Author of

• 25802

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  OA06 - Early Stage Lung Cancer: Outcomes and Interventions (ID 902)

  • Event: WCLC 2018
  • Type: Oral Abstract Session
  • Track: Treatment of Early Stage/Localized Disease
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 13:30 - 15:00, Room 202 BD

  • 25803

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    OA06.01 - Case-Series Study in Ever- and Never-Smoking Females and Males with NSCLC: Exposures, Tumor Factors, Biology and Survival (SWOG S0424) (ID 14526)

    13:30 - 13:40  |  Author(s): Mary Reid
    • Abstract
    • Presentation
    • Slides

    Background
    Sex differences in non-small cell lung cancer (NSCLC) susceptibility, tumor biology and survival have been retrospectively reported. We conducted a prospective, case-series intergroup study (SWOG S0424) in 4 cohorts of females (F) and males (M), ever-smokers (ES) and never-smokers (NS) with newly-diagnosed stages I-III NSCLC. This is the first overall survival (OS) report. a9ded1e5ce5d75814730bb4caaf49419 Method
    Patients were accrued at US sites via SWOG/NCI-CTSU. A questionnaire of demographics and exposures (tobacco, environmental, reproductive, hormonal); stage and histology data; treatment; and OS were obtained. Tumor tissue was submitted for EGFR, RAS and p53 mutations. Nuclear and cytoplasmic estrogen receptor (ER) alpha and beta were measured (Cheng, JNCI 2017). Kaplan-Meier (KM) curves and OS modeled using Cox proportional hazards were examined. The NS cohorts remained open longer to maximize accrual. Patients were followed 5 years for OS or until death. 4c3880bb027f159e801041b1021e88e8 Result
    The accrual goal of 981 was achieved from 10/2005-3/2011. Evaluable cases were FES, n=337; MES, 383; FNS, 188; MNS, 49 (MNS under-accrued despite extension). The 4 cohorts differed significantly in demographics, tumor stage, histology, mutational profile (overall, by histology), ER expression, lifestyle factors and exposures. KM curves showed MNS/MES had overlapping OS and FNS/FES had significantly better OS. Five-year estimates were FNS, 73%; FES, 69%; MNS, 58%; MES, 52%. Markedly improved OS for females persisted after adjusting for other factors. Four multivariate OS models were constructed: all patients (model 1) and women only (model 2), each with mutations and ER expression added (models 3, 4). Model 1: better OS for females (HR 0.56, p <.001); higher BMI (continuous, HR 0.98, p=0.045); and adenocarcinoma, BAC, large cell (all vs squamous, HRs 0.84, 0.48, 0.57); worse OS for stages II and III (HRs 1.87, 3.76: each p<.001) and greater age. Model 2: worse OS if ES (HR 1.48, p=0.05), higher stages; histology and hormonal exposure variables were not significant. Model 3: better OS if EGFR mutation (HR 0.53, p=0.013), female, stage I, higher BMI or greater height; worse OS if p53 mutation, higher ER-alpha cytoplasmic or ER-beta nuclear H-scores. Model 4: worse OS if higher stage, p53 mutation or ER-alpha cytoplasmic H-score; EGFR mutation lost significance. 8eea62084ca7e541d918e823422bd82e Conclusion
    Sex, histology, mutations and exposures impacted OS, with dramatically better OS for females regardless of the analysis/model. Hormonal influences (persistent association of ER-expression with OS) were independently significant. Despite adjustments, favorable female survival could not be explained away. Randomized studies should stratify by sex and validation analyses should be conducted in targeted therapy and immunotherapy trials.
    
    SUPPORT: NIH/NCI grants R01CA106815, U10CA180888, U10CA180819 and UG1CA189974. 6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25941

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  P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27003

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    P2.04-26 - Interim Results from a Phase I/II Trial of Nivolumab in Combination with CIMAvax-EGF as Second-Line Therapy in Advanced NSCLC (ID 13359)

    16:45 - 18:00  |  Author(s): Mary Reid
    • Abstract

    Background
    

    CIMAvax-EGF (CE), a recombinant anti-human epidermal growth factor (EGF) vaccine, has demonstrated survival benefit as maintenance therapy in advanced NSCLC. We report the results from the dose-escalation phase I portion of the study investigating CE in combination with Nivolumab(N) in patients (pts) with advanced stage, previously treated immunotherapy-naïve NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This is an open-label phase I dose-escalation study with a 3+3 design. Intramuscular CE is investigated in two dose levels (1.2 and 2.4 mg, given q 2 weeks x 4 doses during the induction phase, then q monthly during the maintenance phase) in combination with 240 mg iv N q 2 weeks. Pts remain on treatment until disease progression, serious toxicity or consent withdrawal. The primary objective is to determine the safety and recommended phase II dose (RP2D) of CE in combination with N. Secondary objectives include tumor response and correlative markers of immune response. Toxicities are graded according to CTCAE v4.03. No intra-pt dose escalation is allowed

    4c3880bb027f159e801041b1021e88e8 Result
    

    9 pts have completed DLT assessments (7Female: 2Male). Median age is 58 (range 46-69). All pts have EGFR, KRAS and ALK wildtype NSCLC. Adenocarcinoma is the predominant histologic subtype (7/9). One pt had Gr 3 myocarditis (LVEF 25%-30%) attributed to N alone on Cycle 1 day 8 and taken off study. LVEF improved (60%-65%) but pt eventually had Gr 5 brain hemorrhage due to brain metastasis, unrelated to treatment, on Cycle 1 day 29. No other treatment-related CTC grade 3+ AEs attributed to either N and/or CE. The RP2D dose was established at 2.4 mg for CE. Objective response rate of 44% was seen (4 PRs: 3 adenocarcinoma, 1 squamous; 3 PD-L1 <1%, 1 PD-L1 60%). There is a significant inverse correlation (p<0.001) between the temporal change in anti-EGF Ab titers and the change in serum EGF levels based upon a generalized linear model. 71% of pts (95% CI 36%-92%) achieved an anti-EGF Ab titer of > 1:4000 after 3 vaccine doses by day 43. We will present additional information on safety, efficacy profile and correlative data in the meeting

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Combination of N+CE did not show unexpected toxicities. Preliminary efficacy and immunological data warrant further investigation.

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