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Matthew A Gubens
OA 17 - Immunotherapy II (ID 683)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
OA 17.01 - Pemetrexed-Carboplatin Plus Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC: KEYNOTE-021 Cohort G Update (ID 9059)
14:30 - 16:15 | Author(s): Matthew A Gubens
Cohort G of the multicenter, open-label, phase 1/2 KEYNOTE-021 study (ClinicalTrials.gov, NCT02039674) evaluated efficacy and safety of pembrolizumab + pemetrexed and carboplatin (PC) compared with PC alone as first-line therapy for patients with advanced nonsquamous NSCLC. At the primary analysis of cohort G (minimum follow up, 6 months; median, 10.6 months), pembrolizumab significantly improved ORR (estimated treatment difference, 26%; P=0.0016) and PFS (hazard ratio [HR], 0.53; P=0.010). The HR for OS was 0.90 (95% CI, 0.42‒1.91). In a subsequent analysis (median follow-up, 14.5 months), the HR for OS was 0.69 (95% CI, 0.36‒1.31). We present results from the May 31, 2017 data cutoff.
Patients with stage IIIB/IV nonsquamous NSCLC, no prior systemic therapy, and no EGFR mutation or ALK translocation were randomized 1:1 (stratified by PD-L1 TPS ≥1% versus <1%) to receive 4 cycles of carboplatin AUC 5 + pemetrexed 500 mg/m Q3W with or without pembrolizumab 200 mg Q3W. Pembrolizumab treatment continued for up to 2 years; maintenance pemetrexed was permitted in both arms. Eligible patients in the PC arm with radiologic progression could cross over to pembrolizumab monotherapy. Response was assessed by blinded, independent central review per RECIST v1.1. All P values are nominal (one-sided P<0.025).
123 patients were randomized. Median follow-up was 18.7 months (range, 0.8‒29.0 months). 40 of 53 (75%) patients in the PC arm who discontinued received subsequent anti-PD-1/anti-PD-L1 therapy (including 25 who received pembrolizumab in the on-study cross over). ORR was 57% with pembrolizumab + PC versus 32% with PC (estimated difference, 25%; 95% CI, 7%‒41%; P=0.0029). PFS was significantly improved with pembrolizumab + PC versus PC (HR, 0.54; 95% CI, 0.33‒0.88; P=0.0067) with median (95% CI) PFS of 19.0 (8.5‒NR) months versus 8.9 (6.2‒11.8) months. The HR for OS was 0.59 (95% CI, 0.34‒1.05; P=0.0344). Median (95% CI) OS was not reached (22.8‒NR) months for pembrolizumab + PC and 20.9 (14.9‒NR) months for PC alone; 18-month OS rates were 70% and 56%, respectively. Grade 3–5 treatment-related AEs occurred in 41% of patients in the pembrolizumab + PC arm versus 29% in the PC arm.
Over the course of the 3 analyses, the HR for OS continues to improve for pembrolizumab + PC versus PC (HR: 0.90 to 0.69 to 0.59). The significant improvements in PFS and ORR with pembrolizumab + PC versus PC first observed in the primary analysis have been maintained with longer follow-up (median, 18.7 months).
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.01-007 - ALK Testing Trends and Patterns Among Community Practices in the United States (ID 8654)
09:30 - 16:00 | Author(s): Matthew A Gubens
The CAP/IASLC/AMP molecular testing guidelines recommend ALK testing on patients with lung adenocarcinoma, regardless of clinical characteristics. FISH is the recommended assay to detect ALK rearrangement, however other assays, such as NGS and IHC, are available. There have been limited published data to assess adherence to ALK testing guidelines using large real-world data sources. The objective of this study was to assess real-world ALK testing patterns among community practices in the United States.
The Flatiron database provides real-world clinical data collected from EHRs used by US cancer care providers. The Flatiron network comprises ~15% of US cancer patients and is geographically and demographically diverse. Patients with ≥2 visits within the Flatiron Network after Jan 1, 2011, >=18 years of age, and an stage IIIB/IV NSCLC diagnosis from 2011 through 2017 Q1 were included in this analysis. Logistic regression was used to identify patient characteristics associated with receiving ALK testing.
