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Nasser Hanna
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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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P1.01-67 - Ph I/II Carboplatin, Nab-Paclitaxel and Pembrolizumab for Advanced NSCLC (HCRN LUN13-175): Outcomes by Nab-Paclitaxel Dose (ID 530)
09:45 - 18:00 | Author(s): Nasser Hanna
- Abstract
Background
Combination chemotherapy and immunotherapy have significantly improved survival for patients with treatment-naïve advanced non-small cell lung cancer (NSCLC). We sought to evaluate the safety and efficacy of adding pembrolizumab to a standard regimen at the time of study development, nab-paclitaxel and carboplatin. Safety data from phase I have been reported, and phase II commenced with the same chemotherapy doses and flat dosing of pembrolizumab at 200 mg.
Method
Patients with treatment-naïve, stage IIIB/IV NSCLC AJCC 7 (all histology), any PDL1, no EGFR or ALK, ECOG 0-1, received carboplatin AUC 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3wks. Co-primary endpoints were progression-free survival (PFS) and response rate (RR). PDL1 was assessed prior to treatment and from biopsies obtained after cycle 4.
Result
46 patients enrolled, 14 on phase I and 32 in phase II, from June 2015–July 2018. Accrual stopped after data was presented from similar phase III trials. 43 were evaluable for the primary endpoints. Median age was 65 years, 48% female, 45% adenocarcinoma, 94% current/former smokers, 9% brain metastases. PDL1 expression (TPS) by <1%, 1-49%, and ≥ 50% cutoffs was 44%, 28%, and 28%, respectively. ORR was 28%. Median PFS was 5.6 months (CI, 4.2-10.5 mo). Median OS was 15.7 mo (CI 11.1-22.3 mo). There was no statistical differences in PFS or OS outcomes by PDL1 status. Paired PDL1 results from pre- and post-treatment biopsies were available in 8 patients. PDL1 status changed categories in 4/8 samples (n=3, 0% to positive; n=1, 99% to 0%). The most common grade 3-4 adverse events (AEs) were neutropenia (64%), anemia (31%), thrombocytopenia (24%), leukopenia (16%) and fatigue (11%). Other notable AEs included rash (58%), diarrhea (47%), neuropathy (22%), arthralgia (18%), transaminitis (13%), and myalgia (11%). 18% discontinued treatment due to AEs. In an exploratory analysis, there was no difference in median PFS for those receiving total nab-paclitaxel dose of 400–799 mg/m2 compared to ≥800 mg/m2 (6.2 mo vs. 8.2 mo, p=0.62).
Conclusion
Although the study did not meet its pre-specified endpoints of PFS 9 months and RR of 50%, results were similar to previously reported phase III Keynote 407 (squamous histology). Despite hematologic toxicity, the combination could safely be administered, and outcomes were similar for those receiving moderate doses of nab-paclitaxel compared to those with an average of at least 200 mg/m2 per cycle.
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P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.18-05 - ChemoXRT W/ Consolidation Pembrolizumab in Unresectable Stage III NSCLC: Long-Term Survival Update and Analysis of Post-Progression Therapy (Now Available) (ID 2765)
09:45 - 18:00 | Author(s): Nasser Hanna
- Abstract
Background
Consolidation PD-1/PD-L1 inhibition following chemoradiation is a new standard of care for patients with stage III NSCLC. 3-year survival rates in patients receiving consolidation PD-1/PD-L1 have not been previously reported. In addition, the response to subsequent chemotherapy or immunotherapy in patients who experienced disease progression following consolidation PD-1/PD-L1 has also not been previously reported.
Method
This is a phase II, single-arm, multi-center trial of consolidation pembrolizumab 200mg IV every 3 weeks for up to a year following concurrent chemoradiation in patients with unresectable stage III NSCLC. This analysis provides the first-ever report of 3-year overall survival (OS) estimates with consolidation PD-1. In addition, treatment details for patients who experienced progression of disease on or after consolidation pembrolizumab are described.
