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J. Zhang
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MINI 31 - ALK (ID 158)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 3
- Moderators:S. Malik, I. Ou
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 1a-1f
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MINI31.01 - Diverse Characteristics of ALK+ NSCLC Patients in the United States (ID 1383)
18:30 - 20:00 | Author(s): J. Zhang
- Abstract
- Presentation
Background:
ALK rearrangements in non-small cell lung cancer (NSCLC) have been associated with younger age of onset, East Asian ethnicity, non- or light-smoking history, and adenocarcinoma histology. The objective of this study was to evaluate data from two retrospective multicenter chart review studies conducted in 2013 and 2014 to assess characteristics of ALK+ NSCLC patients and further understand the epidemiology of ALK rearrangements in NSCLC patients.
Methods:
This analysis included data from two chart review studies of patients diagnosed with locally-advanced or metastatic ALK+ NSCLC conducted among two separate panels of US oncologists. In the first study conducted in September and October 2013, 27 oncologists contributed data on 273 patients; in the second study conducted between July and November 2014, 49 oncologists contributed data on 153 patients. In both studies, collected information included the age at diagnosis of NSCLC, sex, ethnicity, smoking history at primary NSCLC diagnosis, and tumor histology. Data from these studies were analyzed to assess ALK+ NSCLC patient characteristics.
Results:
Patients from the 2014 cohort tended to be younger than patients from the 2013 cohort at diagnosis of locally-advanced or metastatic NSCLC (Table). In both cohorts, a little over half of the patients were male. Racial composition was diverse in both patient groups. Patients had varied smoking histories in both studies, with approximately one third of patients reported as never-smokers, one third as light smokers, and one third as moderate/heavy smokers. Tumor histology was heterogeneous in both cohorts. However, a particularly large proportion of patients in the 2014 cohort had squamous cell histology (14%).Table. Characteristics of ALK+ NSCLC Patients from the 2013 and 2014 Studies
Notes: IQR = inter-quartile range [1] Wakelee HA, Sasane M, Zhang J, et al. Description of ALK+ NSCLC patient characteristics and ALK testing patterns. J Clin Oncol 32:5s, 2014 (suppl; abstr 8062). [2] Reported at primary NSCLC diagnosis. [3] Includes patients with unreported smoking history as well as 16 former smokers in the 2014 study with unknown smoking histories.2013 Study[1] N=273 2014 Study N=153 Age (years), median (IQR) 67 (58-72) 59 (52-67) Male (%) 52% 57% Race/Ethnicity (%) Caucasian 59% 63% Black/African American 18% 14% Asian 13% 14% Hispanic/Latino 8% 2% American Indian/Alaska Native 1% 6% Unknown 0% 1% Smoking History[2] (%) Never 33% 27% Light 33% 24% Moderate/heavy 33% 37% Unknown[3] 1% 13% Cancer Histology[2] (%) Adenocarcinoma 81% 65% Squamous cell carcinoma 3% 14% Large cell carcinoma 5% 8% Mixed 11% 9% Unknown 0% 4%
Conclusion:
Assessment of patient characteristics in the two chart reviews suggests that ALK+ NSCLC patients may have diverse characteristics with varied racial composition, smoking histories, and tumor histology to an extent not previously detected. These results suggest that physicians may be testing NSCLC patients more frequently, yielding more diverse histology than expected among ALK+ tumors. Molecular testing could be informative for all newly diagnosed NSCLC patients, including patients with squamous cell histology.
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MINI31.02 - Real-World Characteristics and Outcomes for ALK+ NSCLC in Korea (ID 535)
18:30 - 20:00 | Author(s): J. Zhang
- Abstract
- Presentation
Background:
Clinical trials have shown superior efficacy of ALK inhibitors compared with chemotherapies for patients diagnosed with ALK+ non-small cell lung cancer (NSCLC). In Korea, crizotinib was approved for ALK+ NSCLC in 2011 but is not yet reimbursed. The objective of this study was to describe real-world patient characteristics, ALK testing and treatment patterns, and survival among Korean patients diagnosed with locally-advanced or metastatic ALK+ NSCLC.
