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Julian R. Molina



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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
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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): Julian R. Molina

      • 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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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-17 - Immune-Related Adverse Events in Patients with Metastatic Non-Small Cell Lung Cancer: Sex Differences and Response to Therapy. (ID 12642)

      16:45 - 18:00  |  Author(s): Julian R. Molina

      • Abstract
      • Slides

      Background

      Sex differences in non-small cell lung cancer (NSCLC) outcomes have been described. Immune-related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors (ICI). Risk factors for IRAEs and their association with response to therapy remain controversial. Therefore, we studied sex differences in IRAEs and their association with response to therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients with metastatic NSCLC treated with anti-PD1 and anti-PDL1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Patients receiving treatment at an outside facility or with history autoimmune disorders were excluded. Kaplan-Meier method was used for time-to-event analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      231 patients were identified, 120 (52%) were women and 111 (48%) were men. Baseline characteristics and ICI distribution were similar among groups (Table 1). Women were more likely to experience IRAEs compared to men (48% vs. 31%, p<0.008). Among patients with IRAEs, women were more likely to be prescribed systemic steroids (63% vs. 41%, p<0.02). Women were more likely to develop pneumonitis (23% vs. 12%, p<0.03) and arthralgia (17% vs. 3%, p<0.04). However, dermatologic toxicities (35% vs. 9%, p<0.002) were more commonly seen in men. In 17% of women the ICI was discontinued due to toxicity (men 7%). Besides sex, no other clinical characteristic was associated with increased IRAEs. Women with IRAEs were more likely to have a radiographic response compared with women without IRAEs (78% vs. 23%, p<0.0001), although this was not observed in men (37% vs. 26%, p>0.22). Better PFS was observed in women with IRAEs (10 months vs. 3.3 months, p<0.0006) compared to women without IRAEs.

      Women % (n)

      Men % (n)

      p value

      PD-L1 expression ≥1%

      30 (36)

      34 (38)

      0.29

      Adenocarcinoma

      77 (92)

      66 (73)

      0.02

      Bone metastasis

      34 (41)

      47 (52)

      0.05

      Brain metastasis

      20 (24)

      22 (24)

      0.76

      Liver metastasis

      13 (15)

      10 (11)

      0.53

      Prior chemotherapy

      74 (89)

      85 (94)

      0.06

      Prior palliative radiation

      53 (63)

      57 (63)

      0.52

      IRAEs

      48 (57)

      31 (34)

      0.006

      ≥3 grade IRAEs

      42 (24)

      29 (10)

      0.22

      Received systemic steroids

      63 (36)

      41 (14)

      0.02

      Required intravenous steroids

      30 (17)

      24 (8)

      0.47

      8eea62084ca7e541d918e823422bd82e Conclusion

      Women with metastatic NSCLC are more likely to experience IRAEs compared to men. In women, an association between IRAEs and response to therapy was observed. Larger studies are needed to investigate the mechanisms underlying these associations.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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