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Conor E Steuer
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MA01 - Oligometastatic Disease (ID 114)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Anne Marie Clasina Dingemans, Matthias Guckenberger
- Coordinates: 9/08/2019, 10:30 - 12:00, Copenhagen (1980)
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MA01.02 - Lung Stereotactic Body Radiotherapy and Concurrent Immunotherapy: A Multi-Center Safety and Toxicity Analysis (Now Available) (ID 597)
10:30 - 12:00 | Author(s): Conor E Steuer
- Abstract
- Presentation
Background
Radical treatment of metastases with stereotactic body radiotherapy (SBRT) in patients with advanced malignancies is an emerging treatment paradigm. SBRT is increasingly used in patients receiving immune checkpoint inhibition (ICI); however, limited toxicity data for this treatment approach exists. The purpose of this study was to evaluate the safety and tolerability of lung SBRT with concurrent ICI.
Method
Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SABR without ICI were included as a reference cohort. Treatment-related adverse-effects (AE) occurring within 30 days (acute) and 180 days (subacute) of SBRT were graded via CTCAE v5.0.
Result
110 patients were included; 47 received SBRT with concurrent ICI (49 SBRT courses, 61 lesions) between August 2015 and January 2019. 63 received SBRT without ICI (68 courses, 79 lesions). For the SBRT+ICI cohort, median age at treatment was 64 years, median follow-up was 6.7 months. 70% were lung, 15% were melanoma, 6.4% were from head and neck primaries. 90% were treated for metastatic consolidation/oligo-progression, 10% received SBRT for locally advanced/recurrent disease. 65.3% of patients received prior RT. 36.7% received prior lung RT, 40% of which were overlapping. 67% received ICI monotherapy, 16% ICI/chemotherapy, and 16% ICI/ICI combinations. 24.5% received ICI between SBRT fractions; 38.8% received ICI both before and after SBRT. Grade 3 (G3) and any grade pneumonitis rates were 8.2% and 30.6%; there were no G4-5 events. ICI was discontinued due to toxicity in 22.4% of patients. Receipt of ICI/ICI combinations increased the risk of any grade pneumonitis (62.5% vs 24.4%, p=0.04); but not G3 pneumonitis. Risk of G3 pneumonitis was higher in the SBRT+ICI vs SBRT alone cohort (8.2 vs 0%, p=0.03); but not any grade pneumonitis (30.6% vs 29.9%, SBRT+ICI vs SBRT p=0.75). Median time to onset was 3.4 months from end of SBRT in both groups. Risk of G3 and any grade pneumonitis was not predicted by ICI agent, timing of ICI administration, prior RT, prior lung RT, lesion centrality, number of target lesions, or smoking status. Overall acute G3+ AE rates were 2% (SBRT+ICI) and 0% (SBRT). Subacute G3+ AEs occurred in 26.5% (SBRT+ICI) and 2.9% (SBRT) of patients.
Conclusion
Concurrent ICI, especially ICI/ICI combinations, increased the risk of G3 pneumonitis with lung SBRT. However, SBRT+ICI appears safe and tolerable compared to SBRT alone. Strategies integrating SBRT and ICI warrant additional investigation.
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MA21 - Non EGFR/MET Targeted Therapies (ID 153)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Benjamin Besse, Michael Thomas
- Coordinates: 9/10/2019, 14:30 - 16:00, Vienna (2016)
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MA21.06 - Preliminary Phase 1 Results of U3-1402 — A Novel HER3-Targeted Antibody–Drug Conjugate—in EGFR TKI-Resistant, EGFR-Mutant NSCLC (Now Available) (ID 1720)
14:30 - 16:00 | Author(s): Conor E Steuer
- Abstract
- Presentation
Background
Treatment options are limited for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) resistant to EGFR tyrosine kinase inhibitors (TKIs), in particular osimertinib. Overall, 57%–83% of NSCLC tumors express human epidermal growth factor receptor 3 (HER3). Because signaling through HER3 is not an established mechanism of resistance to EGFR TKIs, treatment with an anti-HER3 antibody–drug conjugate (ADC) presents an approach to targeting diverse resistance mechanisms in EGFR-mutant NSCLC. U3-1402 is a HER3-targeted ADC with a fully humanized antibody, novel cleavable peptide-based linker, and topoisomerase I inhibitor payload. Here, we present the safety/tolerability and antitumor activity data from the dose-escalation phase of an ongoing, multicenter, phase 1 study (NCT03260491).
Method
Patients had locally advanced or metastatic EGFR TKI-resistant, EGFR-mutant NSCLC. Patients with stable brain metastases were eligible. Dose escalation was based on dose-limiting toxicities (DLTs) guided by a Bayesian logistic regression model. U3-1402 was administered every 3 weeks via intravenous infusion. Pretreatment tumor tissue was required for retrospective HER3 immunohistochemistry analysis. Next-generation sequencing analysis was performed on available tumor tissue. Primary objectives included safety, tolerability, and identification of the recommended dose for expansion (RDE).
