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J. Pujol



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    P2.08 - Poster Session 2 - Radiotherapy (ID 198)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P2.08-019 - Palliative radiation during pemetrexed plus cisplatin first-line treatment or pemetrexed continuation maintenance treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): A report of patient safety in the PARAMOUNT trial (ID 2364)

      09:30 - 09:30  |  Author(s): J. Pujol

      • Abstract

      Background
      Patient (pt) safety is of utmost concern to radiation oncologists. Pemetrexed (Pem) is an effective and well-tolerated treatment for advanced nonsquamous NSCLC. The safety of palliative radiation (XRT) during Pem treatment was studied in this subset of pts in the PARAMOUNT trial.

      Methods
      In PARAMOUNT, a randomized, double-blind study, 939 pts received 4 cycles of induction Pem (500 mg/m[2]) + cisplatin (Cis) (75 mg/m[2]) on day 1 every 21 days. Patients without progressive disease (PD) and with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1 (n=539) were then randomized (2:1) to maintenance Pem (500 mg/m[2], day 1) + best supportive care (BSC) (Arm A) or placebo + BSC (Arm B) until PD. Best supportive care (BSC) was defined as treatment without a specific antineoplastic regimen and included palliative XRT to extrathoracic structures. Safety was assessed via the incidence of adverse events (AEs) by maximum grade (Gr; CTCAE, v3).

      Results
      The 55 pts who received palliative XRT to extrathoracic structures during treatment had stage IV nonsquamous NSCLC. The majority of pts were male (58%), with an ECOG PS of 1 (75%). Patients’ median age was 61 yrs (range, 32-74) yrs, with 13% of pts ≥70 yrs. The most common location irradiated was bone (43/55 pts). Non-bone locations were: lymph node (3), mediastinum (2), chest (2), and adrenal gland, intraocular, lung, brain, and abdomen (1 each). Forty-five pts received XRT during Pem+Cis induction, 3 of whom also received XRT during maintenance. Seven pts (Arm A) and 6 pts (Arm B) received palliative XRT during maintenance. Total XRT doses ranged from 8-66 Gy. The time interval between day 1 of last chemotherapy cycle and the start of palliative XRT ranged from 0-28 days. Of 55 pts, 12 (22%) had ≥1 AE(s) during XRT considered possibly related to Pem and/or XRT (Table 1). All pts except 1 experienced the AE during induction. The most common AE was Gr 2 anemia. Three pts had Gr 3/4 anemia. Five pts had nonhematologic toxicities. One pt in Arm B, who received a total dose of 20 Gy in the hip during maintenance treatment, had pneumonitis. No AEs were reported for pts who received palliative XRT during Pem maintenance treatment.

      Table 1: AEs during palliative XRT or within 2 weeks after the end of the last fraction in both phases of the PARAMOUNT trial.
      Pts receiving palliative XRT (N=55)
      Patients with AEs during induction and/or maintenance (n=12, 22%)
      Toxicity Gr 1, n (%) Gr 2, n (%) Gr 3-4, n (%)
      Hematologic
      Hemoglobin 1 (1.8) 4 (7.3) 3 (5.5)
      Leukocytes 0 2 (3.6) 1 (1.8)
      Platelets 0 1 (1.8) 0
      Nonhematologic
      Rash/dermatitis 1 (1.8) 1 (1.8) 0
      Rash/desquamation 1 (1.8) 1 (1.8) 0
      Pneumonitis 0 0 1 (1.8)*
      *Pneumonitis was the only event reported for a pt during the maintenance phase. The pt was assigned to placebo.

      Conclusion
      Conclusions: In PARAMOUNT, palliative XRT is well tolerated and can be safely administered at low and high doses during Pem+Cis chemotherapy or Pem monotherapy to pts with advanced nonsquamous NSCLC.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-037 - Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after completing at least 4 cycles of pemetrexed plus cisplatin induction treatment: a cross-trial analysis of two phase III trials (ID 2449)

      09:30 - 09:30  |  Author(s): J. Pujol

      • Abstract

      Background
      In a phase III trial, JMDB, the subgroup of patients with nonsquamous histology showed a significant improvement in survival after treatment with first-line pemetrexed + cisplatin (pem 500 mg/m[2] + cis 75 mg/m[2] every 21 days for a maximum of 6 cycles). In PARAMOUNT, a double-blind, placebo-controlled, phase III trial, 539 patients with advanced nonsquamous NSCLC and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 were randomized to maintenance pem or placebo after completing 4 cycles of pem+cis without disease progression.

