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K.D. Wilner
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O16 - NSCLC - Targeted Therapies III (ID 115)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:H.A. Wakelee, L. Crino
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Auditorium, Level 1
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O16.05 - Efficacy, safety, and patient-reported outcomes (PROs) with crizotinib versus chemotherapy in Asian patients in a phase III study of previously treated advanced <em>ALK</em>-positive non-small cell lung cancer (NSCLC) (ID 2818)
11:15 - 11:25 | Author(s): K.D. Wilner
- Abstract
- Presentation
Background
Crizotinib is a potent selective ATP-competitive ALK inhibitor demonstrating a high ORR in patients with advanced ALK-positive NSCLC. The main objective of the present post hoc analyses was to compare the impact of crizotinib on efficacy, safety, and PROs with that of standard second-line chemotherapy in a subgroup of patients of Asian ethnicity from the ongoing phase III study PROFILE 1007.Methods
Patients with stage IIIB/IV ALK-positive NSCLC who had received one prior platinum-based regimen were randomized to open-label crizotinib (250 mg PO BID) or chemotherapy (pemetrexed 500 mg/m[2] or docetaxel 75 mg/m[2], IV q3w). In these subgroup analyses, PFS and ORR based on independent radiologic review, OS, safety, and PROs were evaluated. PROs were assessed at baseline, on day 1 of each cycle, and at end of treatment using the validated cancer-specific questionnaire EORTC QLQ-C30 and its LC module QLQ-LC13. Time to deterioration (TTD) was defined as the time from randomization to the earliest time with a ≥10-point increase from baseline (worsening) in pain in chest, dyspnea, or cough. Repeated measures mixed-effects analyses were performed to compare change from baseline scores between the treatment arms.Results
Of 347 patients randomized, 45% were of Asian ethnicity (crizotinib, n=79; chemotherapy, n=78 [pemetrexed, 50; docetaxel, 27; no treatment, 1]). At data cutoff (March 2012), 52 Asian patients (crizotinib, 41; chemotherapy, 11) were continuing on treatment. PFS was significantly longer with crizotinib than with chemotherapy (median 8.1 vs. 2.8 months; HR, 0.53; P=0003). The ORR on crizotinib (75%) was significantly higher than on chemotherapy (22%; P<0.0001). In an interim analysis, median OS had not yet been reached in the crizotinib arm and was 22.8 months in the chemotherapy arm (HR, 0.89; P=0.347, noting that in the overall study population, only 40% of planned events had occurred and 64% of patients in the chemotherapy arm subsequently received crizotinib in another study). The most common all-causality AEs with crizotinib were diarrhea (70%), vision disorder (68%), and nausea (66%) and with chemotherapy were decreased appetite (40%), nausea (39%), and fatigue (35%). Crizotinib treatment was associated with a significantly longer TTD in LC symptoms compared with chemotherapy (median 4.2 vs. 1.6 months; HR, 0.66; 95% CI, 0.44−0.98; P=0.037). A significantly greater improvement from baseline was observed with crizotinib for global QOL (P<0.05), cough (P<0.001), dyspnea (P<0.001), pain in arm or shoulder (P<0.001), pain in chest (P<0.001), pain in other parts (P<0.05), fatigue (P<0.05), insomnia (P<0.05), and pain (P<0.001). A significantly greater improvement was observed with crizotinib compared with chemotherapy for emotional functioning (P<0.05), physical functioning (P<0.05), hair loss (P<0.001), and sore mouth (P<0.05). A significantly greater deterioration was observed in the crizotinib arm for constipation (P<0.05) and diarrhea (P<0.001) compared with chemotherapy.Conclusion
Consistent with previously reported results in the overall study population, crizotinib treatment showed significantly greater improvement in PFS, ORR, patient-reported LC symptoms, and global QOL compared with chemotherapy in a subgroup of patients of Asian ethnicity with previously treated advanced ALK-positive NSCLC, confirming the utility of crizotinib in this patient population.Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.11-041 - Effect of treatment duration on incidence of adverse events (AEs) in a phase III study of crizotinib versus chemotherapy in advanced <em>ALK</em>-positive non-small cell lung cancer (NSCLC) (ID 2900)
09:30 - 09:30 | Author(s): K.D. Wilner
- Abstract
Background
In the ongoing global randomized phase III study PROFILE 1007, the oral ALK inhibitor crizotinib improved progression-free survival, response rate, and global quality of life compared with single-agent chemotherapy in patients with advanced, previously treated ALK-positive NSCLC. While hematologic toxicities were more common with chemotherapy, a greater number of non-hematologic toxicities were reported with crizotinib. Several factors may have complicated the comparison of AEs, including longer treatment duration with crizotinib, standard use of prophylactic medications with chemotherapy but not with crizotinib, and a higher rate of continuing treatment beyond RECIST-defined progressive disease with crizotinib. Here we examine whether differences in treatment duration may have impacted the incidences of selected AEs and non-fatal serious AEs (SAEs) observed in this study.Methods
In PROFILE 1007, 172 patients received crizotinib 250 mg orally BID and 171 patients received chemotherapy (pemetrexed 500 mg/m[2] or docetaxel 75 mg/m[2], both IV q3w). AEs were classified and graded using CTCAE v4.0. For this analysis, AEs of interest included those occurring in ≥10% of patients with ≥5% absolute difference between treatment groups, as well as non-fatal SAEs. To evaluate the potential impact of differential treatment duration on these AEs, exposure-adjusted incidence rates were calculated using person-years of exposure (PYE; the sum of the individual person-years at risk for a particular AE).Results
Median treatment duration was almost three-fold longer with crizotinib (31 weeks) versus chemotherapy (12 weeks). Incidences and exposure-adjusted incidence rates of AEs of interest are shown in the table below. After accounting for treatment duration, the rates of nausea, constipation, elevated transaminases, edema, upper respiratory infection, dizziness, pulmonary embolism, hypokalemia, and non-fatal SAEs were comparable between the crizotinib and chemotherapy groups. The rates of diarrhea, vision disorder, vomiting, dysgeusia, and syncope were significantly higher with crizotinib. Exposure-adjusted incidence rates for other AEs, as well as additional analyses to account for treatment duration will be presented.
[a]For differences in incidence rates, two‑sided.[b]Clustered term.Crizotinib (n=172) Chemotherapy (n=171) AE Incidence (%) Incidence rate/1000 PYE Incidence (%) Incidence rate/1000 PYE P value[a] Diarrhea 60 1848 19 592 <0.0001 Vision disorder[b] 60 2449 9 268 <0.0001 Nausea 55 1577 37 1527 0.842 Vomiting 47 1083 18 561 0.001 Constipation 42 832 23 789 0.789 Elevated transaminases[b] 38 716 15 470 0.056 Edema[b] 31 568 16 473 0.430 Dysgeusia 26 463 9 269 0.045 Upper respiratory infection[b] 26 419 13 401 0.865 Dizziness[b] 22 346 8 236 0.195 Pulmonary embolism[b] 6 78 2 62 0.686 Hypokalemia 5 70 2 63 0.846 Syncope 3 39 0 0 0.025 Non-fatal SAEs 29 440 21 640 0.105 Conclusion
This initial analysis suggests that differences in treatment duration between two drugs may have a significant impact when comparing AE profiles. Depending on the safety profiles of the two drugs, analyses to account for treatment duration may be appropriate when a large disparity has been observed.
