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Bilal Piperdi
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MA25 - Precision Medicine in Advanced NSCLC (ID 352)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Sebastian Defranchi, Karen Kelly
- Coordinates: 9/10/2019, 14:30 - 16:00, Dublin (1997)
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MA25.01 - Pembrolizumab Plus Chemotherapy for Advanced NSCLC Without Tumor PD-L1 Expression: Pooled Analysis of KN021G, KN189 and KN407 (Now Available) (ID 1399)
14:30 - 16:00 | Author(s): Bilal Piperdi
- Abstract
- Presentation
Background
Randomized studies have demonstrated that pembrolizumab plus chemotherapy improves OS, PFS, and ORR compared with chemotherapy alone in patients with advanced NSCLC regardless of tumor PD-L1 expression level. We present a post hoc pooled analysis of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression (ie, TPS <1%), representing an area of unmet need.
Method
Patients enrolled in KEYNOTE-021 cohort G (nonsquamous; NCT02039674), KEYNOTE-189 (nonsquamous; NCT02578680), and KEYNOTE-407 (squamous; NCT02775435) were included. Patients with nonsquamous NSCLC were randomized to pemetrexed-platinum with or without pembrolizumab; those with squamous NSCLC were randomized to carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab. OS, PFS, and ORR were evaluated for the pooled intent-to-treat population. Response was assessed per RECIST v1.1 by blinded independent central review. Across studies, PD-L1 expression was assessed centrally using PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA). Analyses were descriptive.
Result
Of 1298 patients enrolled across the 3 trials, 428 (33%) had PD-L1 TPS <1% (pembrolizumab plus chemotherapy, n=243; chemotherapy alone, n=185) and were included in this analysis. 52% had nonsquamous histology, 63% had ECOG PS of 1. Median (range) follow-up at data cutoff was 10.2 (0.1‒34.9) months. OS, PFS, and ORR were improved with pembrolizumab plus chemotherapy versus chemotherapy alone (Table). Grade ≥3 AEs (all-cause) occurred in 68% of patients receiving pembrolizumab plus chemotherapy versus 72% receiving chemotherapy alone. Immune-mediated AEs and infusion reactions occurred in 26% who received pembrolizumab plus chemotherapy versus 12% who received chemotherapy alone.
ConclusionPembrolizumab + Chemotherapy
n=243
Chemotherapy
Alonen=185
Median (95% CI) OS, mo
19.0 (15.2–24.0)
11.0 (9.2–13.5)
Hazard ratio (95% CI)
0.56 (0.43–0.73)
Median (95% CI) PFS, mo
6.5 (6.2–8.5)
5.4 (4.7–6.2)
Hazard ratio (95% CI)
0.67 (0.54–0.84)
ORR, % (95% CI)
46.9% (40.5%–53.4%)
28.6% (22.3%–35.7%)
Difference (95% CI)
18.3% (9.0%–27.1%)
Our results highlight the clinically meaningful efficacy benefit and acceptable safety profile of pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced NSCLC and no PD-L1 expression. Benefit was consistent with that observed in the overall study populations, suggesting pembrolizumab plus chemotherapy should be considered standard-of-care first-line therapy for all patients with NSCLC, irrespective of PD-L1 expression.
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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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P1.01-05 - Phase I Study of Inhaled 5-Azacytidine (5-Aza) in Patients (Pts) with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2368)
09:45 - 18:00 | Author(s): Bilal Piperdi
- Abstract
Background
Our previous study in an endo-bronchial NSCLC murine model suggested that aerosolized 5-Aza could inhibit cancer growth, prolong survival, and induce re-expression of methylated tumor suppressor genes. This is the first in human phase I study of 5-Aza delivered by inhalation in pts with advanced NSCLC.
Method
Main inclusion criteria: Stage IV or recurrent NSCLC with predominantly lung involvement, ≥1 prior systemic therapy, ECOG PS 0-1, and good pulmonary function. Pts were treated with inhaled 5-Aza daily, D1 to D5 and D15 to D19 of a28-day cycle. Initial dose escalation used an accelerated titration scheme, followed by a 3 + 3 dose escalation and de-escalation design. The starting dose was 15mg/m2 (derived from preclinical studies that showed it to be a safe and DNA demethylating dose), followed by 30 and 45 mg/m2. The primary objective was to determine the MTD and toxicity (especially pulmonary toxicity). Secondary objectives included PK, methylation profiles pre and post 5-Aza (bronchoscopy), efficacy (RECIST 1.1), PFS and OS.
Result
From 3/2015 to 12/2017, 8 pts were treated with 3 escalating doses of inhaled 5-Aza, including 2 at the highest level of 45mg/m2. Median follow up: 15m. Median age 70, 62.5% female, 62.5% blacks, all PS=1, 87.5% adenocarcinoma with 1 EGFR and 2 KRAS mutants, 62.5% active/former smoker, mean number of prior therapies: 3 lines. Mean treatment cycles: 3.4 (1-12). No treatment related adverse events were reported. No DLTs were observed. Preliminary PK study indicated no detectable 5-Aza in the blood. No objective response was observed, 37.5% (3/8) had stable disease (SD). Median PFS and OS were 2 m and 12 m respectively. One pt had SD > 17 m and received a total of 2 cycles, whereas another KRAS-mutant pt had SD >29 m and received a total of 12 cycles.
