The DOI matches its Crossref record; 15 of the 33 references it cites were found in a registry or an index, and 18 are not checked yet; none of the 17 sources its claims cite is checked for support yet.
First-Line Crizotinib versus Chemotherapy in ALK -Positive Lung Cancer
Open accessAbstract
BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. METHODS: We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review. RESULTS: Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).
Checked 2026-10-06 · 18 references not checked yet
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48 Own result · 16 Own method · 12 Not checked yet · 5 Own interpretation · 1 Check pending · 1 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Grade 3 or 4 elevations of aminotransferase levels occurred in 24 patients in the crizotinib group (14%) and in 4 patients in the chemotherapy group (2%), but these elevations were managed primarily with dose interruptions or dose reductions.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plainn = 24- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Intracranial lesions progressed or new intracranial lesions developed in 25 patients in the crizotinib group and in 26 patients in the chemotherapy group (15% each).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Efficacy
plainn = 25- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Among patients randomly assigned to crizotinib, 74 of 89 patients with progressive disease (83%) continued to receive crizotinib beyond disease progression for a median of 3.0 months (range, 0.7 to 22.6).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2172
plainn = 89- Asserted: passes — The authors put it forward as true.
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In the paper
“No deaths from hepatic dysfunction occurred.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Median overall survival was not reached in either group”
- Also stated in: § Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival. · plain
“the median overall survival was not reached in either group.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plainn = 343- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival. · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hazard ratio favored crizotinib across most subgroups defined according to stratification factors and other baseline characteristics (Fig. 1C).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Efficacy
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 171 patients randomly assigned to chemotherapy, 120 (70%) subsequently received crizotinib treatment.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival.
plainn = 171- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P = 0.36);”
- Also stated in: § Efficacy · plain
“There was no significant difference in overall survival between patients in the crizotinib group and those in the chemotherapy group at the time of the progression-free survival analysis (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P = 0.36) (Fig. 1B)”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plainn = 343- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Efficacy · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Four hepatic events resulted in permanent discontinuation of treatment in the crizotinib group:”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Objective response rates were 74% and 45%, respectively (P<0.001).”
- Also stated in: § Efficacy · plain
“The objective response rate was significantly higher with crizotinib than with chemotherapy (74% [95% CI, 67 to 81] vs. 45% [95% CI, 37 to 53], P<0.001) (Table 2).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plaindirectn = 343 ·- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Efficacy · plain
- It may state two separate claims as one. 28
- Probably not a substantial claim. 22
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At data cutoff, 79 patients who had been randomly assigned to crizotinib (46%) and 62 patients assigned to chemotherapy who had crossed over to crizotinib (36%) were still receiving crizotinib therapy.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2172
plainn = 79- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 172 patients assigned to crizotinib, 21 (12%) subsequently received platinum-based chemotherapy.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival.
plainn = 172- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The median duration of re-sponse was 11.3 months and 5.3 months, respectively.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Efficacy
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001).”
- Also stated in: § Efficacy · plain
“The median progression-free survival was 10.9 months (95% confidence interval [CI], 8.3 to 13.9) among patients in the crizotinib group, as compared with 7.0 months (95% CI, 6.8 to 8.2) among patients in the chemotherapy group (hazard ratio”
- Also stated in: § Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival. · plain
“The median progressionfree survival was 10.9 months with crizotinib as compared with 7.0 months with chemotherapy.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plaindirectn = 343- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Efficacy · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The probability of 1-year survival was 84% (95% CI, 77 to 89) in the crizo-tinib group and 79% (95% CI, 71 to 84) in the chemotherapy group.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and the events for which the incidence was at least 5 percentage points higher in the chemotherapy group than in the crizotinib group were fatigue (occurring in 38% of the patients), anemia (in 32%), and neutropenia (in 30%) (Table 3).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most common adverse events of any cause for which the incidence was at least 5 percentage points higher in the crizotinib group than in the chemotherapy group were vision disorder (occurring in 71% of the patients), diarrhea (in 61%), and edema (in 49%);”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The median duration of treatment was 10.9 months (range, 0.4 to 34.3) in the crizotinib group (a median of 16 cycles started [range, 1 to 50]) and 4.1 months (range, 0.7 to 6.2) in the chemotherapy group (a median of 6 cycles of chemotherapy started [range, 1 to 6]).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three patients underwent randomization but received no study treatment, leaving 340 patients in the as-treated population -171 patients in the crizotinib group and 169 in the chemotherapy group (with 91 patients receiving pemetrexed-cisplatin and 78 receiving pemetrexed-carboplatin).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Patients
plainn = 340- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the current study, grade 3 or 4 elevations of aminotransferase levels occurred in 14% of the patients in the crizotinib group and could be managed with dose interruptions or dose reductions.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Crizotinib treatment was also associated with a significantly higher response rate and significantly greater improvements in patient-reported measures of physical functioning, key lung-cancer symptoms (cough, dyspnea, chest pain, and fatigue), and global quality of life.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall survival did not differ significantly between the treatment groups at the time of this analysis, with a relatively small number of deaths reported (26%; 90 of the 343 patients who underwent randomization).”
