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Janakiraman Subramanian



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    MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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      MA15.11 - Real World Biomarker Testing and Treatment Patterns in Patients with Advanced NSCLC Receiving EGFR-TKIs (ID 12705)

      14:40 - 14:45  |  Author(s): Janakiraman Subramanian

      • Abstract
      • Presentation
      • Slides

      Background

      In patients who progress on treatment with first- or second-generation EGFR-TKIs, 50–60% will have an EGFR T790M resistance mutation. Osimertinib, a third-generation EGFR-TKI, is FDA approved for use in patients with metastatic EGFR T790M-positive NSCLC and disease progression on or after prior EGFR-TKI therapy, and recently gained additional approval for first-line treatment for patients with EGFR Ex19del/L858R positive advanced NSCLC. We sought to observe how many patients in the real world underwent biomarker testing on progression and subsequently received osimertinib, when T790M positive.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Flatiron Health EHR-derived database was used to identify adult patients with NSCLC treated with a first- or second-generation EGFR-TKI from 11/2015–09/2017, with the start of first EGFR-TKI defined as the index date. Patients were stratified by EGFR-TKI use as a first (1L) or later line (2L+) treatment. EGFRm status, including T790M testing and subsequent treatments received after initiating first- or second-generation EGFR-TKI, were described. Chart review was conducted on patients who received a subsequent therapy to confirm disease progression.

      4c3880bb027f159e801041b1021e88e8 Result

      Patients in this study (n=782; 1L: n=435; 2L+: n=347) had a median age of 69 years, 64% were female, 56% were white, 87% were seen in the community, with a median follow-up of 307 days. During the study period, 30% (235/782; 1L: 96/435 [22%]; 2L+: 139/347 [40%]) of patients died without receiving a subsequent therapy, and 38% (294/782; 1L: 160/435 [37%]; 2L+: 134/347 [39%]) received subsequent therapies. From post-index date to initiation of subsequent therapies, 30% (88/294; 1L 63/160 [39%]; 2L+ 25/134 [19%]) of patients were tested for EGFR mutations including T790M. Among patients who received subsequent therapies, treatments included chemotherapies (1L=23%; 2L+=37%), immunotherapies (1L=16%; 2L+=43%), and targeted therapies (1L=64%; 2L+=30%). On progression, 25% (1L 40/160) and 5% (2L+ 7/134) of the patients received osimertinib. Of those tested for EGFR mutation post-index date (n=88), 28% (n=25) were positive for T790M and 96% of these (n=24) received osimertinib. Most patients (251/294 [85%]; 1L: 136/160 [85%]; 2L+: 115/134 [86%]) on subsequent therapies were confirmed to have disease progression at chart review.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this study, a third of patients were tested for subsequent EGFR mutations including EGFR T790M following treatment with first- or second-generation EGFR-TKI. Of these, a third were positive for T790M and nearly all of the T790M positive patients received osimertinib. These findings highlight low rates of biomarker testing at progression, and the need for optimal treatments that maximize benefits for patients with EGFRm NSCLC.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-60 - Clinical Utility of Circulating Tumor Cell (CTC) Analysis Using Target Selector™ in Metastatic NSCLC Chemotherapy Patients (ID 14290)

      16:45 - 18:00  |  Author(s): Janakiraman Subramanian

      • Abstract
      • Slides

      Background

      Over half of lung cancer patients present with advanced stage disease at diagnosis. Liquid biopsy is emerging as a minimally invasive and cost-effective means of cancer biomarker evaluation to select appropriate treatment and monitor disease burden. CTC enumeration may have prognostic and predictive potential for patients receiving chemotherapy. Here we describe interim results of a prospective study analyzing blood CTCs from treatment-naïve patients with histologically confirmed metastatic non-small cell lung cancer (NSCLC) who are candidates for systemic cytotoxic chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Venous blood samples were obtained for CTC analysis before administration of chemotherapy on treatment days (D) 1, 8, 22 and 43, and at disease progression. Blood was collected in Biocept CEE-Sure™ blood collection tubes, and samples were processed at Biocept's CLIA-certified, CAP-accredited laboratory. Biocept’s Target Selector™ CTC platform uses an antibody capture cocktail and microfluidic channel for CTC capture and biomarker analysis. Study objectives include determining the proportion of patients with D1 CTC detection, and CTC correlation to time to progression and overall survival (OS).