Of 29,903 patients identified from community-based clinics (mean age: 71.6, 52.2% male), ALK testing rates have steadily increased over time from 32.2% in 2011 to 61.0% in 2016 for all NSCLC patients, and 41.0% in 2011 to 74.0% in non-squamous patients. Patients that are younger, no history of smoking, women and living in the West region were more likely to be tested for ALK. Patients with Medicaid insurance, recurrent disease and squamous histology were less likely to be tested. The most common first assay to test for ALK was FISH (70%) followed by NGS (8%), PCR (4%) and IHC (1%). The median time from specimen receipt by lab to test result ranged from 6 days (FISH) to 11 days (NGS). Patients who had NGS testing were more likely to initiate chemotherapy prior to test result (34% of patients tested with NGS) than FISH (20%). 1235 patients had at least one FISH and another ALK test, with the percent agreement between FISH and other assays (NGS, PCR, IHC) ranging from 92% to 97%.
Several patient characteristics predicted ALK testing indicating that some subgroups of patients may be under tested, according to guidelines. Consistent with guidelines, FISH was the most common assay and turnaround times from lab receipt to test result was under 2 weeks. There was a high agreement between FISH and NGS, indicating the potentially clinical utility of NGS, however NGS had also the longest turn around time and the highest proportion of patients initiating treatment prior to test results.
P1.01-008 - Real-World Patient Characteristics, Testing and Treatment Patterns of ALK+ NSCLC (ID 8681)
09:30 - 16:00 | Presenting Author(s): Matthew A Gubens
Based on clinical trials, ALK+ patients have been described as typically younger and never/former smokers, however patients enrolled in clinical trials may be different than those in the real-world. While the ALK positivity rate has been described as about 4% among all NSCLC patients, limited information is available on the positivity rates in patient subgroups. The objective of this study is to describe the real-world ALK positivity rates, patient characteristics and treatment patterns in ALK+ NSCLC patients.
The Flatiron database provides real-world clinical data collected from EHRs used by US cancer care providers. The Flatiron network comprises ~15% of US cancer patients and is geographically and demographically diverse. Patients with ≥2 visits within the Flatiron Network after Jan 1, 2011, ≥18 years of age, ≥1 ALK+ test result and an stage IIIB/IV NSCLC diagnosis from 2011 through 2017 Q1 were included in this analysis. Logistic regression was used to examine the association of ALK positivity and initiation of ALK inhibitor therapy based on patient characteristics. Survival model adjusting for censoring was used to estimate the time to ALK inhibitor order.
599 out of 15,551 ALK tested patients were identified to have an ALK positive test result, for a positivity rate of 3.9%. The ALK positivity rate varied by age (<65: 6.3% vs. ≥65: 2.9%), smoking status (no history of smoking: 11.6% vs. history of smoking: 2.3%), and histology (non-squamous: 4.0% vs. squamous: 1.8%). Factors associated with ALK positivity included younger age, academic practice, male, non-squamous histology, and no history of smoking. 78% of patients with ALK+ disease had evidence of an order for an ALK inhibitor after NSCLC diagnosis. The median time from test result to ALK inhibitor order was 24 days, with 42% of patients without an order for an ALK inhibitor within 90 days. Among patients with an order for an ALK inhibitor, 23% received chemotherapy prior to their ALK test result and 20% received chemotherapy after their test result but before the first order of ALK inhibitor. Patients diagnosed after 2014 and patients who received chemotherapy prior to the ALK test result were more likely to have an order for an ALK inhibitor.
The ALK positivity rate and patient characteristics in this real-world NSCLC population are consistent with clinical trials, with some subgroups having higher positivity rates. ALK inhibitors were the most frequently ordered treatment, however many patients had a delayed time to ordering the ALK inhibitor.