Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

M. Gandhi



Author of

  • +

    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      P2.03a-044 - Severe Adverse Events Impact Overall Survival (OS) and Costs in Elderly Patients with Advanced NSCLC on Second-Line Therapy (ID 5064)

      14:30 - 14:30  |  Author(s): M. Gandhi

      • Abstract

      Background:
      Among elderly patients with advanced non-small cell lung cancer (aNSCLC), treatment beyond first-line therapy may be associated with higher risk of adverse events (AEs) due to patients’ poorer performance status and higher disease burden and comorbidities. This study assessed the impact of severe AEs during second-line (2L) therapy on OS and cost of care in elderly with aNSCLC.

      Methods:
      Patients aged ≥65 years, diagnosed with aNSCLC between 2007-2011 and receiving 2L chemotherapy/targeted therapy, were identified in the SEER-Medicare database (2006-2013). 57 AEs were identified by literature review and consultation with an oncologist. Severe AEs were operationalized as hospitalizations during which a diagnosis for ≥1 AEs was recorded. OS and all-cause healthcare costs post-initiation of 2L chemotherapy/targeted therapy were compared between patients with and without severe AEs.

      Results:
      Among 3967 patients initiating 2L, 1624 (41%) had ≥1 severe AEs where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs were similar in demographic and cancer characteristics at diagnosis and 2L treatment regimens; although patients with severe AEs had more comorbidities, notably anemia (69% vs 60%). Median OS for patients with severe AEs was almost half of that for patients without severe AEs (6 vs 11 months). After adjustment for potential confounders, patients with severe AEs had more than double risk of death than patients without severe AEs. Cost of caring for patients with severe AEs was more than twice higher than those patients without severe AEs ($16,135 vs $7,559 per-patient-per-month).

      OS With severe AEs cohort N = 1,624 Without severe AEs cohort N = 2,343
      Kaplan-Meier rates (95% CI)
      1 year post 2L initiation 26% (24 - 28) 46% (44 - 48)
      2 years post 2L initiation 11% (9-13) 23% (21-25)
      Median survival time (in months) 6 11
      Adjusted hazard ratio[1] (95% CI) 2.31 (2.16 - 2.47)
      [1] Patients with vs without severe AEs
      AE: adverse event; 2L: second line chemotherapy/targeted therapy; CI: confidence intervals


      Conclusion:
      Occurrence of severe AEs among elderly aNSCLC patients who are receiving 2L chemotherapy/targeted therapy is associated with worse clinical outcomes and a higher economic burden. Results of this analysis suggest that better tolerated therapies may improve outcomes for patients and reduce cost to the healthcare system.

  • +

    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      P2.03b-014 - Atezolizumab in Advanced NSCLC Patients with Baseline Brain Metastases: A Pooled Cohort Safety Analysis (ID 5214)

      14:30 - 14:30  |  Author(s): M. Gandhi

      • Abstract

      Background:
      Brain metastases, occurring in 20% to 40% of patients with advanced NSCLC, are associated with poor survival. Atezolizumab (anti-PDL1) inhibits PD-L1/PD-1 signaling and restores tumor-specific T-cell immunity. Clinical benefits have been observed in patients with NSCLC across PD-L1 expression levels following atezolizumab monotherapy, but the safety profile in NSCLC patients with brain metastases has not previously been explored.

      Methods:
      Pooled safety analyses were conducted in 843 patients who received atezolizumab as 2L+ treatment in 4 studies (PCD4989g: NCT01375842 [N = 76]; BIRCH: NCT02031458 [N = 520]; FIR: NCT01846416 [N = 105]; POPLAR: NCT01903993 [N = 142]). Patients had asymptomatic untreated brain metastases or stable previously treated brain metastases at baseline.

      Results:
      27 (3%) of 843 patients in the pooled cohort had baseline brain metastases; 23 of whom were previously treated with radiation to the brain. Among the 27 patients, mean age was 60 years, 41% were male, 85% had non-squamous NSCLC, and 70% had received 3L+ therapy. Median number of atezolizumab cycles (21d/cycle) was 4 (range, 1-39). Neurological AEs occurred in 12 (44%) patients with and 229 (28%) patients without baseline brain metastases (Table). The incidence of treatment-related neurological AEs was 4 (15%) in patients with and 77 (9%) in patients without baseline brain metastases, including the most common treatment-related AE of headache in 2 (7%) and 27 (3%) patients, respectively. The most common all-cause AEs in patients with baseline brain metastases were fatigue, nausea, and vomiting (7 [26%] each); 3 (11%) patients developed new brain lesions on study, none during treatment. No treatment discontinuations occurred due to AEs.

