Virtual Library

Start Your Search

I. Pastan



Author of

  • +

    O22 - Mesothelioma III (ID 122)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
    • +

      O22.03 - Durable cancer regressions in chemotherapy refractory mesothelioma patients with the anti-mesothelin immunotoxin SS1P and host immune depletion with pentostatin (P) and cyclophosphamide (C) (ID 1630)

      16:35 - 16:45  |  Author(s): I. Pastan

      • Abstract
      • Slides

      Background
      SS1P is a recombinant immunotoxin targeting the tumor differentiation antigen mesothelin, which is highly expressed in mesothelioma. Anti-tumor activity of SS1P was limited in phase I clinical trials due to development of neutralizing antibodies (NAbs) that limited treatment to one cycle. In immunocompetent mice P and C (P-C) can abrogate development of anti-SS1P NAbs. This pilot study was performed to determine the impact of P-C-based immune depletion on anti-SS1P NAb formation and to assess safety of P-C-SS1P.

      Methods
      Patients with progressive pleural or peritoneal mesothelioma who previously received platinum-based therapy were eligible. Up to 6 cycles of P 4 mg/m2 IV (cycle 1: days 1, 5, 9; cycle 2-6: day 1); C 200 mg PO (cycle 1: days 1-12; cycle 2-6: days 1-4) and SS1P IV (35 µg/kg, cycle 1: days 10, 12, 14; cycle 2-6: days 2, 4, 6) were administered (cycle 1 was 30 days and cycles 2-6 were 21 days) with restaging every 2 cycles in the absence of progressive disease and anti-SS1P NAbs.

      Results
      Eleven patients were enrolled. The median age was 52 years (range 43-68); male 7, female 4; pleural 9, peritoneal 2; median number of prior treatments was 3 (range 2-6). Three out of 10 evaluable patients had partial response with tumor regressions of 74%, 70% and 44% with complete resolution of metabolic activity in two patients and >70% reduction in the third (Table). The overall survival of these patients is 17+, 15+ and 18+ months. In addition, one patient with stable disease and one patient with progressive disease had dramatic response to post-SS1P chemotherapy using drugs to which they had not responded previously. All five patients who responded are alive with overall survival ranging from 11 to 18 months. The regimen of P-C delayed development of NAbs to SS1P, thereby allowing multiple cycles of therapy with SS1P. Only 2 of 10 (20%) patients developed anti-SS1P NAbs after one cycle compared to 88% of patients who received single agent SS1P in a previous study (p=0.0001), thus meeting the primary endpoint. The regimen of P-C-SS1P was safe and well tolerated and no patient developed opportunistic infections. Grade ≥ 3 adverse events were P-C related lymphopenia (100%), transaminitis (18%) and SS1P related back pain (9%), non-cardiac chest pain (18%) and fever (9%).

      Pt Overall Tumor Response[†] Delayed Tumor Response[§] Post Study Chemo. Response to Post-SS1P Chemo. Overall Survival (months)
      1 PR (-44%) Yes (7 m+) - - 18.2+
      2 PR (-74%) - - - 17.1+
      3 SD - Yes PR (-55%)* 15+
      4 PR (-70%) - - - 14.5+
      5 SD - - - 8.8
      6 PD - - - 6.2
      7 PD - - - 5.7
      8 PD Yes (4 m+)** Yes 85% decrease in tumor [18]F-FDG uptake[¶] 10.6+
      9 PD - - - 4.2
      10 SD - Yes No 7.3
      PR, partial response; SD, stable disease; PD, progressive disease; [18]F-FDG, Fluorodeoxyglucose; [†]In patients with tumor response the maximum percent decrease in tumor dimensions is shown; [§]Months from study initiation when response first observed; * PR to post-SS1P treatment with previously ineffective chemotherapy; **Patient 8 had initial PD, but at 4 months had 25% reduction in size of one of the target lesions and marked decrease of metabolic activity by PET; [¶]Patient 8 had 85% reduction in metabolic activity compared to baseline and SD by CT scan on post- SS1P chemotherapy.

      Conclusion
      SS1P and immune depletion with P-C results in significant and durable anti-tumor activity in heavily pre-treated chemotherapy refractory patients with mesothelioma.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.