Methods:
A retrospective patient chart review was conducted in two major cancer centers in Korea. Participating physicians (N=4) reviewed patient charts and reported patient characteristics, ALK testing and treatment patterns, and survival of patients diagnosed with ALK+ locally-advanced or metastatic NSCLC. ALK inhibitor treatment duration and overall survival (OS) were estimated using Kaplan-Meier analyses.
Results:
In late 2014, 55 ALK+ NSCLC patients were identified for this study. The median follow-up time among these patients was 24.8 months. The median age at locally advanced or metastatic NSCLC diagnosis was 60 years (interquartile range: 52 - 67); 53% of patients were female, 51% were never-smokers, 2% were former smokers, 33% were current smokers, 15% had unknown smoking status, and 98% were diagnosed with adenocarcinoma. At primary diagnosis, 67% of patients had metastatic disease. ALK rearrangement was confirmed by fluorescent in situ hybridization (78%) or immunohistochemistry (22%). 27% of patients had their ALK rearrangement detected more than three months after their locally-advanced or metastatic diagnosis. The majority of patients received initial systemic chemotherapy; only 13% received an ALK inhibitor in the first-line, and 62% received an ALK inhibitor by the end of follow-up. Out of 30 patients who received crizotinib, 83% discontinued (median duration of 6.3 months) and 13% died while still on crizotinib. Of those who discontinued, 32% switched to chemotherapy, 16% switched to a different ALK inhibitor, and 52% received no further antineoplastic therapy. After discontinuing crizotinib, the median OS was 4.3 months.
Conclusion:
In this study of locally-advanced or metastatic ALK+ NSCLC patients in Korea, OS was poor following discontinuation of crizotinib with a median survival of 4.3 months. Additionally, many patients had delays in receiving ALK testing. Among patients who failed crizotinib treatment, over half received no further antineoplastic therapy. These findings suggest the need to provide timely access to ALK testing and effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.
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MINI31.13 - Symptoms and QOL with Ceritinib in ALK+ NSCLC Patients with/without Brain Metastases (ID 1655)
18:30 - 20:00 | Author(s): J. Zhang
- Abstract
Background:
In the pivotal ASCEND-1 study, ceritinib, an anaplastic lymphoma kinase inhibitor (ALKi), showed clinical activity in patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC), including in patients with brain metastases (BrM). Here, patient-reported outcomes (PROs) from the recently reported ASCEND-2 study (NCT01685060) are described for chemotherapy- and ALKi-pretreated patients with ALK+ NSCLC with and without baseline BrM
Methods:
In ASCEND-2, adult patients with ALK+ NSCLC previously treated with chemotherapy and an ALKi (crizotinib) received oral ceritinib 750 mg daily. PROs were assessed at baseline and Day 1 of treatment cycles 2, 3, and every two cycles thereafter (1 cycle=28 days), using the Lung Cancer Symptom Scale (LCSS) and EORTC quality of life and lung cancer surveys (QLQ-C30 and QLQ-LC13, respectively). Data were analyzed by presence/absence of baseline BrM. Data beyond cycle 9 are not reported due to small sample sizes.
Results:
All 140 patients enrolled (median age [range] 51 [29–80] years; 50.0% male), had received ≥2 antineoplastic regimens and 100 (71.4%) had BrM at baseline. At data cutoff (13 August 2014), median follow-up was 11.3 months. PRO questionnaire compliance was at least 91.2% up to cycle 9. In the overall patient population, investigator-assessed disease control rate (DCR) was 77.1% and median duration of response (DOR) 9.7 months. Investigator-assessed whole-body DCR [95% confidence interval (CI)] in patients with and without baseline BrM was 74.0% [64.3, 82.3] and 85.0% [70.2, 94.3], respectively, while DOR [95% CI] was 9.2 [5.5, 11.1] and 10.3 [7.4, 16.6] months, respectively. Analysis of PROs data demonstrated that treatment with ceritinib improved lung cancer symptoms in patients with and without baseline BrM (Figure). QLQ-LC13 outcomes were broadly consistent with those of LCSS. In general, mean global quality of life (QLQ-C30) was maintained on treatment for both patient subgroups, with mean change from baseline in QLQ-C30 global health status ranging from -3.06 to +7.25 in patients without baseline BrM and -2.83 to +3.55 in those with baseline BrM. Figure 1
Conclusion:
In patients with ALKi-pretreated ALK+ NSCLC who received prior chemotherapy and ceritinib, clinical efficacy was demonstrated and cancer symptoms were mostly improved, with health-related quality of life generally maintained regardless of presence or absence of baseline BrM.