Conclusion
Inhaled 5-Aza was well-tolerated with no treatment-related toxicity. The administration of 5-Aza by inhalation was feasible for multiple cycles in pts with advanced NSCLC without any significant pulmonary toxicity. The methylation studies in bronchial epithelium are ongoing and will be presented. Our results suggest that inhaled 5-Aza may represent a novel and safe therapeutic strategy for patients with lung-confined malignant and/or premalignant lesions. Clinical trial information: NCT02009436. Supported by NIH CA154755
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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: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-15 - Rates of Systemic Anticancer Therapy (SACT) for Advanced Non-Small Cell Lung Cancer (aNSCLC) in the US, 2011–2018 (ID 2704)
09:45 - 18:00 | Author(s): Bilal Piperdi
- Abstract
Background
The SACT options for aNSCLC continue to increase each year with approvals of more effective therapies that improve long-term outcomes, such as immunotherapies (IO). Our aim was to examine trends in SACT rates from 2011-2018 for patients with aNSCLC and no known EGFR/ALK aberrations at US community oncology practices.
Method
We used the nationwide Flatiron Health EHR-derived database (data cutoff: 31Jan2019), which incorporates oncologist-defined, rule-based lines of therapy. Adults with aNSCLC diagnosis date from Jan2011-Jun2018, inclusive, with recorded EHR activity ≤90 days after diagnosis, were eligible. Patients with known EGFR/ALK-positive tumors, or nonsquamous histology (NSQ) with unknown or untested EGFR/ALK status, were excluded. We summarized no-treatment and first-line (1L) SACT rates as a proportion of aNSCLC diagnosed from 2011-2018, while limiting 2L and 3L SACT rates to aNSCLC diagnoses from 2011-2016 in order to have sufficient follow-up. Results were stratified by NSQ and squamous (SQ) histology, as well as by pre-IO and post-IO years of aNSCLC diagnosis, defined broadly as 2011-2014 and 2015+, respectively, based on the earliest IO approval for 2L therapy in Mar2015.
Result
The figure depicts 1L, 2L, and 3L SACT rates by year of aNSCLC diagnosis for EGFR/ALK-negative NSQ and for SQ. For NSQ, the pre-IO and post-IO no-treatment rates were 28% (2286/8246) and 22% (2520/11,639), respectively. For SQ, the pre-IO and post-IO no-treatment rates were 34% (1781/5200) and 26% (1549/6040).
Conclusion
For both EGFR/ALK-negative NSQ and SQ aNSCLC, 1L SACT rates are trending upward, with no-treatment rates showing substantial drops in the post-IO (versus pre-IO) period. The 2L and 3L SACT rates are variable for both NSQ and SQ; and SACT rates for NSQ tend to be substantially greater than for SQ across all lines of therapy and years of diagnosis.
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P1.16-42 - Real-World Trends in Systemic Anticancer Therapy (SACT) for Squamous Advanced NSCLC (aNSCLC) in the US, 2011–2018 (ID 2768)
09:45 - 18:00 | Author(s): Bilal Piperdi
- Abstract
Background
The SACT options for aNSCLC continue to increase each year with approvals of more effective therapies that improve long-term outcomes, as seen with immunotherapies (IO). Our aim was to examine real-world trends in SACT distribution and sequence from first- to second-line (1L-2L) for squamous aNSCLC from 2011-2018 at US community oncology practices.
Method
This study used the nationwide Flatiron Health de-identified, EHR-derived database (cutoff: 31Jan2019). Eligible patients were adults who initiated 1L SACT from Jan2011-Jun2018 for aNSCLC with squamous histology, excluding patients with known EGFR/ALK-positive tumors. Descriptive analyses included patients receiving ≥1 SACT dose, assigning all SACT regimens to mutually exclusive classes in hierarchical order (combination regimens assigned by highest component), from highest to lowest: (1) PD1/PD-L1 inhibitor (anti-PD1/L1)-based, (2) EGFR/ALK TKI-based, (3) platinum-based chemotherapy combination with vascular endothelial growth factor inhibitor (PBC+VEGF), (4) PBC only, (5) single agent chemotherapy, (6) others. The 2L regimens were examined for patients with 1L SACT initiation only through 2017 to enable sufficient follow-up. Results were stratified by years and by pre-IO and post-IO years of 1L initiation, defined as 2011-2014 and 2015-2018, respectively, based on the earliest IO approval for 2L therapy in Mar2015.
Result
For 1L therapy, in the pre-IO period, most patients were prescribed PBC (80%), and post-IO, most patients were prescribed PBC (68%) or anti-PD1/L1 (21%). Among patients prescribed 1L therapy, the percentages who received 2L therapy were 44%-53% following 1L PBC and 25%-37% following 1L anti-PD1/L1, with 19% of 2017 1L anti-PD1/L1 starts still on 1L therapy (table).
