNSCLC 27 months (range 10-108). 12/20 (60%) had tumours with a targetable molecular alteration (EGFR/ALK/BRAF); 6 were receiving IT, 11 TT, 2 IT and chemotherapy, 1 IT and TT.

      Dominant themes included:

      a) experience of chronic toxicities (cutaneous, gastrointestinal, fatigue) and strategies to maintain quality of life in the setting of ongoing treatment requirements (optimisation of supportive care medications, dosing alterations, practical measures such as sun avoidance)

      b) psychological concerns (living with uncertainty regarding prognosis, fear of cancer progression [FCP], scan-related anxiety, stigma around smoking, sense of loneliness in disease experience, loss of future opportunities) and coping strategies (social and formal supports)

      c) desire for assistance with practical issues (financial planning, returning to work, challenges of long-term participation in clinical trials on quality of life, difficulty planning for the future).

      Desire for tailored information pertinent to newer treatment paradigms with IT and TT was also expressed by many participants in recognition that their lived patient experience (and potentially prognosis) differed from other patients with mNSCLC who were not eligible for IT or TT. This was reported across a number of domains including: internet resources, support groups specific to patients on IT and TT, challenges in accessing pertinent information regarding disease and/or treatment, and advice by non-specialist health-care providers that was not specific to this particular pt cohort. Appearing well despite having mNSCLC and hence not fulfilling a typical ‘sick role’ paradigm was noted by some pts to have other implications including lack of empathy from others or practical assistance eg from the workplace.

      Conclusion

      Longer term survivors of mNSCLC report significant physical, psychological and functional concerns and unmet needs. Self-management strategies for chronic toxicities, professional psychological services to manage FCP and scan-related anxiety, and tailored information regarding work and financial planning may mitigate these concerns. Further work should examine these issues in a larger population. It is likely future survivorship care of pts with mNSCLC will require a nuanced approach in recognition of the apparent spectrum of lived experience.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.64 - Alternating Osimertinib and Gefitinib as Second-Line Treatment for EGFR-Mutated NSCLC Harbouring a T790M Resistance Mutation (OSCILLATE) (ID 3282)

      00:00 - 00:00  |  Presenting Author(s): Benjamin Solomon

      • Abstract

      Introduction

      Osimertinib is standard of care for advanced EGFR-mutated NSCLC following the emergence of T790M resistance mutations, with a median progression-free survival (PFS) of 10 months. Mechanisms of resistance to osimertinib include acquisition of C797S mutations and loss of T790M mutations. We hypothesised that alternating treatment with osimertinib and gefitinib would modulate clonal populations within tumors and delay the emergence of resistance. The aim of this study was to assess the activity, feasibility, and safety of alternating therapy, and to explore plasma ctDNA dynamics and mechanisms of resistance.

      Methods

      This open label, single-arm, multi-centre, investigator-initiated, phase 2, cooperative group trial included adults with metastatic, EGFR-mutated NSCLC with an acquired, T790M resistance mutation demonstrated in tissue or plasma. Study treatment was osimertinib 80mg daily for 8 weeks, then alternating 4-week cycles of gefitinib 250mg daily and osimertinib 80mg daily, until disease progression. Blood samples for ctDNA were taken on day 1 of each 28-day cycle, and day 15 of cycles 3 and 4. The primary endpoint was PFS at 1 year. Secondary endpoints included feasibility of alternating treatment, time to treatment failure (TTTF), objective tumour response (OTR), overall survival (OS), and adverse events (AE).

      Results

      We recruited 47 eligible participants from September 2017 to June 2019: 63% female, 55% aged 60 or older; 96% ECOG 0-1; 67% had an exon 19 deletion, 31% had an exon 21 L858R substitution, 4% had an uncommon or compound EFGR mutations; and, 23% had brain/leptomeningeal metastasis. PFS at 1 year was 38% (27% to 55%), median PFS was 9.2 months (7.2 to 13), and median TTTF was 9.4 months (7.6 to 13). The OTRR was 40% (19/47, 95% CI 28 to 55%). Alternating treatment was feasible with only 1 participant discontinuing gefitinib due to treatment side-effects, and only 2 requiring a treatment interruptions within the first 6 months, both for SAEs unrelated to treatment. The most frequent grade 3-4 AE were headache and nausea, each occurring in 2 participants. The one death that occurred during study treatment was due to lung infection and judged unrelated to treatment.

      Conclusion

      Alternating osimertinib and gefitinib was safe, feasible, and PFS was similar to that of single-agent osimertinib, as second-line treatment for EGFR-mutated NSCLC with a T790M resistance mutation. Analyses of ctDNA levels, dynamics, and mechanisms of resistance are ongoing.

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    P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P84.09 - Asian Subgroup Analysis of a Phase II Study Evaluating Lorlatinib Efficacy in Previously Treated ALK-Positive Advanced NSCLC (ID 3566)

      00:00 - 00:00  |  Author(s): Benjamin Solomon

      • Abstract

      Introduction

      Lorlatinib is a selective, potent, brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) that targets ALK and ROS1. In a global Phase II trial, lorlatinib showed substantial overall and intracranial activity in patients with ALK- or ROS1-positive advanced non-small cell lung cancer (NSCLC). Here we report the efficacy and biomarkers of lorlatinib from the Asian subgroup analysis of this trial.

      Methods

      In this ongoing, open-label, Phase II trial (NCT01970865), eligible patients with ALK- or ROS1-positive advanced NSCLC, with or without central nervous system (CNS) metastases were enrolled into six different expansion cohorts based on their ALK and ROS1 status and previous therapy, and received lorlatinib 100 mg once daily. The primary study endpoint was objective tumor response and intracranial (IC) tumor response. Efficacy analyses were conducted for Asian patients (based on race) with ALK-positive NSCLC, who received at least one previous ALK tyrosine kinase inhibitor (this is the first presentation with new data cut-off May 14, 2019). Correlation analyses with tumor tissue and cfDNA ALK resistance mutations are ongoing.

      Results

      Baseline characteristics of the 70 Asian patients (61% female, 51 years median age, 41%/54%/4% ECOG Performance Status 0/1/2, 57% brain metastases at baseline) were similar to the overall population (59% female, 53 years median age, 45%/52%/4% ECOG Performance Status 0/1/2, 67% brain metastases at baseline). Efficacy results of the total Asian population (summarized in Table 1) were similar to the overall population; with ORR of 56% versus 47%, IC-ORR of 59% versus 63% and median PFS of 8.2 versus 7.3 months, respectively.


      table 1.jpg

      Conclusion

      Lorlatinib exhibited similar efficacy in this Asian subgroup compared with the overall population.