Result
As of May 2019, 30 patients were enrolled across 4 doses (3.2 [n=4], 4.8 [n=9], 5.6 [n=12], and 6.4 [n=5] mg/kg). Thirteen patients (43%) have discontinued (progressive disease [n=9], clinical progression [n=1], consent withdrawal [n=2], adverse event [AE; n=1]). All 30 patients received prior EGFR TKIs, of which 28 (93%) received prior osimertinib, and 15 (50%) prior chemotherapy. Activating EGFR mutations were reported in all patients (Ex19del: 57%; L858R: 40%; L861Q: 3%). All 25 evaluable tumors demonstrated HER3 expression (median HER3 membrane H-score, 183 [range, 56–290]). History of central nervous system (CNS) metastases was reported in 15 patients (50%). Treatment-emergent AEs were reported in 29 patients (97%; 13 patients [43%] reported grade 3/4). Two DLTs (grade 3 febrile neutropenia and grade 4 platelet count decrease) were reported in 1 patient (5.6 mg/kg) and 3 DLTs (all grade 4 platelet count decrease) in 3 patients (6.4 mg/kg). Of patients with a history of CNS metastases, 9 have progressed (2 with CNS progression; 3 with both CNS and non-CNS progression). One patient without a history of CNS metastasis progressed with new CNS disease. Of 26 efficacy-evaluable patients, 6 had confirmed partial responses (2 each at 4.8, 5.6, and 6.4 mg/kg), including 2 patients with an EGFR C797S mutation. Median best percentage change in sum of diameters (SoD) was −25.7% (range, −82.6% to 13.3%), including decreases in SoD in patients with CDK4 amplification (–25.7% and –17.8%), HER2 amplification (–28.6%), and both CCNE1 amplification and PIK3CA mutation (–28.8%).
Conclusion
U3-1402 demonstrated tolerable safety and antitumor activity in this ongoing study. Antitumor activity of U3-1402 was seen in cancers with EGFR-mediated and other resistance mechanisms. These findings support the hypothesis that targeting HER3 with U3-1402 may provide clinical benefit to patients with EGFR-mutant NSCLC with diverse mechanisms of resistance. RDE evaluation is ongoing.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-08 - Integration of Durvalumab into the Treatment of Stage III Non-Small Cell Lung Cancer: Real-World Considerations (ID 1115)
09:45 - 18:00 | Author(s): Conor E Steuer
- Abstract
Background
Background: In 2017, the PACIFIC study demonstrated improvement in progression free survival, leading to FDA approval for the treatment of unresectable stage III non-small cell lung cancer (NSCLC) that has not progressed following concurrent platinum based chemoradiation (CRT). This study reports on practice patterns during the first year of adaptation of immunotherapy into the treatment paradigm for stage III NSCLC at a NCI designated Comprehensive Cancer Center.
Method
Methods: This retrospective study captured patients (pts) with unresectable NSCLC treated from 09/2017-10/2018 who referred to radiation oncology for definitive treatment. Clinical and treatment characteristics were extracted, including radiation dose parameters and information regarding durvalumab administration.
Result
Results: 48 pts with locally advanced NSCLC were referred for definitive radiation therapy. 17% were not eligible for concurrent CRT: of these, 6 received 60 Gy hypofractionated radiation alone, and 2 received 60-64 Gy with conventional fractionation. Forty (83%) received concurrent CRT (80% carboplatin/paclitaxel, 10% cisplatin/etoposide, 10% platinum/pemetrexed). Of the patients undergoing CRT, 32% did not go on to receive durvalumab due to the following factors: 25% due to unresolved grade 3 or higher toxicities, 25% due to relative contraindications to immunotherapy, 17% were lost to follow up, 8% due to disease progression, 8% due to active illicit drug use, 8% due to large tumor and potential risk for pneumonitis, and 8% received nivolumab. Twenty-seven (68% of pts receiving CRT, 56% of all referred pts) went on to receive durvalumab after completion of CRT. For these pts, the radiation dose parameters were as follows: median total dose of 60 Gy (range 60-66 Gy), median lung V20 of 22.7% (range 5.4-31.5%), median lung mean dose of 13.9 Gy (range 5.3-19.5 Gy), and median heart mean dose of 12.9 Gy (range .715 – 29.9 Gy). The median time from completion of radiation to start of durvalumab was 36 days (range 11-84). Restaging imaging with CT chest after completion of CRT was obtained at a median time point of 35 days. The median number of cycles of durvalumab was 5 (range 1-20). Of pts receiving durvalumab, 37% stopped before 1 year; 40% due to disease progression, 50% due to intolerable side effects, and 10% were lost to follow up.
Conclusion
Conclusions: Durvalumab was successfully integrated in a rapid fashion into the treatment paradigm for stage III NSCLC in this single institution experience, however only 56% of referred pts were ultimately able to receive durvalumab.
