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C. Aggarwal
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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:G. Purkalne, J. Von Pawel
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 2
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MA16.10 - Lung-MAP (S1400) Lung Master Protocol: Accrual and Genomic Screening Updates (ID 3995)
15:20 - 15:26 | Author(s): C. Aggarwal
- Abstract
- Presentation
Background:
Lung-MAP (S1400), is a master protocol that incorporates genomic testing of tumors through a next generation sequencing (NGS) platform (Foundation Medicine) and biomarker-driven (matched) therapies for patients with squamous cell lung cancer (SCCA) after progression on first-line chemotherapy.
Methods:
The Lung-MAP trial, activated June 16, 2014, includes 3 matched- and 1 non-match study. Matched studies include: S1400B evaluating taselisib, a PI3K inhibitor, S1400C evaluating palbociclib, a CDK 4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The non-match study S1400I tests nivolumab + ipilimumab vs. nivolumab. Two studies have closed: S1400E evaluating rilotumumab an HGF monoclonal antibody + erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match pts, closed 12/18/2015.
Results:
From June 16, 2014 to June 15, 2016, 812 pts were screened and 292 pts registered to a study: 116 to S1400A, 27 to S1400B, 53 to S1400C, 32 to S1400D, 9 to S1400E and 55 to S1400I. Demographics: Screening was successful for 705 (87%) of screened eligible pts. Median age 67 (range 35-92); male 68%; ECOG PS 0-1 88%, PS 2 10%; Caucasian 85%, Black 9%, other 5%; never/former/current smokers 4%/58%/36%. Table 1 displays biomarker prevalence; 39% of pts matched; 33.9%, 4.8%, and 0.3% with 1, 2, and all 3 biomarkers, respectively. Tumor mutation burden (TMB) was available for 636 (90.4%) of eligible pts. The distribution of TMB is: 126 (19.8%) low (≤5 mutations Mb), 415 (65.1%) intermediate (6-19 mutations/Mb), and 96 (15.1%) high (≥20 mutations/Mb). The median TMB was 10.1.
Conclusion:
Genomic screening is feasible as part of this master protocol designed to expedite drug registration, confirm anticipated prevalence of targeted alterations in SCCA and reveal intermediate or high TMB in most (80.2%) pts. Treatment results are not yet available as patients continue to accrue. Clinical trial information: NCT02154490Total FGFR CDK PIK3CA FGFR (15.9%) 12.9% 2.4% 0.6% CDK (18.8%) 14.6% 1.8% PIK3CA (8.8%) 6.4% Biomarker prevalence and overlap.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-019 - Imaging of Anti-PD1 Therapy Response in Advanced Non-Small Lung Cancer (ID 6316)
14:30 - 14:30 | Author(s): C. Aggarwal
- Abstract
Background:
Therapy with immune checkpoint inhibitors can lead to unconventional tumor responses and autoimmune-mediated adverse effects resulting from immune activation. Here we sought to determine pseudo-progression and radiologically-evident anti-PD1 therapy mediated adverse events in routine clinical management in the advanced non-small cell lung cancer (NSCLC) population.
Methods:
A retrospective study was conducted of all adult NSCLC patients treated with anti-PD1 agents at our institution. Electronic medical records were reviewed to determine clinical assessment of anti-PD1 therapy response and imaging reports at restaging. Patients that did not have available follow-up imaging or clinical data while on anti-PD1-therapy were excluded from the study. Patient imaging exams with clinically suspected tumor pseudo-progression at 1[st] re-staging were analyzed to determine if subsequent imaging demonstrated pseudo-progression or true progression. The incidence of radiographically-evident adverse events attributed to anti-PD1 therapy by the oncologist were noted.
Results:
A total of 228 patients were started on anti-PD1 therapy at our institution, of which a total of 166 were evaluable. Of the evaluable patients, 80% of those received nivolumab and the remaining 20% received pembrolizumab. The overall response rate (complete response + partial response) was 23% at 1[st] restaging. Of these patients, 22 patients were suspected of pseudo-progression due to tumor enlargement and/or development of new lesions during the 1[st] 4-6 weeks of therapy and were maintained on anti-PD1 therapy. Of these patients, there were 5 confirmed cases of pseudo-progression at subsequent restaging. Radiologically-evident adverse events occurred in less than 5% of the population, primarily manifesting as pneumonitis.