Conclusion
PBC remain the most common 1L SACT prescribed through mid-2018 for patients with squamous aNSCLC at US community oncology practices. Prescribing of PD1/PD-L1 inhibitors as 1L has gradually increased since regulatory approval starting in 2015. Approximately one-half of patients with squamous aNSCLC prescribed 1L PBC are treated with 2L therapy.
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P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.16-17 - Real-World Trends in Systemic Therapy for Nonsquamous EGFR/ALK-Negative Advanced NSCLC (aNSCLC) in the US, 2011–2018 (ID 2744)
10:15 - 18:15 | Author(s): Bilal Piperdi
- Abstract
Background
Systemic anticancer therapy (SACT) options for aNSCLC continue to increase each year with approvals of more effective therapies that improve long-term outcomes, as seen with immunotherapies (IO). We aimed to examine real-world trends in SACT distribution and sequence from first- to second-line (1L-2L) for EGFR/ALK-negative nonsquamous aNSCLC from 2011-2018 at US community oncology practices.
Method
This study used the nationwide Flatiron Health de-identified, EHR-derived database (cutoff: 31Jan2019). Eligible patients were adults with aNSCLC, nonsquamous histology with known EGFR/ALK-negative status, who initiated 1L SACT from Jan2011-Jun2018. SACT regimens were assigned to mutually exclusive classes in hierarchical order, from highest to lowest: (1) PD1/PD-L1 inhibitor (anti-PD1/L1)-based, (2) EGFR/ALK TKI-based, (3) platinum-based chemotherapy (PBC) combination with vascular endothelial growth factor inhibitor (PBC+VEGF), (4) PBC only, (5) single agent chemotherapy, (6) others. 2L regimens were examined for patients initiating 1L SACT only through 2017 to enable sufficient follow-up. Results were stratified by year and by pre-IO/post-IO years of 1L initiation, defined as 2011-2014/2015-2018, respectively, based on earliest IO approval for 2L therapy in Mar2015.
Result
For 1L, in the pre-IO period, most patients were prescribed PBC (53%) or PBC+VEGF (30%), and post-IO, most were prescribed PBC (43%), anti-PD1/L1 (25%), or PBC+VEGF (23%). Among patients prescribed 1L therapy, the percentages who received 2L therapy were 50%-62% post-1L PBC; 56%-62% post-1L PBC+VEGF; and 28%-38% post-1L anti-PD1/L1 (table). A substantial percentage (25%) of those initiating 1L anti-PD1/L1 in 2017 were still on therapy at cutoff.
Conclusion
Changing trends in real-world prescribing of 1L-2L SACT for EGFR/ALK-negative nonsquamous aNSCLC from Jan2011-Jun2018 include decreasing use of PBC in 1L and 2L, decreasing use of PBC+VEGF in 1L, and, increasing use of PD1/PD-L1 inhibitors in 1L and 2L. Slightly more than one-half of patients with nonsquamous aNSCLC prescribed 1L PBC are subsequently treated with 2L therapy.
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P2.16-41 - Pembrolizumab for Previously Treated, PD-L1–Expressing Advanced NSCLC: Real-World Time on Treatment and Overall Survival (ID 2364)
10:15 - 18:15 | Author(s): Bilal Piperdi
- Abstract
Background
Information from real-world clinical settings remains limited regarding outcomes of pembrolizumab therapy for advanced NSCLC. Our aim was to examine real-world time on treatment (rwToT) and overall survival (OS) for patients prescribed pembrolizumab monotherapy for previously treated, PD-L1–expressing advanced NSCLC, thus clinically similar to patients in the KEYNOTE-10 (KN010) trial.
Method
This retrospective study used Flatiron Health’s nationally representative EHR-derived database to identify adult patients with histologically confirmed advanced NSCLC and PD-L1 tumor proportion score (TPS) ≥1% previously treated with platinum-containing chemotherapy (and appropriate TKI if nonsquamous NSCLC with EGFR/ALK aberration). Eligible patients initiated pembrolizumab monotherapy from January 1, 2016, to May 31, 2018; those with <6 months of follow-up were excluded. Kaplan-Meier (KM) rwToT and OS were calculated.
Result
Median follow-up was 15.6 months (range 6.0–32.8 months). Of 281 eligible patients (56% male), median age was 68 years; 36% had squamous NSCLC; 10% brain metastases; and 57%, 18%, and 25% ECOG performance status 0–1, ≥2, and unknown, respectively. Baseline characteristics were similar across PD-L1 TPS distributions. The table summarizes rwTOT and OS by PD-L1 TPS categories.
Conclusion
Real-world patients treated with pembrolizumab monotherapy after platinum-containing chemotherapy for PD-L1–expressing advanced NSCLC experienced rwToT and OS benefits similar to findings in a clinical trial setting, validating KN010 findings and approved indication in second line.