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ORAL 33 - ALK (ID 145)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:S. Gadgeel
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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ORAL33.02 - Time to Progression and Post-Progression Survival in ALK+ Ceritinib-Treated NSCLC (ID 945)
16:45 - 18:15 | Author(s): J. Zhang
- Abstract
- Presentation
Background:
There is strong interest in evaluating the outcomes of patients who have progressed after failing targeted agents. With different agents, the post-progression survival (PPS) may be either improved or shortened when a longer duration of time-to-progression (TTP) has been observed. This study evaluated the association between TTP and the duration of PPS among adult patients who received ceritinib for the treatment of advanced anaplastic lymphoma kinase-positive (ALK+) NSCLC.
Methods:
Patients experiencing disease progression during two single-arm, open-label, Phase I and II trials of ceritinib (ASCEND-1 [ClinicalTrials.gov Identifier: NCT01283516] and ASCEND-2 [ClinicalTrials.gov Identifier: NCT01685060]) were included in this analysis. For uniformity, all patients analyzed had received crizotinib prior to ceritinib. TTP after the initiation of ceritinib was studied as a predictor for the length of subsequent PPS using Cox proportional hazards models. Adjustments were made for patients’ baseline characteristics, including age, body mass index, gender, race, Eastern Cooperative Oncology Group (ECOG) performance score, number of prior regimens, tumor histology, and presence of brain metastases. A Kaplan-Meier analysis for PPS was performed stratified by shorter (< 6 months) versus longer TTP (≥ 6 months). As a secondary descriptive analysis, associations were quantified between the duration of TTP and the duration of survival (OS) measured as the sum of TTP and PPS.
Results:
Of 181 patients who experienced disease progression during study follow-up, 94% received at least one chemotherapy prior to baseline, 75% had an ECOG performance score greater than zero at screening, and 79 died during subsequent follow-up. In an unadjusted model, each 3 months of longer TTP was associated with a 24% lower hazard of death following progression (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.60-0.96). Results were similar after adjusting for baseline characteristics (HR: 0.77, 95% CI: 0.61-0.97). Patients with TTP ≥ 6 months experienced significantly longer PPS compared to those with TTP < 6 months (median: 9.8 vs. 6.5 months, log-rank p-value < 0.01). This positive relationship between TTP and PPS translated into the duration of OS: each 3 months of longer TTP was associated with a 58% lower hazard of death after adjusting for baseline characteristics (HR: 0.42, 95% CI: 0.32-0.54). Median OS was not reached for patients with TTP ≥ 6 months and was 10.3 months for patients with TTP < 6 months.
Conclusion:
A longer duration of TTP after treatment with ceritinib was significantly associated with both longer duration of PPS and longer OS.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-020 - Symptoms of Bone and Liver Metastases in Patients with ALK+ Non-Small Cell Lung Cancer (NSCLC) (ID 857)
09:30 - 17:00 | Author(s): J. Zhang
- Abstract
Background:
Among patients with ALK+ NSCLC who develop metastases, common metastatic sites include brain, bones, and liver. Although the symptomatic profile of ALK+ NSCLC patients with brain metastases is well documented, information remains limited for patients with bone metastases or liver metastases.
Methods:
Data from 2 large US administrative claims databases—IMS LifeLink Health Plan Claims (01/2001 – 03/2014) and Truven Health Analytics MarketScan (01/2002 – 09/2012)—were pooled for this retrospective study. Among adult patients with a lung cancer diagnosis, ALK+ NSCLC patients were identified based on prescription fills for crizotinib. Patients were analyzed if they had ≥60 days of follow-up before and ≥30 days after the bone metastasis or liver metastasis diagnosis date.