      4c3880bb027f159e801041b1021e88e8 Result

      Twenty-three patients have been enrolled so far in this ongoing study: 16 (69.5%) adenocarcinoma, 7 (30.4%) squamous cell carcinoma. Fifteen patients progressed on initial therapy to date, with a median time to progression of 110 days. Of 22 patients with blood collections at D1 (treatment start), 14 (63.6%; 10 adenocarcinoma, 4 squamous) had detectable CTCs. For patients with detectable D1 CTCs, CTC count at D8 decreased in 13/14 (92.9%; 9 adenocarcinoma, 4 squamous) subjects, and was unchanged in 1 individual (7.1%; adenocarcinoma). Patients with 1-5 CTCs at D1 had a mean time to progression of 140.75 days; patients with >5 CTCs at D1 had a mean time to progression of 101.83 days (p=0.17). Among patients with undetectable CTCs at D1, CTCs remained undetectable in 4/8 (50%; all adenocarcinoma) and increased in 2/8 (25%; one each of adenocarcinoma and squamous) of subjects; CTCs were not collected at D8 for 2 individuals.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Implementation of Biocept’s TargetSelector™ enables the highly sensitive detection of CTCs in the clinical setting. CTCs are detectable in the majority of patients with metastatic NSCLC. In subjects with detectable CTCs prior to chemotherapy, CTC count declines within a week after starting chemotherapy in >90% patients. Preliminary data suggest that CTC enumeration may have prognostic and predictive potential for patients receiving chemotherapy. Further data from this ongoing study may provide additional insight into the role of CTC analysis applied to clinical practice.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.15-26 - Rates and Economic Burden of Adverse Events in Patients With Metastatic NSCLC Treated with EGFR-TKIs (ID 13643)

      16:45 - 18:00  |  Presenting Author(s): Janakiraman Subramanian

      • Abstract
      • Slides

      Background

      Trials of first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have reported severe adverse events (SAEs) in 6%–49% of patients with EGFR-mutant (EGFRm) metastatic non-small cell lung cancer (mNSCLC). This study describes the real-world rates and incremental cost of AEs in this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Adults with mNSCLC treated with EGFR-TKIs as first-line therapy (first dispensing defined as the index date) with ≥1 lung cancer diagnosis code, no claim for a lung surgery, and no administration of other NSCLC therapies during 3 months pre-index date were identified from the IQVIATM Real-World Data Adjudicated Claims – US database (Q2/2012–Q1/2017). The select AEs identified from prescribing information of EGFR-TKIs were skin and ocular disorders, interstitial lung disease (ILD), diarrhea, microangiopathic hemolytic anemia, gastrointestinal perforation, cardiac and cerebrovascular events, renal failure, and hepatotoxicity. AE rates per 1,000 patient-years and healthcare cost per-patient-per-month (PPPM) were calculated during first-line therapy. Multivariate linear regression was used to assess cost differences (CD) for patients with and without AEs, adjusting for baseline characteristics. All AEs (outpatient and hospitalization claims) and a subgroup of SAEs (hospitalization claims) were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 1,646 patients, 86.1% were treated with erlotinib, 12.1% with afatinib, and 1.0% with gefitinib. During first-line therapy, 549 patients had ≥1 acute AE (33.4%, 870.9 per 1,000 patient-years) and 200 patients had ≥1 acute SAE (12.2%, 220.1 per 1,000 patient-years). Skin and ocular disorders (17.6%, 482.9 per 1,000 patient-years) and ILD (4.5%, 139.6 per 1,000 patient-years) had the highest rate among all AEs and SAEs, respectively (Figure). Patients with AEs had higher PPPM healthcare costs than patients without AEs (all AEs: CD=$1,079, p<0.001; SAEs: CD=$4,700, p<0.001).

      figue_rate of occurrence of acute aes during treatment period.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Over one-tenth of patients suffered from SAEs, resulting in a sizeable economic burden. EGFR-TKIs with more favorable safety profiles may reduce substantial healthcare costs in this patient population.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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