Conclusion:
Pseudo-progression and radiographically-evident adverse events are important but uncommon occurrences in the setting of anti-PD1 therapy for advanced NSCLC.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-028 - Outcomes of Nivolumab in Elderly Patients (pts) with Non-Small Cell Lung Cancer (NSCLC) (ID 5084)
14:30 - 14:30 | Author(s): C. Aggarwal
- Abstract
Background:
In randomized trials of nivolumab in NSCLC, less than 10% of pts were ≥75 years old, and all had Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1. The effectiveness of nivolumab in elderly pts with NSCLC treated in routine practice has not been previously described.
Methods:
We conducted a retrospective cohort study of pts with advanced NSCLC treated with nivolumab outside of clinical trials at the University of Pennsylvania between March 2015 and March 2016. Logistic regression and Cox proportional hazards models were used to evaluate the association of age (≥75 vs. <75 years) with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), adjusting for ECOG PS (0-1 vs. ≥2), sex, smoking history [heavy (≥10 pack-years) vs. light/never (<10 pack-years)], and number of prior systemic therapies (1 vs. ≥2).
Results:
Of 175 pts treated with nivolumab, 43 (25%) were ≥75 years old and 42 (24%) had ECOG PS ≥2. Ninety-five pts (54%) were female, 147 (84%) had heavy smoking history, and 81 (46%) had received ≥2 prior systemic therapies. ORR was 19.4%, with median PFS and OS of 2.1 and 6.5 months, respectively. Age ≥75 years was not associated with ORR (OR 1.0, 95% CI 0.4-2.5; p=0.97), PFS (HR 0.71, 95% CI 0.5-1.1; p=0.12), or OS (HR 0.8, 95% CI 0.5-1.4; p=0.4; Figure 1). ECOG PS ≥ 2 was associated with lower ORR (7.1% vs. 23.3%; OR 0.25, 95% CI 0.07 – 0.88; p=0.03), inferior PFS (median 1.8 vs. 2.3 months; HR 1.9, 95% CI 1.3 – 2.8; p=0.001), and inferior OS (median 3.6 vs. 7.8 months; HR 2.6, 95% CI 1.6 – 4.1; p<0.001). Figure 1
Conclusion:
In a large NSCLC cohort treated outside of clinical trials, elderly pts gained similar benefit from nivolumab compared to younger pts. Pts with poor performance status had inferior outcomes regardless of age.
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P3.02c-029 - Immune-Related Adverse Events and Their Effect on Outcomes in Patients (pts) with Non-Small Cell Lung Cancer (NSCLC) Treated with Nivolumab (ID 5206)
14:30 - 14:30 | Author(s): C. Aggarwal
- Abstract
Background:
Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs). While the incidence of irAEs in routine practice and their effect on outcomes have been well characterized in melanoma, a similar analysis has not been previously reported in NSCLC pts treated with anti-programmed death 1 (PD-1) therapy.
Methods:
We conducted a retrospective cohort study of pts with advanced NSCLC who received nivolumab outside of clinical trials between March 2015 and March 2016 at the University of Pennsylvania. irAEs were graded using the Common Terminology Criteria for Adverse Events version 4.0. Data collected included demographics, timing and treatment of irAEs, and dates of disease progression and death or last follow-up. To analyze the effect of irAEs on progression-free survival (PFS) and overall survival (OS), landmark analyses were used beginning from 3 months after start of treatment. Pts who reached the PFS or OS endpoints prior to 3 months were excluded. Cox proportional hazards models were used to assess for differences in PFS and OS according to the occurrence of an irAE, adjusting for age, sex, and Eastern Cooperative Oncology Group Performance Status (ECOG PS).