Result
Median follow is 31.1 months (range 1.2-42.4). Median OS is 35.8 months (95% CI, 24.2 -not estimable). One, two, and three-year OS estimates are 81.1%, 62%, and 49.5%. Of 37 patients reported to have progressive disease (PD), subsequent treatment data were available for 35. Twenty-four received additional systemic therapy, and 11 received no subsequent systemic treatment. Fifteen experienced PD during pembrolizumab, 18 after pembrolizumab (and 4 had missing data). The best response to any systemic therapy (n=24) was 3 partial responses (PR), 9 stable disease (SD), and 12 PD. Chemotherapy was given to 21 patients and 1 patient each received erlotinib, ponatinib, and an investigational agent. Best response to chemo was 2 PR, 6 SD, and 13 PD. 11 patients received pemetrexed with 2 SD and 9 PD; 6 patients received a single agent taxane with 1 SD and 5 PD. 5 patients received combination therapy with 1 PR, 3 SD, and 1 PD. 3 patients received gemcitabine with 1 PR and 2 PD. 6 of 24 patients received subsequent PD-1 or PD-L1 inhibitors; the best response to immunotherapy was 1 PR and 5 PD. The PR was a patient who had completed pembro consolidation 14 months prior to PD and subsequently was retreated with pembro at the time of biopsy-proven recurrence (PD-L1 TPS was 90%). He responded after 3 cycles of pembro and has maintained this response for 13+ cycles.
Conclusion
The 3-year OS estimate indicates that nearly half of all patients treated with consolidation pembrolizumab may be long-term survivors. For patients with disease progression after consolidation pembrolizumab, response rates with chemotherapy are similar to what is expected in the 2nd line setting with 38% experiencing disease control for a period of time. Only 1 of 6 patients re-challenged with a checkpoint inhibitor responded, but this patient has maintained a durable response lasting 13+ cycles.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-24 - An Open-Label Randomized Phase II Study of Combining Osimertinib With and Without Ramucirumab in TKI-Naïve EGFR-Mutant Metastatic NSCLC (ID 851)
10:15 - 18:15 | Author(s): Nasser Hanna
- Abstract
Background
Osimertinib, a third-generation EGFR inhibitor, has become the first-line therapy for patients with metastatic EGFR-mutant NSCLCs since 2018. Osimertinib is well-tolerated, therefore, it opens opportunities to be combined with other therapeutic agents to enhance the treatment outcome. In preclinical models, it has been shown that upregulated VEGF signaling mediates acquired resistance to EGFR therapies. In xenograft models, combination of anti-VEGF medications with EGFR inhibitors were significantly more effective than erlotinib or gefitinib alone. Ramucirumab, a monoclonal antibody targeting VEGF receptor 2, is approved with docetaxel in as second line treatment for NSCLCs. In clinical trial evaluations, the phase 3 RELAY trial (NCT02411448) studying ramucirumab plus erlotinib in patients with metastatic untreated EGFR-mutant NSCLC patients showed a statistically significant improvement in progression-free survival in the combination group compared to erlotinib alone. A phase I study of osimertinib with ramucirumab (NCT02789345) demonstrated safety and feasibility of this combination. With strong preclinical and clinical evidence showing dual inhibition of VEGF/EGFR signaling prolongs progression-free survival for EGFR-mutant lung cancers, and demonstrated safety, we are conducting a phase 2 trial to evaluate the osimertinib ramucirumab combination’s efficacy in treatment-naïve EGFR-mutant NSCLC.
Method
The OSI+RAM trial is a randomized phase 2 study with the primary endpoint being progression-free survival in osi+ram group as compared to osimertinib monotherapy group. The major inclusion criteria include patients with metastatic NSCLC harboring EGFR mutations (L858R/Exon 19 del). The major exclusion criteria include prior anti-EGFR or anti-VEGF treatments. Patients with stable CNS metastasis are allowed. Based on the results from erlotinib bevacizumab (NEJ026) study, we expect an improvement of PFS from 18.9 months to 29.7 months, corresponding to a hazard ratio of 0.65. The trial plans to enroll total of 150 patients, with 100 allocating to osi+ram arm and 50 to osimertinib monotherapy. Total of 9 study sites in the USA are planned. Hoosier Cancer Research Network will facilitate the execution of the trial. The trial protocol has received IND exemption from US FDA and has been approved by IRB at MD Anderson Cancer Center. The first subject is expected to be enrolled in May 2019. A planned interim analysis will be performed after the first 75 subjects are enrolled. NCT03909334.
Result
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Conclusion
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