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Ajeet Gajra
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.20 - Impact of Antibiotics During Immune Checkpoint Inhibitor (ICI) Therapy for Non-Small Cell Lung Cancer: A Real-World Analysis (ID 3567)
00:00 - 00:00 | Presenting Author(s): Ajeet Gajra
- Abstract
Introduction
Conflicting evidence exists regarding the impact of antibiotic (ATB) use on effectiveness of ICIs among patients with cancer due to ATB effect on gut microbiota. In non-small cell lung cancer (NSCLC), these studies are mostly retrospective, single-institution series or unplanned subset analyses of clinical trials with no adjustments made for multiple potential confounders. There is significant heterogeneity across studies regarding ATB exposure, ICI line of therapy, types of ICI (PD/L-1 with/without CTLA-4 inhibitor), and outcomes reported (progression free [PFS], overall survival [OS]). A recent meta-analysis (Lurienne et al, 2020) reported that PFS was reduced by 1.2 months in patients exposed to ATB. Thus, this US claims-based analysis aimed to assess the real-world impact of ATB use on time to discontinuation of first-line (1L) ICIs, (surrogate of PFS) in patients with advanced NSCLC.
Methods
Patients with ≥1 non-diagnostic hospital claim or 2 outpatient claims indicating NSCLC (plus 1 claim indicating metastasis) from January 1, 2015 to September 30, 2019, ≥1 claim for ICI therapy (limited to PD/L-1 agent in 1L), and ≥1 month pre and post earliest ICI claim were identified from Symphony Health longitudinal prescription and medical claims; patients with claims indicative of SCLC, secondary malignancies, and participation in a clinical trial were excluded. Patients were classified as having ATB use (anytime within 30 days pre and post ICI initiation) and no ATB (no claims for ATB in 30 days prior and during ICI therapy). Patient characteristics were summarized for each ATB group by frequencies for categorical variables and measures of centrality and spread for continuous variables; comparisons across groups were made by chi-square and Mann-Whitney tests. Median duration and 95% confidence intervals (CI) of ICI therapy was estimated by Kaplan-Meier estimator, adding 28 days to last claim for nivolumab or atezolizumab and 21 days for pembrolizumab.
Results
Among the 307 NSCLC patients included, 74 (24%) had ATB use, and 233 (76%) had no ATB use. Median age at diagnosis was similar across groups (65.5-66 years; P=0.79), while those with ATB use had a greater preponderance of females (54% vs 39%; P=0.02). Median follow-up from diagnosis was 13.7 months. Most common ATBs were β-lactams (45%), quinolones (39%), macrolides (23%), and tetracyclines (12%). ATBs were given a median of 7 days with 23% treated with >1 course for ATBs. Nivolumab (31% vs 35%), pembrolizumab (39% vs 31%), and atezolizumab (3% vs 8%) use were similar across those with and without ATB use, respectively (all P>0.05). Median durations of ICI therapy were similar among those with (6.9 months, 95% CI 5.4-9.9 months) and without ATB use (8.9 months, 95% CI 6.9-12.1 months; P=0.21).
Conclusion
ATB use is common among NSCLC patients prior to and early during ICI therapy. ATB use did not have a statistically significant impact on time to ICI discontinuation, a measure of disease progression in a real-world US cohort of patients with NSCLC. However, the magnitude of decrement is similar to that reported in recent meta-analyses. Additional research is warranted to assess the true impact of ATB use with ICI in NSCLC.
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P09.54 - Pneumonitis Following Durvalumab: A Real-World Analysis in Patients with Lung Cancer and Other Tumor Types (ID 3569)
00:00 - 00:00 | Presenting Author(s): Ajeet Gajra
- Abstract
Introduction
Durvalumab, a PDL-1 inhibitor is the standard of care as consolidation therapy after chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC) in the United States (US). Immune-mediated pneumonitis occurs with all checkpoint inhibitors, however patients with lung cancer may be particularly susceptible. In the PACIFIC trial supporting approval of durvalumab for this indication, any pneumonitis was reported in 34% of durvalumab-treated patients vs. 24% of placebo-treated patients. Pneumonitis represented 34% of all adverse events (AEs) in the study and led to treatment discontinuation in 6% durvalumab-treated patients (Antonia et al, NEJM 2018). Durvalumab is also approved in the US for recurrent urothelial cancer, but only 1% of patients experienced pneumonitis in the supporting trial. We conducted an analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate post-marketing cases of pneumonitis reported in patients treated with durvalumab for NSCLC vs. other tumor types.
Methods
The FAERS database, which contains anonymized reports of product-related AEs classified using the Medical Dictionary for Regulatory Activities and categorized as serious or non-serious, was queried for cases of pneumonitis in patients treated with durvalumab for oncology indications from the Food and Drugs Administration (FDA) approval date (May 1, 2017) through June 30, 2020. Cases occurring outside the US and cases for which the indication was not specified were excluded. The indication for use, reported demographics and AE outcomes were collected. The association of pneumonitis with indication and AE seriousness was evaluated by Chi-square test, using a two-sided α=0.05 to determine statistical significance. Median age in each subgroup was compared using the Mann-Whitney U test.
