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M. Provencio
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)
10:56 - 11:07 | Author(s): M. Provencio
- Abstract
- Presentation
Background:
Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.
Methods:
PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).
Results:
Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%) Neutrophils 27 (11.8) 76 (37.6)* Leukocytes 19 (8.3) 29 (14.4) Hemoglobin 6 (2.6) 9 (4.5) Platelets 5 (2.2) 10 (5.0) Febrile neutropenia 7 (3.1) 7 (3.5) Lymphopenia 8 (3.5) 5 (2.5) Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0) Fatigue 2 (0.9) 4 (2.0) Pneumonia 5 (2.2) 0 Esophagitis 0 3 (1.5) *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.
Conclusion:
During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-015 - Malignant Pleural Mesothelioma: Observational and Retrospective Analysis of Spanish Database (BEMME). The Spanish Lung Cancer Group (SLCG) (ID 2355)
09:30 - 09:30 | Author(s): M. Provencio
- Abstract
Background:
Malignant Pleural Mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. Although in Spain asbestos was banned in 2002, it is estimated that occupationally related deaths due to MPM will continue to occur until 2040. BEMME (Base Epidemiológica Mesotelioma Maligno en España) is an observational and retrospective study sponsored by the Spanish Lung Cancer Group that aimed to characterize the patient’s and tumour’s features as well as the treatment modalities of patients diagnosed with mesothelioma in Spain.
Methods:
Clinical records of patients with malignant pleural and peritoneal mesothelioma were retrospectively reviewed to collect epidemiological data, diagnostic tests, treatment modalities and survival data into an electronic and anonymous database. Thirty-five Spanish hospitals participated in the project and 570 mesothelioma patients were included in the BEMME database. Here we present a descriptive analysis of MPM patients based upon these data.
Results:
From January 2008 to December 2013, 538 patients (p) had MPM. Most patients were males (77%) and 74% of patients were ≥ 60 years (60-70y: 33%, >70y: 41%). Most patients (49%) had a performance status 1 at diagnosis. Only 32% of patients were recorded as positive for asbestos exposure and 77% of patients were never-smokers. Dyspnoea (35%) and thoracic pain (26%) were reported as the most frequent symptoms at diagnosis. Epithelioid was the most frequent histological subtype (63%), followed by sarcomatoid (12%), biphasic (8%) and not specified (17%). Disease stages at diagnosis were: stage I, 7%; stage II, 9%; stage III, 17%; stage IV, 45%; not specified, 22%. Surgery was performed in 41p: extrapleural neumonectomy 16p, extended pleurectomy 15p and partial pleurectomy 10p. Palliative pleurodesis was performed in 22% of patients. A total of 70% of patients received chemotherapy (55% palliative, 11 neoadjuvant and 6% adjuvant). The median overall survival (OS) for all patients was 13.2 months (95% CI 12.2 – 15.2). There were no statistically significant differences in OS according to age, gender and asbestos exposure. In the univariate analysis, higher stage (III-IV vs. I-II, p=0.0003) and non-epithelioid subtype (non-epithelioid vs. epithelioid, p=0.00001) were significantly associated with shorter OS.
Conclusion:
In Spain, most MPM patients are diagnosed at advanced stages and are treated with palliative modalities: mainly chemotherapy and pleurodesis. Stage and histologic subtype were prognostic factors for survival. BEMME database is a helpful tool to describe the therapeutic strategies employed in MPM patients in Spain.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-085 - Abemaciclib in Combination with Single Agent Options in Stage IV NSCLC, a Phase 1b Study (ID 125)
09:30 - 09:30 | Author(s): M. Provencio
- Abstract
Background:
Abemaciclib, a cell cycle inhibitor selective for CDK4/6, demonstrated acceptable safety and early clinical activity in metastatic NSCLC, given orally as monotherapy on a continuous schedule. Combinations of abemaciclib showed greater activity compared with monotherapy in KRAS-mutant NSCLC preclinical models. Primary aim of study NCT02079636 was safety/tolerability of combination therapy with abemaciclib; secondary aims included pharmacokinetics and antitumor activity.
Methods:
In this open-label 3+3 dose-escalation study with expansion cohorts, eligibility included stage IV NSCLC, measurable or nonmeasurable disease (RECISTv1.1), ECOG PS ≤1, and 1-3 prior therapies. Abemaciclib was combined with pemetrexed (Part A, nonsquamous, 500 mg/m[2] IV day 1), gemcitabine (Part B, 1250 mg/m[2] IV days 1 and 8), ramucirumab (Part C, 10 mg/kg IV day 1, or 8 or 10 mg/kg IV days 1 and 8) (Q21), or LY3023414 (dual PI3K-mTOR inhibitor) (Part D, 100 mg, 150 mg or 200 mg orally Q12H). In escalation, patients were dosed continuously until progression with abemaciclib at 100 mg (Part D), 150 mg or 200 mg orally Q12H.
Results:
As of February 27, 2015, 70 patients (Parts A-C) received ≥1 dose; 15 patients at 150 mg and 55 patients (including all 39 patients in expansion) at 200 mg Q12H abemaciclib. The MTD was established at 200 mg Q12H abemaciclib for Parts A-C. See Table 1 for treatment-emergent adverse events (TEAEs). Stable disease was observed in 13/23 patients in Part A; 7 unknown, 4/24 patients in Part B; 10 unknown, and 7/23 patients in Part C; 12 unknown. In Parts A-C, 18/70 (26%) patients started ≥4 cycles (Part A=9, Part B=3, Part C=6). Three confirmed PRs were observed: Part B, 1 patient with squamous histology (unknown mutation status), Part C, 1 patient with nonsquamous histology (KRAS mutation positive; EGFR mutation negative), and 1 patient with squamous histology (unknown mutation status). Updated analyses will be presented including Part D and longer term follow-up for Parts A-C through approximately June 2015. Table 1. TEAEs related to treatment (≥20% in ≥1 part)% All grades (% Gr3/4) Part A (n=23) Part B (n=24) Part C (n=23) Diarrhea 65 (4) 50 (17) 52 (9) Fatigue 57 (9) 63 (8) 17 (4) Nausea 35 (0) 50 (4) 48 (9) Neutropenia 61 (61) 50 (33) 17 (4) Anemia 57 (26) 33 (17) 9 (0) Thrombocytopenia 39 (9) 38 (8) 17 (13) Decreased appetite 30 (0) 25 (0) 22 (0) Vomiting 9 (0) 21 (0) 35 (0) Blood creatinine increased 30 (0) 8 (0) 17 (4) Leukopenia 30 (22) 17 (8) 9 (4)
Conclusion:
Abemaciclib combined with single-agents with acceptable toxicity. Safety findings observed in Parts A and B are consistent with AEs expected when combining myelosuppressive compounds with abemaciclib, resulting in an increased myelosuppressive effect. In Part C, safety findings are consistent with those of single-agents. Tumor responses were observed in Parts B and C.
