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Nagashree Seetharamu



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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-26 - Impact of Concurrent Tumor Suppressor Gene Mutation on Clinical Outcomes in EGFR Mutated NSCLC Treated with First-Line TKI (ID 13595)

      16:45 - 18:00  |  Author(s): Nagashree Seetharamu

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor (EGFR) mutations confer good prognosis in non-small cell lung cancer (NSCLC) and a multitude of tyrosine kinase inhibitors (TKI) are currently available for treatment of these tumors. However, development of resistance to these drugs is imminent and remains a challenging clinical conundrum. Few studies have demonstrated the presence of concurrent tumor protein 53 (TP53) mutation to result in earlier resistance to TKI. We conducted a retrospective study to determine whether or not TP53 or other tumor suppressive gene mutations impacted clinical outcomes in EGFR mutated NSCLC. Progression free survival (PFS) and disease control rate (DCR) as defined by complete response (CR), partial response (PR) or stable disease (SD) were assessed.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with EGFR mutated NSCLC treated with first-line TKI at our institution from January 2014 to June 2017 were included. Patients were dichotomized based on presence or absence of TP53 mutation. Comparisons were also made between patients with and without any tumor suppressor gene mutations. Descriptive statistics was used to summarize the data. Two sample t-test assuming unequal variance was used to compare mean PFS between groups and chi-square test to compare proportions.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 44 patients, 72.7% had exon 19 deletions and 27.3% had exon 21 L858R point mutation. 54.5% patients had a concomitant tumor suppressor gene mutation with TP53 being the most common gene mutated (47.7%). 45.4% patients had no concurrent mutations. Comparative results is shown in Table 1.wclc.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Mean and median PFS were longer in patients without concomitant tumor suppressive gene mutations. Though statistically not significant likely due to lack of power, these results are provocative. This should be explored further in a larger patient population and future clinical trials with EGFR TKI stratifying patients based on concomitant tumor suppressor gene mutations.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P2.13-38 - Impact of Tyrosine Kinase Inhibitor (TKI) Dose on Outcomes of Patients with Lung Cancer (ID 11770)

      16:45 - 18:00  |  Author(s): Nagashree Seetharamu

      • Abstract
      • Slides

      Background

      FDA approved starting doses of TKis are based on maximum tolerated dose (MTD) in clinical trials. In practice however, patients are started on lower doses due to tolerability concerns or dose-reduced subsequently for toxicity. Very few studies have addressed the impact of dose on clinical outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      An IRB approved chart review of lung cancer patients receiving oral TKI therapy between 1/2014 and 6/2017 at our institution was conducted. Patients who were started on TKIs at the FDA dose (Group A) dose were compared to those started on a lower dose (Group B) for progression free survival (PFS), overall survival (OS), and time-to-discontinuation. Fisher’s exact test was used to compare groups on categorical variables and the Mann-Whitney test was used for continuous variables. The Kaplan-Meier method was used to estimate time-to-event stratified by group, and Cox regression models were used to adjust for potential confounders.

      4c3880bb027f159e801041b1021e88e8 Result

      Seventy-nine patients were treated with an EGFR inhibitor and 11 patients were treated an ALK inhibitor. The Kaplan-Meier estimates of the median time-to-progression for Group A (n = 67) and Group B (n = 23) were 13.4 months (95% CI: 8.88, 15.55) and 15.1 months (95% CI: 5.56, 21.5), respectively; and for time-to-discontinuation, the estimates were 13.5 months (95% CI: 11, 20.15) for Group A and 21.5 months (95% CI: 6.44, ) for Group B. Median time to death was not estimable for OS. The predicted OS probability at approximately 15 months post treatment initiation for Group A was 81.8% (95% CI: 0.69, 0.90) vs. 80.5% (95% CI: 0.55, 0.92) for Group B. No statistically significant differences resulted from the Cox regression models.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We found no evidence to support that patients who initiated therapy at full dose have different outcomes with respect to OS and PFS compared to those who initiated at a lower starting dose. Future prospective studies are needed to further evaluate this finding. Future clinical trials should report minimal effective dose in addition to MTD.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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