Results:
175 pts received a median of 5 cycles of nivolumab (range, 1-24, IQR, 3-9). Median age was 68 years (range, 33-88, IQR, 60-74). Forty-six percent of pts were male; 5% had an ECOG PS ≥ 2. Twenty-eight pts (16%) experienced an irAE of any grade and 6 (3%) had a grade 3/4 irAE. Median time to onset of the irAE was 3 cycles (range, 1-18, IQR, 2-6). Of the pts who experienced an irAE, 14 (50%) were treated with systemic corticosteroids. The most common irAEs were hypothyroidism/hyperthyroidism (n=8), pneumonitis (n=6; three grade 4), colitis (n=4; one grade 3), dermatitis (n=4), and arthritis (n=2). Less common irAEs (n=1 each) included hepatitis (grade 4), aseptic meningitis (grade 3), immune thrombocytopenia, and severe hypoalbuminemia that improved with steroids. Overall response rate was 19.4% (34 of 175), and median PFS and OS were 2.1 and 6.5 months, respectively. After adjusting for age, sex, and ECOG PS, landmark analyses revealed no difference in PFS (HR 1.3, 95% CI 0.4-3.8, p=0.7) or OS (HR 0.9, 95% CI 0.3-2.7, p=0.9) stratified by the presence or absence of an irAE.
Conclusion:
In NSCLC pts treated with nivolumab in typical practice, irAEs of any grade were uncommon, and grade 3/4 irAEs were rare. The occurrence of irAEs was not associated with PFS or OS.
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P3.02c-069 - Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) Predicts Outcomes with Nivolumab in Non-Small Cell Lung Cancer (NSCLC) (ID 5218)
14:30 - 14:30 | Author(s): C. Aggarwal
- Abstract
Background:
The NLR, a marker of systemic inflammation, has been associated with outcomes in multiple cancers. In patients (pts) with metastatic melanoma treated with ipilimumab, pre-therapy NLR < 5 has been associated with improved progression-free survival (PFS) and overall survival (OS). However, the utility of NLR as a marker of outcomes in pts with NSCLC treated with programmed-death 1 (PD-1) inhibitors is not known.
Methods:
We conducted a retrospective cohort study of pts with advanced NSCLC treated with nivolumab off clinical trials at the University of Pennsylvania between March 2015 and March 2016. NLR was calculated from complete blood counts obtained within two weeks of starting nivolumab. Pts were dichotomized based on a NLR <5 or ≥ 5. We calculated PFS and OS using the Kaplan-Meier method and used multivariate Cox proportional hazards models to adjust for sex, age, histology (squamous vs. non-squamous), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0-1 vs. ≥ 2), smoking history [heavy (≥10 pack-years) vs. light/never (<10 pack-years)], and number of prior systemic therapies (1 vs. ≥ 2).
Results:
175 pts received a median of 5 cycles of nivolumab (range, 1-24; IQR 3-9). Median age was 68 years (range 33-88, IQR 60-74), 46% of pts were male, 75% were white, 25% had an ECOG PS ≥ 2, and 46% had ≥ 2 prior systemic therapies. Eighty-four percent of pts had a ≥10 pack-year smoking history, and 76% had non-squamous histology. Median baseline NLR was 5.5 (IQR, 3.1 – 9.4), with NLR < 5 in 73 pts (42%) and NLR ≥ 5 in 102 patients (58%). Through the date of this analysis (June 1, 2016), disease progression had occurred in 124 pts (71%), and 92 pts (53%) had died, resulting in median PFS and OS of 2.1 and 6.5 months, respectively. After controlling for the aforementioned clinical and demographic factors, pts with baseline NLR<5 had significantly improved PFS (median 2.8 vs. 1.9 months; adjusted HR=0.70, 95% CI: 0.50-0.99; p = 0.04) and OS (median 8.4 vs. 5.5 months; adjusted HR=0.54, 95% CI: 0.34-0.84; p = 0.007) compared to pts with NLR ≥ 5.
Conclusion:
Pre-therapy NLR is independently associated with PFS and OS in advanced NSCLC pts treated with nivolumab. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in predicting outcome in the context of other biomarkers of PD-1 therapy.
