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Benjamin J Solomon
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IBS01 - My Oligometastatic Oncogene Driven Patient (Ticketed Session) (ID 32)
- Event: WCLC 2019
- Type: Interactive Breakfast Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 07:00 - 08:00, Tokyo (1982)
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IBS01.01 - Systemic or Local Treatment: What to Do First? (Now Available) (ID 3315)
07:00 - 08:00 | Presenting Author(s): Benjamin J Solomon
- Abstract
- Presentation
Abstract
In the era of increasingly effective systemic treatments including EGFR and ALK tyrosine kinase inhibitors we will review the rationale for aggressive treatment of oligometastatic or oligopersistent disease in order to improve long term treatment outcomes. In the setting of oligometastatic disease to the brain, treatment of one or more sites of brain metastases with effective systemic treatment with stereotactic radiotherapy may allow whole brain radiation to be avoided or delayed. For extracranial disease, locally ablative therapies to solitary sites of metastases may enable potentially curative approaches to primary tumours. Further, benefit for treatment of oligo-persistent sites of disease after intial systemic treatment with local consolidative therapy has been demonstrated. Central to aggressive local approaches are appropriate staging investigations including MRI Brain and FDG-PET scan to determine the extent of metastatic disease.
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OA05 - Increasing the Impact of Nursing and Allied Health Professional Interventions in Lung Cancer Care (ID 130)
- Event: WCLC 2019
- Type: Oral Session
- Track: Nursing and Allied Professionals
- Presentations: 1
- Now Available
- Moderators:Dianne Zawisza, Maria Guerin
- Coordinates: 9/08/2019, 15:15 - 16:45, San Francisco (2009)
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OA05.01 - A Prospective Study of Swallowing and Voice Outcomes After Treatment for Small-Cell Lung Cancer (Now Available) (ID 2225)
15:15 - 16:45 | Author(s): Benjamin J Solomon
- Abstract
- Presentation
Background
Dysphagia (difficulty swallowing) and dysphonia (impaired voice) have been identified in patients with lung cancer as being a significant problem. However, research to date has been limited in its measurement and it remains unknown which patients experience dysphagia or dysphonia, and what the impact of these problems are to the patient. The purpose of this study was to identify the prevalence and nature of dysphagia and dysphonia in patients with limited stage SCLC.
Method
A prospective cohort pilot study was conducted on 12 patients receiving chemoradiotherapy for limited-stage SCLC. Data collection included: videofluoroscopy swallowing studies (VFSS) to investigate swallowing physiology, aspiration risk and oesophageal motility disorders; limitations to oral intake; patient-reported swallowing problems; and patient-reported voice problems. Data were collected before treatment and again at one, three and six months post-treatment.
Result
No patient was observed to aspirate, and the pharyngeal swallow was safe and functional in all cases. Three patients exhibited oesophageal motility disorders before treatment, while three more exhibited these disorders at the post-treatment assessments. Oral intake was most compromised one month post-treatment; at this time one patient was tube dependent, two required a single consistency diet and two had a diet requiring special preparation. At all other time-points patients were managing a normal or near-normal diet. Despite an absence of oropharyngeal dysphagia observed on VFSS, three patients reported moderate or severe swallowing difficulties one month post-treatment; these self-reported difficulties were no more than mild at follow-up assessments. Three additional patients reported the onset of moderate or severe swallowing difficulties at three and six months post-treatment. Patients who reported swallowing difficulties at one month post-treatment had all received a mean radiation dose to the oesophagus of ≥15.7Gy and a maximum dose to the oesophagus of ≥42Gy, however these relationships were no longer apparent at three and six months post-treatment. Patient-reported voice difficulties were variable, with the worst scores being reported at one month post-treatment for a subset of patients, who continued to report problems across voice-related physical, functional and emotional domains at three and six months post-treatment.
Conclusion
This is the first time that detailed swallowing and voice outcomes have been reported in patients with SCLC. Although patient numbers are small, this study identified discordance between observed swallowing function and patient-reported problems, which may have significant clinical implications for the management of patients with SCLC, as well as identify important issues for future research.
