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DosingSafetyClinical TrialsClinical TrialsXALKORI Clinical TrialsROS1+ NSCLC: PROFILE 1001ALK+ NSCLC: PROFILE 1014

Real World Evidence

Real World EvidenceReal World EvidenceSequential XALKORI® and Ceritinib in ALK+ NSCLCXALKORI® and Post-Progression Treatment in ALK+ NSCLC


The information on this website is based on data from adult patients with ALK (anaplastic lymphoma kinase)-positive / ROS 1-positive advanced NSCLC (non small cell lung cancer) treated with XALKORI®(crizotinib), produced in line with the XALKORI®(crizotinib) Summary of Product Characteristics. XALKORI® (crizotinib) Prescribing Information click here. Adverse event reporting information can be found at the bottom of the page.

PROFILE 1014: XALKORI® for ALK+ Advanced NSCLCStudy Design

PROFILE 1014 was a multicentre, randomised, open-label Phase III trial comparing XALKORI® with standard first line chemotherapy in 343 adult (Age 18 or older) patients with previously untreated anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). The trial demonstrated superiority of first line Crizotinib over pemetrexed plus platinum based chemotherapy1

The study showed a significant improvement in median progression free survival (10.9 months vs 7 months), P<0.001, and a significantly higher objective response rate (74% vs 45%), P<0.001 in the Crizotinib arm1.

Adapted from Solomon BJ, et al. N Eng J Med. 2014.1,2
* ALK status determined using standard ALK break-apart fluorescent in-situ hybridisation assay.1  

Baseline Patient Characteristics
The baseline patient characteristics for the intention-to-treat population of the PROFILE 1014 study (N=343) were as follows:​1
Characteristic XALKORI® (n=172) Chemotherapy (n=171)
Age (years)
Median 52 54
Range 22-76 19-78
Sex (%)*
Male 40 37
Female 60 63
Race (%)*†
White 53 50
Asian 45 47
Other 2 4
Smoking status (%)*
Never smoked 62 65
Former smoker 33 32
Current smoker 6 3
Histologic characteristics of tumour (%)*
Adenocarcinoma 94 94
Non-adenocarcinoma 6 6
ECOG performance status (%)*‡
0 or 1 94 95
2 6 5
Extent of disease (%)*
Locally advanced 2 2
Metastatic 98 98
Time since first diagnosis (months)
Median 1.2 1.2
Range 0-114.0 0-93.6
Brain metastases present (%)*
Yes 26 27

 Adapted from Solomon BJ, et al. N Eng J Med. 2014.1

* Percentages may not total 100 due to rounding.
† Race was self-reported.1
‡ ECOG was assessed at the time of screening; the score was not reported for one patient in the XALKORI® group. Scores ranged from 0 to 5, with higher scores indicating increased disability.1

Initial Study Results (data cutoff: November 30, 2013)

The pre-specified number of events of progression or death to detect a 50% improvement in the primary endpoint was estimated to be 229. These were reached and the data cutoff was determined to be November 30, 2013.1

At the time of data cutoff, the median overall survival (OS) had not been reached for either arm. Median duration of follow-up for OS was 17.4 months for XALKORI® and 16.7 months for chemotherapy. Median duration of treatment was 10.9 months (95% CI: 0.4-34.3 months) for XALKORI® and 4.1 months (95% CI: 0.7-6.2 months) for chemotherapy.1

Primary Endpoint: Progression-Free Survival (ITT population)

At the time of follow-up, XALKORI® significantly prolonged median PFS in patients with ALK+ advanced NSCLC compared to chemotherapy (10.9 months vs. 7.0 months, respectively). XALKORI® reduced the risk of progression or death by 55% compared to chemotherapy (hazard ratio [HR]: 0.45 [95% confidence interval (CI): 0.35-0.60]; p<0.001).*1

Adapted from Solomon BJ, et al. N Eng J Med. 2014.1 
*Median duration of follow-up for OS was 17.4 months for XALKORI(R) and 16.7 months for chemotherapy. Median duration of treatment was 10.9 months (95% CI: 0.4-34.3 months) for XALKORI® and 4.1 months (95% CI: 0.7-6.2 months) for chemotherapy.1

At the time of follow-up, the HR favoured XALKORI® over chemotherapy for most pre-specified subgroups.1

HR by pre-specified subgroup*1

Adapted from Solomon BJ, et al. N End J Med. 2014.1
*Median duration of follow-up for OS was 17.4 months for XALKORI(R) and 16.7 months for chemotherapy. Median duration of treatment was 10.9 months (95% CI: 0.4-34.3 months) for XALKORI® and 4.1 months (95% CI: 0.7-6.2 months) for chemotherapy.1

Intracranial Efficacy

Of 343 patients in the ITT population, 79 (23%) had treated brain metastasis at baseline identified by IRR and 263 (77%) did not.2

Baseline metastases at baseline Treatmnt arm (n) Median PFS Hazard ratio
(95% CI)
P-value
Yes XALKORI® (n=39) 9.0 months 0.40 (95% CI: 0.23-0.69) <0.001
Chemotherapy (n=40) 4.0 months
No XALKORI® (n=132) 11.1 months 0.51 (95% CI: 0.38-0.69) <0.001
Chemotherapy (n=131) 7.2 months