      Methods
      We compared patients from the two randomized arms of PARAMOUNT with a selected homogeneous population from JMDB: 346 patients with advanced nonsquamous NSCLC and an ECOG PS of 0 or 1 who completed at least 4 cycles of pem+cis without disease progression. Efficacy outcomes included overall survival (OS) and progression-free survival (PFS) measured from the start of treatment with pem+cis and analyzed by Kaplan-Meier and Cox methods. Rates of toxicities were calculated without formal statistical comparison.

      Results
      Outcomes for the JMDB homogeneous group were similar to the PARAMOUNT placebo arm (PFS: 6.24 vs 5.59, p=0.117; OS: 14.23 vs 13.96, p=0.979). The PARAMOUNT pem group had statistically superior efficacy compared with the JMDB homogeneous group (PFS: 7.46 vs 6.24 p<0.00001; OS: 16.89 vs 14.23 p=0.003). Patients who received pem maintenance displayed numerically higher incidences of drug-related serious adverse events (SAEs) compared with JMDB patients who received ≥4 cycles of pem+cis (10.6% vs 2.9%); grade 3/4 anemia and fatigue were higher in the pem arm of PARAMOUNT. A comparable number of patients (approximately 2/3) on both arms of PARAMOUNT and on JMDB received post-discontinuation systemic therapy (PDT). Results are summarized in Table 1. Table 1: Summary of survival, post-discontinuation systemic therapy , and selected drug-related adverse events in the PARAMOUNT pem and placebo arms and the JMDB homogeneous group

      PARAMOUNT pem arm (n=359) PARAMOUNT placebo arm (n=180) JMDB homogeneous group (n=346)
      PFS
      Median (95% CI), mos 7.46 (6.90-8.57) 5.59 (5.45-5.95) 6.24 (5.91-6.54)
      Cox unadjusted HR (95% CI) 0.66 (0.56-0.77)* 0.86 (0.72-1.04)**
      Unadjusted log-rank p-value <0.00001* 0.117**
      OS
      Median (95% CI), mos 16.89 (15.77-18.99) 13.96 (12.88-15.51) 14.23 (12.94-15.05)
      Cox unadjusted HR (95% CI) 0.75 (0.63-0.91)* 1.00 (0.81-1.24)**
      Unadjusted log-rank p-value 0.003* 0.979**
      Received any PDT, n % 231 (64.3) 129 (71.7) 207 (59.8)
      Patients with ≥1 drug-related SAE, n (%) 38 (10.6) 8 (4.4) 10 (2.9)
      Hematologic grade 3/4 toxicities, n (%)
      Anemia Hemoglobin decreased Hemoglobin 16 (4.5) 2 (0.6) 0 (0.0) 2 (1.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 10 (2.9)
      Neutropenia Neutophils/granulocytes 17 (4.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (5.2)
      Nonhematologic grade 3/4 toxicities, n (%)
      Fatigue 11 (3.1) 2 (1.1) 5 (1.4)
      *PARAMOUNT pem arm vs JMDB homogeneous group; **PARAMOUNT placebo arm vs JMDB homogeneous group. Abbreviations: PDT=post-discontinuation systemic therapy; PFS: progression-free survival; OS: overall survival; SAE: serious adverse event

      Conclusion
      The PARAMOUNT placebo arm showed results consistent with the JMDB homogeneous group treated with pem+cis. The addition of pem continuation maintenance treatment results in a statistically significant increase in OS and PFS. Although there was an increase in the incidence of grade 3/4 toxicities with longer exposure to pem+cis or maintenance pem, the overall incidence remains low, underscoring the relative safety of these treatment regimens.