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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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P1.01-84 - Interaction of Lorlatinib with CYP2B6, CYP2C9, UGT, and P-gp Probe Drugs in Patients with Advanced Non-Small Cell Lung Cancer (ID 293)
09:45 - 18:00 | Author(s): Benjamin J Solomon
- Abstract
Background
Lorlatinib is a small-molecule anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of patients with ALK-positive advanced non-small cell lung cancer (NSCLC). Because lorlatinib is an inducer and inhibitor of various cytochrome P450 (CYP) enzymes and transporters, an evaluation of its effect on these substrates at steady state is warranted. A drug-drug interaction (DDI) sub-study was conducted in patients with advanced NSCLC to evaluate the net effect of these interactions.
Method
Probe drugs utilized included bupropion for CYP2B6, tolbutamide for CYP2C9, acetaminophen for uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT), and fexofenadine for P-glycoprotein-1 (P-gp). Thirty-two patients (to have at least 6 evaluable patients per probe drug) were administered a single dose of a probe drug alone on Day −2 to determine plasma exposure of the probe drug alone. Starting on Cycle 1 Day 1, patients began lorlatinib tablets 100 mg daily. On Cycle 1 Day 15, another single dose of the same probe drug was administered concurrently with lorlatinib.
Result
Co-administration of lorlatinib 100 mg with bupropion, a sensitive CYP2B6 probe drug, decreased bupropion geometric mean plasma AUCinf and Cmax by 25% and 27%, respectively. For tolbutamide, a sensitive CYP2C9 probe drug, lorlatinib decreased tolbutamide AUCinf and Cmax by 43% and 15%, respectively. Likewise, for acetaminophen, a sensitive UGT substrate, lorlatinib decreased acetaminophen AUCinf and Cmax by 45% and 28%, respectively. Finally, for fexofenadine, a sensitive P-gp substrate, lorlatinib decreased fexofenadine AUCinf and Cmax by 67% and 63%, respectively.
Conclusion
Critical steady-state–based DDI evaluations can be conducted in patients with cancer in carefully designed studies. Per FDA guidance, strong, moderate, and weak inducers are drugs that decrease the AUC of sensitive index substrates by ≥80%, ≥50% to <80%, and ≥20% to <50%, respectively. Based on these criteria, lorlatinib behaved as a net weak inducer of CYP2B6, CYP2C9, and UGT; and a net moderate inducer of P-gp. The results of this sub-study can help guide recommendations for dose modifications when lorlatinib is given concomitantly with drugs that are metabolized by these enzymes or transporters. Based on the current results, only drugs that are P-gp substrates of narrow therapeutic index may require dose adjustments when used concomitantly with lorlatinib.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-11 - ALKternate: A Proof of Concept Study in ALK-Rearranged NSCLC Alternating Lorlatinib with Crizotinib After Disease Progression (Now Available) (ID 2043)
10:15 - 18:15 | Author(s): Benjamin J Solomon
- Abstract
Background
Standard frontline therapy for patients with advanced ALK-NSCLC has rapidly evolved to 2nd generation ALK TKIs based on superior survival. Regardless, resistance to treatment is inevitable. Most will receive multiple lines of TKIs +/- chemotherapy before eventually dying from the disease.
Lorlatinib is a 3rd generation ALK TKI active against a broad range of acquired ALK kinase domain (KD) resistance mutations. A recent report demonstrated re-sensitisation to crizotinib by the lorlatinib ALK resistance mutation L1198F. Increased knowledge of resistance mechanisms is key to overcoming and preventing its emergence.
Based on knowledge of the varying patterns of resistance to different ALK TKIs, ALKternate will test the hypothesis that treatment with alternating TKIs will re-equilibrate the selection pressure for enrichment of resistant clones. This hypothesis has been tested preclinically in accompanying abstracts #2072 and #2074.