XALKORI® was shown to significantly improve median PFS over chemotherapy for patients without and with treated brain metastases at baseline:2
•    Brain metastases present at baseline (HR: 0.40 [95% CI: 0.23-0.69]; p<0.001) 
•    Brain metastases absent at baseline (HR: 0.51 [95% CI: 0.38-0.69]; p<0.001)

Objective Response Rate

At time of follow-up, the XALKORI® arm (n=172) demonstrated a significantly higher objective response rate of 74% compared to a 45% ORR in the chemotherapy arm (p<0.001) (n=171).*1

Adapted from Solomon BJ, et al. NEJM. 2014.1
*Median duration of follow-up for OS was 17.4 months for XALKORI(R) and 16.7 months for chemotherapy. Median duration of treatment was 10.9 months (95% CI: 0.4-34.3 months) for XALKORI® and 4.1 months (95% CI: 0.7-6.2 months) for chemotherapy.1

Furthermore, XALKORI® offered a rapid and durable response compared to chemotherapy:
•    Time to response. 1.4 months (95% CI: 0.6-9.5 months) with XALKORI® vs. 2.8 months (95% CI: 1.2-8.5 months) with chemotherapy* 
•    Duration of response: 11.3 months (95% CI: 8.1-13.8 months) with XALKORI® vs. 5.3 months (95% CI: 4.1-5.8 months) with chemotherapy 

* The time to tumour response was calculated from the date of randomisation to the date of the first documentation of a partial or complete response as determined by independent radiologic review.1
† The duration of response was calculated from the date of the first documentation of a partial or complete response to the date of RECIST-defined progression or death, with the use of the Kaplan-Meier method.1

Quality of Life

XALKORI® significantly improved patients' global quality of life compared to chemotherapy (p<0.001), and was associated with a significantly greater improvement from baseline in physical, social, emotional and role functioning domains (p<0.001).* A change of 10 points or more is considered to be a clinically meaningful change.

There was also a significantly greater overall reduction from baseline with XALKORI® compared to chemotherapy in symptoms of pain, dyspnoea and insomnia (p<0.001).*1

Adapted from Solomon BJ, et al. N Eng J Med. 2014.
*As assessed using the QLQ-C30. Patient-reported outcomes were assessed at baseline, on days 7 and 15 of cycle 1, on day 1 of every subsequent cycle, and at the end of treatment. Scores on each scale ranged from 0 to 100. For global quality of life and functioning domains, higher scores indicate better global quality of life or functioning. For symptoms, lower scores indicate reduction in symptoms.1 

Final OS Analysis (data cutoff: November 30, 2016)OS in the ITT population*3At follow-up, median OS was not reached in the XALKORI® arm and 47.5 months with chemotherapy. XALKORI® demonstrated a numerical, though not statistically significant, improvement in OS compared to chemotherapy (HR: 0.760 [95% CI: 0.548-1.053]; p=0.0978).*3

Adapted from Solomon BJ, et al. J Clin Oncol. 2018.3
* Median follow-up for final OS was approximately 46 months for both the XALKORI® and chemotherapy arms. Median treatment duration of treatment with XALKORI® was 10.9 months and with chemotherapy was 4.1 months.3

OS Analysis Adjusting for CrossoverCrossover was permitted in the study. 82.4% of patients in the chemotherapy arm crossed over to XALKORI® as their first subsequent follow-up treatment and 19.2% of patients in the XALKORI® arm crossed over to chemotherapy as their first subsequent follow-up treatment.3 The rank-preserving structural failure time model (RPSFTM) was used to adjust for the effect of crossover on OS and allow for an unbiased estimation of treatment effect on OS as if there had been no crossover.3After adjusting for crossover using the RPSFTM, OS was longer with crizotinib than with chemotherapy (HR, 0.346; 95% bootstrap CI, 0.081 to 0.718).*3 

Adapted from Solomon BJ, et al. J Clin Oncol. 2018.3
* Median follow-up for final OS was approximately 46 months for both the XALKORI® and chemotherapy arms. Median treatment duration with XALKORI® was 14.7 months and with chemotherapy was 10.9 months.3

​​​​​ALK: anaplastic lymphoma kinase, AUC: area under the curve, BID: twice a day, CI: confidence interval, ECOG: Eastern Cooperative Oncology Group, EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer quality of life questionnaire-core 30, EQ-5D: EuroQol group 5-dimension self-report questionnaire (EQ-5D), FISH: fluorescence in situ hybridisation, HR: hazard ratio, IC TTP: intra cranial time to tumour progression, IRR: independent radiologic review, ITT: intention to treat, NSCLC: non-small-cell lung cancer, NR: not reached, ORR: objective response rate, OS: overall survival, PFS: progression-free survival, PO: by mouth, PS: performance score, QOL: quality of life, RECIST: response evaluation criteria in solid tumours, RPSFTM, rank preserving structural failure time model, TKI: tyrosine kinase inhibitor

References

Solomon BJ, Mok et al. N Eng J Med. 2014;371(23):2167-2177Solomon BJ, Cappuzzo et al. J Clin Oncol. 2016;34(24):2858-2865.Solomon BJ, Dong et al. J Clin Oncol. 2018;36:2251-2258.
PP-XLK-IRL-0261 February 2024 Legal Category S1A Further information is available on request
XALKORI® clinical trialsSafety

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