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W.J. John



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-034 - Weight Gain as a Prognostic Factor on Patient Outcomes<br /> In Advanced, Nonsquamous, Non-small Cell Lung Cancer (ID 1905)

      09:30 - 09:30  |  Author(s): W.J. John

      • Abstract

      Background
      Patients with advanced/metastatic non-small cell lung cancer (NSCLC) have a poor prognosis and low survival rates. One of the first notable symptoms of advanced lung cancer is unexplained weight loss. We evaluated weight gain (> 5% post baseline), as an early prognostic factor for clinical outcome, in advanced nonsquamous, NSCLC patients.

      Methods
      This retrospective analysis reports on three randomized phase III studies with survival and response data from a total of 2301 advanced, nonsquamous NSCLC patients who received pemetrexed or other chemotherapy plus a platinum or targeted agent, as first-line therapy. Body weight was recorded before and after treatment by each study’s schedule. Baseline weight was defined as the last non-missing weight measure before first treatment. Post baseline weight was defined as the maximum weight measured after starting treatment. Patients were analyzed using log-rank test and adjusted Cox modeling to assess the relationship between weight gain and overall survival (OS) and progression-free survival (PFS). Logistic regression was used to assess the association between baseline covariates and post-baseline weight gain.

      Results
      Patients were a mean age of 61 years (range 26 – 86) and most were of Caucasian descent (77.0%). A majority of patients had adenocarcinoma (73.8%), were male (59.8%) with an ECOG performance status (PS) of 0/1/2 (38.5%/60.2%/1.4%). Many patients were smokers or former smokers (55.7%) with Stage IV disease (83.1 %), according to the American Joint Committee on Cancer, editions. 5/6 and had an average weight at baseline of 71.4 kg. A total of 421 (18.3%) patients had a >5% increase in weight (>5% subgroup) after baseline with a statistically significant increase in OS and PFS. Median OS was 16.7 months for patients in the >5% subgroup versus 10.7 months for patients who gained <5% weight (< 5% subgroup; [n=1880]; p<0.001). PFS was 6.9 months for the >5% subgroup versus 4.8 months for <5% subgroup; p<0.001). Differences in overall response rate (ORR = CR + PR) and disease control rate (DCR = CR + PR + SD) were also significant. ORR was 50.8% for >5% subgroup versus 25.4% for < 5% subgroup (p<0.001). DCR was 91.5% for >5% subgroup and 63.6% for <5% subgroup (p<0.001). Cox modeling revealed patients in the >5% subgroup had significantly longer survival (HR=0.56, [95% CI 0.49-0.64]; p<0.001) than patients with <5% subgroup, after adjusting for baseline age (<65 versus 65), sex, ECOG PS (0 versus 1/2), histology (adenocarcinoma versus others), and study. Similar significant results were also found for PFS. Logistic regression indicated a significant association between weight gain and age. More patients aged <65 had a >5% weight gain (p<0.001).

      Conclusion
      This exploratory analysis showed that substantial weight gain (>5%) occurred after initiation of platinum-based chemotherapy in approximately 20% of advanced/metastatic, nonsquamous NSCLC patients. There was a positive correlation between weight gain and improved, OS, PFS and response in patients treated in these phase III studies.

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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): W.J. John

      • 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): W.J. John

      • 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.