Method
ALKternate is a proof of concept open label multi-centre translational study alternating lorlatinib (100mg OD) with crizotinib (250mg BD) (Figure 1. including eligibility).
The aim is to identify whether this fixed alternating schedule of ALK TKI is: safe; feasible and active, resulting in prolonged systemic and intracranial disease control via delaying the emergence of ALK TKI resistance. A secondary aim is to investigate whether plasma ALK-dependent and independent resistance profiles can be used to monitor therapy effectiveness.
The primary outcome measure is time to treatment failure (TTTF) with alternating therapy. Secondary end points include best OR, PK analysis, PFS, DCR (systemic and CNS) after lorlatinib induction and the first cycle of alternating therapy, OS, toxicity, PROs and QOL measures. Plasma ctDNA and proteomic biomarkers will be analysed.
Enrolled patients must demonstrate disease control after induction lorlatinib to continue alternating therapy. Imaging occurs more frequently initially (Figure 1.), before 12 weekly after two alternating cycles in those with disease control.
Status: Trial in Progress. Enrollment began Q3 2019, ethics approval NSLHD ETH00389.
Figure 1. ALKternate trial schema
Result
Section not applicable
Conclusion
Section not applicable
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P2.01-17 - CANOPY-1: Phase 3 Study of Canakinumab/Placebo+Pembrolizumab+Platinum-Chemotherapy in Untreated Stage IIIB-IV NSCLC Pts (ID 1209)
10:15 - 18:15 | Author(s): Benjamin J Solomon
- Abstract
Background
Interleukin-1β (IL-1β) inhibition with canakinumab reduced the incidence of and mortality due to lung cancer among patients with atherosclerosis in CANTOS trial. Inhibition of IL-1β driven inflammation may lead to a tumor microenvironment more susceptible to anti-PD-(L)1 therapies. Recent studies have shown that low levels of CRP at baseline or decreased levels over time correlated with improved responses to anti-PD-(L)1 agents, providing rationale for combination of canakinumab and Pembrolizumab (PEM).
Method
CANOPY-1 (NCT03631199) is a double-blind, randomized, placebo (Pb)-controlled, phase III trial to determine efficacy and safety of PEM + platinum-based chemotherapy (Ctx) ± canakinumab in untreated stage IIIB/IIIC-IV squamous and non-squamous NSCLC pts. It is a 2 part study- In Part 1 [open-label safety run-in with 3 cohorts of ~9 pts each to confirm recommended phase 3 canakinumab regimen], pts will receive canakinumab 200 mg s.c (Q3W) + PEM 200 mg i.v (Q3W) + platinum-based Ctx [Cohort A (non-squamous), carboplatin (CBCDA) + pemetrexed (PTX); Cohort B (non-squamous), cisplatin + PTX; Cohort C (squamous or non-squamous), CBCDA + paclitaxel]. In Part 2 [with ~600 pts) to evaluate efficacy and safety of canakinumab combination], pts will be randomized to receive canakinumab/Pb + PEM + platinum-based Ctx (non-squamous, CBCDA or cisplatin + PTX; squamous, CBCDA + paclitaxel or nab-paclitaxel). PEM and platinum-based Ctx will be administered at their approved doses. Randomization (1:1) will be stratified by PD-L1 status, region and histology. In both parts, pts will receive 4 cycles of induction therapy (canakinumab/Pb + PEM + Ctx) followed by maintenance therapy (PEM + canakinumab/Pb +/- PTX) until progressive disease. Primary objectives: confirm recommended phase 3 regimen for canakinumab combination (Part 1), compare PFS and OS between treatment arms (Part 2). Secondary objectives (Part 1 and 2): ORR, DCR, safety, PK and DOR.