      Conclusion:
      The current analyses indicate that atezolizumab has an acceptable safety profile in patients with NSCLC who have asymptomatic or previously treated stable brain metastases. Further investigation is needed to fully assess the efficacy of atezolizumab in this patient population.

      Summary of safety data in patients with advanced NSCLC with and without baseline brain metastases following atezolizumab as 2L+ treatment
      Pooled Cohort (N = 843)
      Patients Without Baseline Brain Metastases (n = 816) n (%) Patients With Baseline Brain Metastases (n = 27) n (%)
      Any AE 779 (96%) 26 (96%)
      Any neurological AE 229 (28%) 12 (44%)
      Treatment-related AEs 548 (67%) 16 (59%)
      Treatment-related neurological AEs 77 (9%) 4 (15%)
      Serious AE 311 (38%) 9 (33%)
      Serious neurological AEs 21 (3%) 1 (4%)
      Treatment-related SAEs 78 (10%) 1 (4%)
      Discontinued treatment due to AE 47 (6%) 0 (0%)


  • +

    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
    • +

      P2.06-019 - A Phase II Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients (pts) with Resectable Non-Small Cell Lung Cancer (NSCLC) (ID 4642)

      14:30 - 14:30  |  Author(s): M. Gandhi

      • Abstract

      Background:
      There is no curative treatment for patients with NSCLC who develop metastatic disease after resection. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated an absolute survival benefit of 5% for patients with stages IB, II, and IIIA disease. Clearly, developing new treatment strategies to improve survival following resection is critical to improving outcomes for this patient population. Immunotherapy with checkpoint inhibitors such as antibodies to PD-1 and PD-L1 has demonstrated superior survival compared to chemotherapy in randomized clinical trials. PD-L1 expression is being investigated as a predictive biomarker for these therapies, but its ability to predict response has varied in published trials. Atezolizumab is a humanized IgG1 monoclonal PD-L1 antibody that was recently evaluated in the POPLAR trial (NCT01903993), a phase II randomized trial of patients with NSCLC who progressed on platinum based chemotherapy. Atezolizumab therapy improved overall survival compared with docetaxel (12.6 months vs. 9.7 months, HR 0.73 [95% CI 0.53 – 0.99]) with a manageable safety profile. Improvement in survival correlated with PD-L1 immunohistochemistry expression of tumor and tumor-infiltrating immune cells.

      Methods:
      Trial design: This phase II, open-label, single-arm study is designed to evaluate the efficacy and safety of atezolizumab as a neoadjuvant therapy in patients with Stage IB, II, or IIIA NSCLC prior to curative-intent resection. Approximately 180 patients with NSCLC will be enrolled in this study at 15 academic medical centers in the United States. There are two parts to this study: the first/primary part will evaluate the ability of neoadjuvant atezolizumab to produce objective pathologic responses in patients with early stage NSCLC. Atezolizumab 1200 mg IV will be given every 3 weeks for two doses. Surgical resection of tumors following treatment will allow determination of pathologic response rates and potential predictive biomarkers. Part 2 is exploratory and will evaluate atezolizumab adjuvant therapy for up to 12 months in patients who demonstrate clinical benefit (evidence of pathologic response or absence of radiographic progression) in Part 1. After surgical resection, patients may receive SOC adjuvant chemotherapy (with or without radiation) before starting atezolizumab adjuvant therapy in Part 2. The primary objectives are safety and major pathologic response based on surgical resection. Secondary objectives include overall response rate based on PD-L1 status, mutational load, antigen burden, and RNA-sequencing. This trial presents a unique opportunity to evaluate exploratory biomarkers, including pre- and post-treatment biopsy assessment of evolution of immune related markers associated with response.

      Results:
      Section not applicable

      Conclusion:
      Section not applicable