Results:
A total of 231 ALK+ NSCLC patients were selected: 191 had bone metastasis and 104 had liver metastasis. For the bone metastasis sample, median age was 54.9 years, 39.3% were male, and median time from first lung cancer diagnosis to the bone metastasis diagnosis was 30 days. The frequency of symptoms frequently associated with bone metastasis increased after bone metastasis diagnosis compared to before. Common skeletal-related events included pathologic fractures (before: 0.5% vs. after: 12.6%), spinal cord compression (2.6% vs. 5.2%), and bone radiation therapy (12.6% vs. 62.3%).Other common symptoms were weakness/fatigue (before: 24.6% vs. after: 46.6%), anemia (10.5% vs. 33.0%), back pain (8.4% vs. 22.5%), bowel dysfunction (6.8% vs. 20.9%), and neoplasm-related pain (0.0% vs. 14.1%). For the liver metastasis sample, median age was 54.0 years, 42.3% were male, and median time from first lung cancer diagnosis to first liver metastasis diagnosis was 151 days. The frequency of symptoms frequently associated with liver metastasis also increased compared to before liver metastasis diagnosis, where most common symptoms were nausea/vomiting (before: 21.2% vs. after: 42.3%), abdominal pain (20.2% vs. 34.6%), fever/sweating (6.7% vs. 27.9%), edema (6.7% vs. 25.0%), jaundice (0.0% vs. 3.8%), and fatigue (29.8% vs. 46.2%).
Conclusion:
ALK+ NSCLC patients experience an increased symptomatic burden after developing bone metastasis or liver metastasis. Further research is warranted to analyze the impact of the symptomatic burden on patient quality of life and other outcomes as well as the potential benefit of instituting second-generation ALK-inhibitors earlier in the treatment course.
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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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P2.01-029 - Physician Decision-Making on Modifying or Discontinuing Crizotinib in <em>ALK</em>+ NSCLC: A Survey of US Physicians (ID 1582)
09:30 - 17:00 | Author(s): J. Zhang
- Abstract
Background:
Crizotinib has been commercially available since August 2011 for the treatment of locally-advanced or metastatic ALK+ non-small cell lung cancer (NSCLC). In April 2014, a second-generation ALK inhibitor, ceritinib, was approved in the US for use after intolerance to or progression on crizotinib. Tumor progression, which varies by anatomical site and extent, is complex and evolves over time, often with insidious onset. Considering this heterogeneity, it is currently unclear at which point physicians may decide to change therapy. The objective of this study was to evaluate physicians’ decision-making with regard to determining progression during crizotinib treatment of locally-advanced or metastatic ALK+ NSCLC. This research question is particularly relevant with the introduction of new, effective treatment options available to patients who progress on first-line ALK inhibitor therapy.
Methods:
In July-November 2014, US oncologists were invited to respond to a survey regarding their decision-making with regard to treatment changes following progression on crizotinib for patients with locally-advanced or metastatic ALK+ NSCLC. Information was also collected on the characteristics of their practice.
Results:
Of the 34 oncologists who responded to the survey, 59% were from private practice, 26% were from an academic practice, and 15% were from an institutional practice. In terms of practice size, 53% were from small/intermediate practices of 2-9 oncologists, and the rest were from larger practices. Half (50%) of physicians had their practice in an urban setting; 35% were in a suburban and 15% were in a rural setting. Responding physicians had been in practice for an average of 12 years. When asked to indicate all of the clinical scenarios for which they would modify or discontinue crizotinib therapy, 62% of the physicians indicated that they would do so following disease progression detected on scan; 53% following either new or worsening symptoms; 29% following the development of new metastases in the brain; 35% following the development of new metastases elsewhere; 29% following onset of a paraneoplastic neurological disorder; and 26% following lack of improvement of patient's symptoms.
Conclusion:
The study suggests there is substantial heterogeneity in the clinical scenarios physicians would consider for modifying or discontinuing therapy after progression on crizotinib. These findings highlight the need for further clinical guidance with regard to the early identification of progression on crizotinib, and in particular, for a better understanding of the optimal point to switch from crizotinib when patients present with different manifestations of disease progression.
