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Tarek Mekhail
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-06 - New Treatment Option for ES-SCLC: Patient Characteristics and Use of an Atezolizumab Regimen in the Real-World Setting (Now Available) (ID 2651)
08:00 - 18:00 | Author(s): Tarek Mekhail
- Abstract
Background
Results from the Phase III IMpower133 study (NCT02763579) were previously made public. Based on improvements in overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) who received atezolizumab plus carboplatin and etoposide (IMpower133 regimen) vs chemotherapy administered in the 1L setting, the NCCN added this regimen to its guidelines (category 1, preferred) on October 10, 2018. Accordingly, some providers began implementing this regimen in their clinical practice, creating a unique opportunity to characterise its early and broad use in a real-world setting.
Method
Patients with ES-SCLC who started treatment within 90 days of initial diagnosis and had a confirmed administration of atezolizumab with carboplatin or cisplatin and etoposide (atezo regimen) on or after September 25, 2018, were included from the de-identified Flatiron Health electronic health records–derived database, representing > 280 US cancer clinics (≈ 800 sites of care). Treatment data were analysed through April 30, 2019. Broad use was defined as treatment with the atezo regimen outside of several main clinical trial restrictions (ECOG PS ≥ 2, abnormal laboratory values, cisplatin use or as 2L treatment). Frequencies and percentages are reported. Monthly uptake was defined as the percentage of ES-SCLC patients starting 1L therapy each month who were treated with the atezo regimen.
Result
Uptake of the atezo regimen increased from 10% in October 2018 to 46% in February 2019 (before FDA approval on March 18, 2019) and 66% in April 2019 (after FDA approval); 143 patients were identified, 92% of whom had ES-SCLC at initial diagnosis (Table). The atezo regimen was used broadly among 46% of patients (18% with ECOG PS ≥ 2, 18% with an abnormal laboratory value, 1% on cisplatin, 17% as 2L ES-SCLC treatment). The median time from ES-SCLC diagnosis to start of the atezo regimen was 16 days for 1L patients and 78 days for 2L patients. Patients treated with the atezo regimen in the 1L were administered atezolizumab at a median of 8 days after start of chemotherapy; those treated in the 2L were typically administered atezolizumab immediately at the start of the line.
Conclusion
This real-world analysis demonstrates the broad use of the atezo regimen, with nearly half of patients treated outside of several main IMpower133 trial restrictions. Further, a rapid uptake of the regimen even before FDA approval underscores its impact on changing clinical practice and the high unmet need of this patient population.
Table. Characteristics of Patients Treated With the Atezolizumab Plus Carboplatin/Cisplatin and Etoposide Regimen in Routine Clinical Care
Patients, n
143
Treated prior to FDA approval (March 18, 2019), n (%)
101 (71)
Median age at ES-SCLC diagnosis (IQR), years
67 (61, 73)
Aged ≥ 65 years at ES-SCLC diagnosis, n (%)
90 (63)
Female, n (%)
71 (50)
White, n (%)
100 (70)
Smoking history, n (%)
137 (96)
Stage at initial diagnosis, n (%)
LS
7 (5)
ES
132 (92)
Unknown
4 (3)
ECOG PS, n (%)a
0 or 1
76 (53)
2+
26 (18)
Unknown
41 (29)
Radiation therapy, n (%)b
14 (10)
LS setting, n
7
ES setting, n
7
Regimen, n (%)
Atezolizumab, carboplatin, etoposide
141 (99)
Atezolizumab, cisplatin, etoposide
2 (1)
Line of therapy of atezo regimen in ES setting, n (%)
1L
119 (83)
2L
24 (17)
Median time from ES-SCLC diagnosis to start of line of therapy containing atezo regimen (IQR), days
1L
16 (11, 26)
2L
78 (59, 98)
Median time from ES-SCLC diagnosis to first administration of atezo within line (IQR), days
1L
24 (14, 27)
2L
78 (59, 98)
Abnormal baseline laboratory value, n (%)c
26 (18)
1L, first line; 2L, second line; atezo, atezolizumab; ECOG, Eastern Cooperative Oncology Group; FDA, US Food and Drug Administration; IQR, interquartile range; LS, limited stage; PS, performance status.
a ECOG PS value closest to within −30 to +7 days of treatment start.
b Includes radiation therapy to chest following initial diagnosis of SCLC, including concurrent radiation therapy with systemic chemotherapy, chemotherapy followed by radiation therapy, up-front palliative radiation therapy to the chest or for superior vena cava syndrome.
c Abnormal values defined as those not meeting the following definitions: absolute lymphocyte count ≥ 500/μL, lymphocyte count ≥ 500/μL, absolute neutrophil count ≥ 1500 cells/μL, platelet count ≥ 100,000/μL, hemoglobin ≥ 9.0 g/dL, aspartate aminotransferase ≤ 5 × upper limit of normal (ULN), alanine aminotransferase ≤ 5 × ULN, alkaline phosphatase ≤ 5 × ULN, serum bilirubin ≤ 1.25 × ULN, serum creatinine ≤ 1.5 × ULN, serum calcium ≤ 12 mg/dL.
