Author of

• 11692

  +

  P2.10 - Poster Session 2 - Chemotherapy (ID 207)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11701

    +

    P2.10-009 - Intrinsic and acquired resistance patterns in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy (ID 853)

    09:30 - 09:30  |  Author(s): D.J. Stewart
    • Abstract

    Background
    Platinum-based chemotherapy (PBC) yields clinical benefit in some but not all patients with advanced NSCLC. All patients eventually become resistant to treatment. We assessed degree and timing of onset of tumor regression (TR) and tumor growth (TG) as a surrogate indicator of sensitivity and resistance patterns.

    Methods
    In 130 NSCLC patients on PBC, we assessed percent change in tumor diameter (TG or maximum TR on treatment) compared to pre PBC, and also assessed incremental percent further TR or TG in serial scans compared to the most recent prior scan on treatment.

    Results
    Of the 130 patients, 32 (25%) had intrinsic resistance, with TG at 1[st] repeat scan after 2 cycles of PBC. Only 1 patient with initial TG had later TR on PBC. Among those with TR at 1[st] re-evaluation, pattern of onset of acquired resistance varied: 81 had a 2[nd] repeat scan after 4 cycles of PBC, of whom 20 (25%) had TG. Of 41 patients with earlier TR who then had a 3[rd] repeat scan <4 weeks post PBC cycle 6, 13 (32%) had TG compared to prior scans. In 76% of those with TR, the greatest TR compared to most recent prior scan was seen at the first re-evaluation, with TG or a lower percent TR on later scans. 26 patients had progressive further TR over each of >4 re-evaluation scans, of whom 11 had initial rapid TR at 1[st] re-evaluation, with subsequent more gradual further TR over later scans (a pattern that we designated as “Incremental TR pattern 1”). The other 15 patients with progressive TR over >4 re-evaluation scans had modest initial TR followed by greater TR on a later scan (a pattern that we designated as “Incremental TR pattern 2”). By Spearman coefficients, maximum percent TR from pre PBC (with TG coded as a negative value for TR) correlated with OS (r=0.46, p<0.0001), time to progression (TTP) (r=0.69, p<0.0001) and post-progression survival (PPS) (r=0.30, p=0.001). OS also correlated with TTP (r=0.63, p<0.0001), and PPS correlated with TTP (r=0.44, p<0.0001), and with OS (r=0.95, p<0.0001). Median OS was 11.0 months, and varied with TR pattern (p<0.0001): for patients with first TG at 1[st], 2[nd], 3[rd] and 4[th] repeat scans, median OS was 5.9, 10.8, 10.5 and 15.1 months, respectively. Median OS was 18.2 months in patients with “Incremental TR pattern 1”, and was 30.5 months in patients with “Incremental TR pattern 2”. Median OS with RECIST partial response (23% of patients), minor TR (52%), minor TG (13%) and RECIST progressive disease (13%) was 16.9, 12.4, 9.8 and 4.0 months, respectively (p<0.0001).

    Conclusion
    Intrinsic resistance was noted in 25% of patients. Degree of TR vs TG and patterns of intrinsic and acquired resistance correlated strongly with OS, TTP and PPS, with longest median OS in patients with “Incremental TR pattern 2”. Our observations require confirmation. While numerous biological factors correlate with resistance preclinically, it remains unclear which are most relevant clinically, and it is also unclear what factors may be responsible for the different patterns of clinical resistance observed.