Results
Of the 733 durvalumab-associated AE cases retrieved, (532 [73%] for NSCLC, 201 [27%] for other tumor types), a total of 130 reports of any pneumonitis were identified. Pneumonitis accounted for 122 of 532 (23%) of all AEs reported in NSCLC vs. 8 of 201 (4%) in other tumor types (p<0.01). A greater proportion of pneumonitis cases were categorized as serious compared to non-pneumonitis cases (125 of 130 [96%] vs. 421 of 603 [70%], p<0.01). There was no difference between pneumonitis and non-pneumonitis cases in reported deaths (25 of 130 [19%] vs. 101 of 603 [17%]) or hospitalizations (57 of 130 [44%] vs. 242 of 603 [40%]). The median age of patients in pneumonitis cases was older than patients in non-pneumonitis cases (71 vs. 66 years, p<0.01).
Conclusion
The proportion of durvalumab-associated AE cases reporting pneumonitis was greater for NSCLC vs. other tumor types and increased with age but was not associated with higher deaths or hospitalizations. Pneumonitis constituted a lesser proportion of total AEs in this real-world cohort compared to the PACIFIC trial. Limitations of this retrospective analysis include the potential for under-reporting of AEs to the FAERS database, the inability to establish causality, and the lack of a true denominator. Despite the limitations, these AE findings from a real-world dataset complement clinical trial safety data and support further investigation of interaction of chemoradiotherapy with checkpoint inhibitors in the pathogenesis of pneumonitis.
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P86 - Targeted Therapy - Clinically Focused - New Target (ID 263)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P86.11 - A Real-World Feasibility Study of Patients with Solid Tumors Harboring NRG1 Gene Fusions: NSCLC Subset Analysis (ID 3370)
00:00 - 00:00 | Presenting Author(s): Ajeet Gajra
- Abstract
Introduction
Durable responses to afatinib have been achieved in patients with solid tumors harboring NRG1 gene fusions, including NSCLC, in case reports. Key objectives of this feasibility assessment were to determine the number of patients with NRG1 gene fusion-positive solid tumors available for analyses, characterize their treatment with afatinib/other systemic therapies, and gain insights into treatment patterns and testing for a larger, retrospective, real-world data study. Here, we report a subgroup analysis of patients with NSCLC, the most common primary diagnosis in this feasibility assessment. Some NSCLC subgroup data will be presented at IASLC-NACLC; further updates will be presented at WCLC.
Methods
US physicians in the Cardinal Health Oncology Provider Extended Network retrospectively abstracted data from medical records of adult patients with NRG1 gene fusion-positive solid tumors who had received ≥1 line of systemic therapy (Jan 2017-Mar 2020), and had been followed up for ≥8 weeks. Patients were grouped according to whether they received afatinib (any line), or only received other systemic therapies. Subgroup analysis was conducted for patients with NSCLC primary tumor type. Data were reviewed by Cardinal Health and summarized using descriptive statistics.
Results
Of 107 patients with NRG1 gene fusion-positive solid tumors identified by 12 physicians (n=9 from community practices; n=3 from academic settings), 49 patients (46%) had NSCLC. Of these patients, 26 had received afatinib and 23 received other therapies only (platinum-based therapies ± immunotherapy ± bevacizumab) in any treatment line. Patient characteristics and treatment patterns are reported in the table. NRG1 gene fusion detection methodologies were: mRNA sequencing (n=21; 43%); DNA sequencing (n=14; 29%); unknown (n=14; 29%). Testing was conducted most frequently prior to 1st-line therapy (n=34; 69%). The most common fusion partners were CD74 (n=12; 24.5%) and SCD4 (n=9; 18%); fusion partners were unknown for 14 (29%) patients.
Afatinib (N=26) Other (N=23)* Median age, years 61 (44–79) 63 (38–80) Line in which afatinib/other treatment was received†, n (%) 1 4 (15%) 23 (100%) 2 17 (65%) 8 (35%) 3 5 (19%) 2 (9%) 4 1 (4%) 0 Patients still receiving active therapy‡, n (%) 16 (62%) 8 (35%) Reasons for afatinib/other treatment discontinuation per line in which treatment was received§ (n≥1 in either group), n (%¶) 1st line Disease progression 2 (50%) 3 (13%) Scheduled duration of therapy completed 1 (25%) 9 (39%) Patient died 0 1 (4%) Patient request 0 1 (4%) Unknown 0 5 (22%) 2nd line Disease progression 2 (12%) 2 (25%) Toxicity/adverse event 2 (12%) 1 (13%) Financial challenges 1 (6%) 0 Patient request 1 (6%) 0 Unknown 1 (6%) 5 (63%) 3rd line Disease progression 1 (20%) 0 Toxicity/adverse event 0 1 (50%) Unknown 4 (80%) 1 (50%) *Most common other therapies in 1st line included: cisplatin/pemetrexed ± bevacizumab (n=4), carboplatin/paclitaxel (n=5), and pembrolizumab/cisplatin/paclitaxel or Nab-paclitaxel (n=4); in 2nd line included: pembrolizumab (n=6); in 3rd line included: erlotinib (n=1), and paclitaxel (n=1). †One patient received afatinib monotherapy in 3rd line and afatinib in combination with chemotherapy in 4th line; this patient appears twice here. ‡Eleven patients were still on afatinib at time of data collection, and 5 patients who received afatinib were on other (n=1) or unknown regimens (n=4) at time of data collection. §Disposition of patient who received 4th-line treatment is unknown. ¶Percentage based on number of patients who received therapy per treatment line.
Conclusion
These data support previous findings that NRG1 gene fusions are detected in NSCLC, with almost half of patients in the feasibility assessment having NSCLC primary tumor type. Taken together, these findings provide a rationale to perform a larger, retrospective, chart-based cohort study assessing treatment outcomes in patients with NRG1-positive solid tumors. It is anticipated that further study will provide additional insights into treatment outcomes in NSCLC, the most common primary diagnosis in this assessment.
