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Taofeek Owonikoko
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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): Taofeek Owonikoko
- 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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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-17 - Phase I/II Study of Nivolumab and Vorolanib in Patients with Refractory Thoracic Tumors (ID 2443)
09:45 - 18:00 | Author(s): Taofeek Owonikoko
- Abstract
Background
Single-agent nivolumab has limited efficacy in thoracic tumors. The antitumor activity of VEGF TKIs is typically attributed to their effect on angiogenesis; however, emerging data suggest these agents can modulate the immune system, especially in the immune suppressive microenvironment. Preliminary results in multiple solid tumors demonstrated clinical benefit when nivolumab was added to anti-angiogenic agents albeit with increased toxicities. Vorolanib was designed to improve the safety profile without compromising efficacy. No dose-limiting toxicities (DLTs) from vorolanib were reported in multiple single-agent phase I trials.
Method
NCT03583086 is an ongoing multi-institutional, phase I/II study of nivolumab and vorolanib in patients with thoracic tumors who have failed at least one prior line of therapy. A standard 3+3 dose escalation design was planned with three doses of vorolanib (200, 300, and 400 mg once-daily) and 240 mg nivolumab every two weeks to determine the maximum tolerated dose. Phase II will evaluate the response rate in five cohorts: PD-1/PD-L1 naïve non-small cell lung cancer (NSCLC), PD-1/PD-L1 primary refractory (defined as progression on PD-1/PD-L1 therapy within 12 weeks), NSCLC patients with acquired resistance (achieved at least stable disease and then progressed) to PD-1/PD-L1, thymic carcinoma, and small cell lung cancer patients who have progressed on prior platinum-based chemotherapy. Exploratory correlatives will assess changes in the innate and adaptive immune responses after treatment.
Result
Phase I enrolled 10 patients (eight NSCLC and two thymic cancers); one patient was not evaluable for DLT and replaced. No DLTs were observed in three patients at the first dose level of 200 mg. Vorolanib was escalated to 300 mg, and elevated ALT (Grade 3) occurred in two of six patients just beyond the DLT period but deemed clinically significant; thus, 200 mg vorolanib with 240 mg nivolumab is being evaluated in expansion cohorts. The most common adverse events were elevated ALT, AST, and lipase, diarrhea, and fatigue; most were Grade 1/2. Grade 4 hyperglycemia and elevated lipase and Grade 3 elevated serum amylase occurred in one patient each. In seven efficacy-evaluable patients (2 immunotherapy naïve NSCLC; 3 NSCLC with prior immunotherapy; 2 thymic cancer), two partial responses were observed (1 PD-1/PD-L1 naive NSCLC and 1 thymic cancer patient); the NSCLC patient was also PD-L1 negative. Three NSCLC patients with prior PD-1/PD-L1 inhibitors had tumor regression; two of these had acquired resistance and the other was primary refractory to prior immunotherapy.
Conclusion
The combination of 200 mg vorolanib and 240 mg nivolumab was generally well tolerated. Clinical activity was observed in both PD-1/PD-L1 naïve patients and those treated with prior immunotherapy. Final phase I results and available phase II data will be presented.
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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): Taofeek Owonikoko
- 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.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-03 - Inter-Fraction Variability of 18-FDG PET During Lung SBRT and the Effect of Systemic and Immunotherapy: Results of a Prospective Pilot Study (Now Available) (ID 154)
09:45 - 18:00 | Author(s): Taofeek Owonikoko
- Abstract
Background
18-FDG PET/CT has been used to inform prognosis, response to treatment, adaptive planning, and target volume delineation in NSCLC. Changes in PET characteristics, such as inter-fraction variation of 18-FDG uptake during a course of ablative radiation, and how PET metrics respond to systemic agents during SBRT, are unknown. This study prospectively characterized key metabolic parameters during lung SBRT, an important factor for biology-guided radiotherapy (BgRT).