Result
Section not applicable
Conclusion
Section not applicable
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PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)
- Event: WCLC 2019
- Type: Plenary Session
- Track:
- Presentations: 1
- Now Available
- Moderators:Giorgio Vittorio Scagliotti, Ramon Rami-Porta
- Coordinates: 9/09/2019, 08:00 - 10:15, Barcelona (2005)
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PL02.08 - Registrational Results of LIBRETTO-001: A Phase 1/2 Trial of LOXO-292 in Patients with RET Fusion-Positive Lung Cancers (Now Available) (ID 964)
08:00 - 10:15 | Author(s): Benjamin J Solomon
- Abstract
- Presentation
Background
No targeted therapy is currently approved for patients with RET fusion-positive non-small cell lung cancer (NSCLC). LOXO-292 is a highly selective RET inhibitor with activity against diverse RET fusions, activating RET mutations and brain metastases. Based on initial data from LIBRETTO-001, LOXO-292 received FDA Breakthrough Designation for the treatment of RET fusion-positive NSCLC in August 2018.
Method
This global phase 1/2 study (87 sites, 16 countries) enrolled patients with advanced RET-altered solid tumors including RET fusion-positive NSCLC (NCT03157128). LOXO-292 was dosed orally in 28-day cycles. The phase 1 portion established the MTD/RP2D (160 mg BID). The phase 2 portion enrolled patients to one of six cohorts based on tumor type, RET alteration, and prior therapies. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, CNS ORR, CNS DoR, PFS, OS, safety and PK.
Result
As of 17-June 2019, 253 RET fusion-positive NSCLC patients were treated. The primary analysis set (PAS) for LOXO-292 registration, as defined with the US FDA, consists of the first 105 consecutively enrolled RET fusion-positive NSCLC patients who received prior platinum-based chemotherapy; 58 patients (55%) also received prior anti PD-1/PD-L1 agents. The majority of PAS responders have been followed for ≥6 months from first response. Of the remaining 148 patients, 79 had previously been treated with platinum-based chemotherapy, 55 did not receive prior platinum-based chemotherapy and 14 did not have measurable disease at baseline.
Conclusion
Among PAS patients, the investigator-assessed ORR was 68% (95% CI 58-76%, n=71/105, 2 PRs pending confirmation). Responses did not differ by fusion partner or the type or number of prior therapies, including chemotherapy, anti PD-1/PD-L1 agents and multikinase inhibitors with anti-RET activity. The median DoR was 20.3 months (95% CI 13.8-24.0) with a median follow-up of 8 months; as evidenced by the wide confidence interval, this DoR estimate is not statistically stable due to a low number of events (16 of 69 confirmed responders). The intracranial ORR was 91% (n=10/11: 2 confirmed CRs, 8 confirmed PRs) for patients with measurable brain metastases at baseline.
The ORR in efficacy evaluable treatment naïve RET fusion-positive NSCLC patients was 85% (95% CI 69-95%, n=29/34, 7 PRs pending confirmation). In the safety data set of all 531 patients, 5 treatment-related AEs occurred in ≥15% of patients: dry mouth, diarrhea, hypertension, increased AST and increased ALT. Most AEs were grade 1-2. Only 9 of 531 (1.7%) patients discontinued LOXO-292 for treatment-related AEs.
LOXO-292 had marked antitumor activity in RET fusion-positive NSCLC patients and was well tolerated. These data will form the basis of an FDA NDA submission later this year.
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YI01 - First Time Attendee Session (ID 107)
- Event: WCLC 2019
- Type: Young Investigator Session
- Track: Young Investigators
- Presentations: 1
- Now Available
- Moderators:Antonio Calles Blanco, Alan D Sihoe
- Coordinates: 9/07/2019, 07:00 - 08:30, Dublin (1997)
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YI01.04 - Congratulations, Your Abstract Has Been Accepted, and Now? - Tips and Tricks to Prepare a Presentation for WCLC (Now Available) (ID 3693)
07:00 - 08:30 | Presenting Author(s): Benjamin J Solomon
- Abstract
- Presentation
Abstract
This presentation will provide a practical guide about how to prepare and deliver an effective and engaging presentation at WCLC. Tips and suggestions will be provided for oral presentations, miniorals, posters and E-posters.
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