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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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P1.01-112 - Phase 3, Randomized, Double-Blind Trial of First-Line Pembrolizumab With or Without Lenvatinib in Metastatic NSCLC: LEAP-007 (ID 1406)
09:45 - 18:00 | Presenting Author(s): Tarek Mekhail
- Abstract
Background
The anti–PD-1 antibody pembrolizumab, as monotherapy or in combination with chemotherapy, is the standard of care for most patients with untreated metastatic non–small-cell lung cancer (NSCLC) with no EGFR/ALK aberrations. Lenvatinib is an anti-angiogenic multireceptor tyrosine kinase inhibitor that enhanced the antitumor activity of PD-1 inhibitors in vitro and showed clinical activity in combination with pembrolizumab in patients with metastatic NSCLC in a recent open-label, phase 1b/2 study (NCT02501096). LEAP-007 (NCT03829332) further evaluates the safety and efficacy of pembrolizumab plus lenvatinib in patients with metastatic NSCLC.
Method
This randomized, double-blind, phase 3 trial enrolls previously untreated adult patients with stage IV NSCLC and PD-L1 TPS ≥1% without sensitizing genetic aberrations. Patients are randomized 1:1 to pembrolizumab 200 mg Q3W plus lenvatinib 20 mg daily or pembrolizumab plus matching placebo, stratified by geographic region (East Asia vs other), ECOG PS (0 vs 1), and TPS (1%–49% vs ≥50%). Treatment continues until verified disease progression (PD), unacceptable AE, illness, withdrawal of consent, noncompliance, or administrative reason. Radiographic imaging occurs Q9W from randomization through 54 weeks, then every 12 weeks until confirmed PD or start of a new anticancer regimen, and is assessed by blinded independent central review (BICR) using RECIST v1.1. Primary outcomes are PFS (RECIST v1.1 by BICR) and OS. Secondary outcomes include ORR (RECIST v1.1 by BICR), safety (AEs graded according to NCI CTCAE v4.0), and health-related quality of life. PFS and OS will be analyzed using the Kaplan-Meier method and stratified log-rank test; hazard ratios will be estimated using a stratified Cox regression model. ORR will be analyzed using the stratified Miettinen and Nurminen method, and differences will be estimated using the stratified Miettinen and Nurminen method with strata weighting by sample size. Target enrollment is 620 patients from 165 sites. As of April 5, 2019, 13 patients have been screened.
Result
Not applicable
Conclusion
Not applicable
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-14 - Phase 3 Trial of Sitravatinib Plus Nivolumab vs Docetaxel for Treatment of NSCLC After Platinum-Based Chemoimmunotherapy (ID 614)
10:15 - 18:15 | Author(s): Tarek Mekhail
- Abstract
Background
Sitravatinib is a tyrosine kinase inhibitor (TKI) that targets multiple closely-related receptor tyrosine kinases (RTKs), including the split RTKs VEGFR-2 and KIT as well as the TAM (TYRO3, AXL, and MER) RTKs. Inhibition of the split RTKs may reduce immunosuppressive regulatory T (Treg) cells and myeloid‑derived suppressor cells (MDSCs) within the tumor microenvironment (TME), while inhibition of TAM RTKs may, in addition to promoting depletion of MDSCs, repolarize tumor associated macrophages towards the M1 phenotype that is associated with secretion of pro-inflammatory cytokines. Given these pleiotropic immune‑stimulating effects, sitravatinib may augment the antitumor immune response of nivolumab in patients (pts) with non-small cell lung cancer (NSCLC). An ongoing Phase 2 study demonstrates clinical activity of this combination in pts with metastatic non-squamous NSCLC after progression on a checkpoint inhibitor (CIT).
Method
This randomized, open-label, Phase 3 study (N=664) compares the efficacy and safety of sitravatinib in combination with nivolumab vs docetaxel in pts with advanced non-squamous NSCLC who have radiographically documented disease progression on or after platinum-based chemotherapy in combination with CIT. Pts are randomized (1:1) to receive sitravatinib administered orally once daily in continuous 28-day cycles at 120 mg combined with nivolumab IV at 240 mg every 2 weeks or 480 mg every 4 weeks vs treatment with docetaxel 75 mg/m2 IV every 3 weeks. Patients will be stratified based on duration of previous CIT treatment, ECOG performance status, and presence of brain metastases at baseline. Key eligibility criteria include duration of treatment of CIT for at least 4 months, discontinuation of prior treatment with CIT < 90 days prior to the date of randomization, and absence of symptomatic or uncontrolled brain metastases. The primary endpoint is Overall Survival (OS). Key secondary endpoints include safety and tolerability, ORR, PFS, PROs, and PK. OS will be analyzed using Kaplan-Meier methods and the stratified log-rank test to estimate and compare the median OS between the two treatment arms with 95% CI. An IDMC will be established to review safety at regular intervals and to review efficacy data at the planned interim analysis for futility and possible sample size adjustment based on OS.
Recruitment begins May 2019.
NCT number NCT03906071
Result
Section not applicable
Conclusion
Section not applicable.