Method
Patients treated with lung SBRT of 50Gy in 5 fractions for early-stage NSCLC or lung metastases were eligible. Three PET/CTs were acquired per protocol: within 2 weeks of treatment start (PET1), between fractions 1 and 2 (PET2), and fractions 4 and 5 (PET3). The primary endpoint was inter-fraction variability. FDG-PET parameters including maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), and derived metrics were extracted and compared longitudinally; where change between PET1 and PET2 is denoted as PET1-2. PET parameters were extracted using a MIMVISTA (v6.8.3) work station. Lesions were segmented with individualized location-based window settings. The effect of co-variates on each static (PET1, PET2, PET3) and change metric (PET1-2, PET2-3, PET1-3) were determined for each PET parameter. Continuous and categorical variables were compared by non-parametric methods with Spearman and Kruskal-Wallis tests. Clinical trial NCT03493789.
Result
14 patients who completed treatment as prescribed, with 17 total target lesions, were included. Treatment indications were: 5 (35.7%) medically-inoperable, 2 (14.3%) medically operable, 1 (7.1%) recurrent, 2 (14.3%) metastatic consolidation, 4 (28.6%) metastatic progression. 7 (50%) received prior systemic therapy, 4 (28.6%) received immunotherapy with 2 (14.3%) given concurrently. In aggregate, SUVmax did not significantly change over the SBRT course. Average SUVmax change from PET1 to PET2 (PET1-2) was -8.2% (p=0.51), -7.0% for PET1-3 (p=0.52), and 1.3% for PET2-3 (p=0.92). SUVmean, [SUVmax/SUVmean], and normalized parameters of [SUVmax/liver SUVmean] and [SUVmean/liver SUVmean] were similarly stable over the treatment course. Multiple PET2, PET1-2, and PET2-3 parameters were significantly related to systemic therapy, immunotherapy, and timing of administration. There were no significant interactions between age, sex, number of target lesions, target location, lesions centrality, smoking status, and static and change metrics for each PET parameter.
Table 1. Correlation between treatment variables and median SUVmax for each PET/CT study and each inter-fraction SUVmax change between PET/CTs. PET1 PET2 PET3 PET1-2 PET1-3 PET2-3 Co-variates Median SUVmax p-value Median SUVmax p-value Median SUVmax p-value SUVmax change p-value SUVmax change p-value SUVmax change p-value Systemic therapy (no vs yes) 7.52 vs 5.76 0.336 8.24 vs 4.91 0.021 6.12 vs 7.26 0.700 0.79 vs -1.46 0.034 0.13 vs -0.40 0.700 -2.46 vs 1.98 0.005 Immunotherapy (no vs yes) 7.46 vs 5.99 0.752 7.92 vs 4.82 0.058 7.26 vs 3.50 0.461 0.65 vs -3.11 0.027 0.14 vs -1.40 0.598 -1.14 vs 0.58 0.073 Concurrent administration (no vs yes) 5.99 vs 10.67 0.365 7.44 vs 6.30 0.821 6.12 vs 10.91 0.308 0.58 vs -4.37 0.024 0.10 vs -1.48 0.428 -0.40 vs 4.38 0.113
Conclusion
Serial 18-FDG PET imaging during lung SBRT demonstrated minimal variability of key parameters. FDG uptake at PET2, change from baseline, and between fractions, were related to systemic therapy, immunotherapy, and timing of administration. Mechanism of PET parameter variability, and its impact of on oncologic outcomes require investigation; prospective evaluation of BgRT is ongoing.
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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-20 - NRG Oncology/Alliance LU005: A Phase II/III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab in LS-SCLC (Now Available) (ID 2670)
10:15 - 18:15 | Author(s): Taofeek Owonikoko
- Abstract
Background
Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation (ClinicalTrials.gov Identifier: NCT03811002).
Method
Patients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab beginning concurrently with thoracic radiation, and continued every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), sex, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). It is hypothesized that the addition of atezolizumab will yield a hazard ratio of 0.62 for PFS, for a sample size of 280 patients in the phase II portion of this study. The overall sample size for phase II/III will be 506, with the OS analysis designed to provide at least 85% power to detect a hazard ratio of 0.71 at a 1-sided significance level of 0.025. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. This study includes a robust translational science component including blood and tissue based assays to further understand which patients may benefit most from immunotherapy.
Result
This study activated in May 2019 and is currently enrolling patients.
Conclusion
NRG Oncology/Alliance LU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. The estimated date of study completion is May 2024.
*Authors Higgins and Ross are co-first authors and contributed equally to this work.