- Also stated in: § Discussion · plain
“death in the crizotinib group, 0.82 (95% CI, 0.54-1.26)P=0.36 (two-sided stratified log-rank test)”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plainn = 343- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Time to response -mo § Median 1.4 2.8 Range 0.6-9.5 1.2-8.5”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plainn = 172- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The baseline characteristics of the patients and the efficacy outcomes in subgroup analyses of crizotinib versus individual chemotherapy regimens were similar to those in the analysis of the overall population (Table S3 and Fig. S4 in the Supplementary Appendix).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2172
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Duration of response -mo ¶ Median 11.3 5.3 95% CI 8.1-13.84.1-5.8*”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plainn = 172- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a significantly greater overall reduction from baseline with crizotinib than with chemotherapy in the symptoms of pain, dyspnea, and insomnia as assessed with the use of the QLQ-C30 (Fig. 2B) and in the symptoms of dyspnea, cough, chest pain, arm or shoulder pain, and pain in other parts of the body as assessed with the use of the QLQ-LC13 (Fig. 2C) (P<0.001 for all comparisons)”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Patient-Reported Outcomes
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An additional case that met the criteria for Hy's law occurred in a patient in the chemotherapy group after crossover to crizotinib.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plainSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the time of data cutoff, the median duration of follow-up for overall survival was 17.4 months for patients assigned to crizotinib and 16.7 months for those assigned to chemotherapy.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Patients
plainn = 343- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of progression-free survival at 18 months was 31% (95% CI, 23 to 39) in the crizotinib group and 5% (95% CI, 2 to 10) in the chemotherapy group.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Table 1. Baseline Characteristics in the Intention-to-Treat Population.* Figure 1 (facing page). Progression-free and Overall Survival.
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Between January 2011 and July 2013, a total of 343 patients underwent randomization -172 to crizotinib and 171 to chemotherapy (intention-totreat population) (Fig. S1 in the Supplementary Appendix).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Patients
plainn = 343- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“These results were independent of the type of platinum treatment administered, the performance status of the patient, the patient's race, and the presence or absence of brain metastases.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It should be noted that the median survival had not been reached in either group, with a median follow-up of 17 months.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“They define a distinct subgroup of NSCLC that typically occurs in younger patients who have never smoked or have a history of light smoking and that has adenocarcinoma histologic characteristics.[3][4][5]”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2168
What the sources say
- Not checked yetcites [3][4][5]
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In phase 1 and 2 studies, crizotinib treatment resulted in objective tumor responses in approximately 60% of patients with ALK-positive NSCLC and in progression-free survival of 7 to 10 months.[7][8][9]”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2168
What the sources say
- Not checked yetcites [7][8][9]
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Crizotinib is an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases.6”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > 2168
What the sources say
- Not checked yetcites [6] source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We estimated that with 229 events of progression or death, the study would have 85% power to detect a 50% improvement in progression-free survival with crizotinib versus chemotherapy (from 6 months to 9 months), at a one-sided alpha level of 0.025.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomization was stratified according to ECOG performance status (0 or 1 vs. 2), Asian or non-Asian race, and presence or absence of brain metastases.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Study Design and Treatment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Efficacy end points were measured in the intention-to-treat population, which included all patients who underwent randomization.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“As prespecified in the protocol, overall survival was also analyzed with the rank-preserving structural failure time model [20][21][22] to explore the effect of crossover to crizotinib in the chemotherapy group.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
What the sources say
- Not checked yetcites [20][21][22]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: The rank-preserving structural failure time model's assumptions are valid for estimating the effect of crizotinib after crossover adjustment.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Safety evaluations were performed in the astreated population, which included all patients who received at least one dose of study medication.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The primary end point was progression-free survival (the time from randomization to RECISTdefined progression, as assessed by independent radiologic review, or death).”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Study Design and Treatment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All scans were submitted for central independent radiologic review by radiologists who were unaware of the group assignments.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Assessments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Safety results were not adjusted for the shorter duration of treatment in the chemotherapy group.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“† Only events that occurred before crossover to crizotinib are included.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All analyses in the chemotherapy group, with the exception of the analysis of overall survival, included only data collected before crossover to crizotinib.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, in patients with previously untreated ALK-positive NSCLC, crizotinib treatment was superior to pemetrexed-plus-platinum chemotherapy with respect to progression-free survival, objective response rate, reduction of lung-cancer symptoms, and improvement in quality of life.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“† Responses could not be evaluated in 4 patients in each group because of early death.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The efficacy of pemetrexed-based first-line chemotherapy has since been documented in ALK-positive NSCLC, 29,30 a finding that supports this selection.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The safety profile of crizotinib was consistent with that reported earlier in patients with previously treated advanced ALK-positive NSCLC 10 and differed from that observed with chemotherapy.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Discussion
What the sources say
- Not checked yetcites [10] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The protocol was approved by the institutional review board or independent ethics committee at each participating center and complied with the International Ethical Guidelines for Biomedical Research Involving Human Subjects, Good Clinical Practice guidelines, the Declaration of Helsinki, and local laws.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Study Oversight
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“* Adverse events are listed here if they were reported in 15% or more of patients in either treatment group; rates were not adjusted for differences in treatment duration.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient-reported outcomes were evaluated in patients in the intention-to-treat population who also had a baseline assessment and at least one post-baseline assessment.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Tumor responses were assessed with the use of Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and were confirmed by independent radiologic review.”
§ First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer > Safety and Adverse Events
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
The rank-preserving structural failure time model's assumptions are valid for estimating the effect of crizotinib after crossover adjustment.
“As prespecified in the protocol, overall survival was also analyzed with the rank-preserving structural failure time model [20][21][22] to explore the effect of crossover to crizotinib in the chemotherapy group.”
“After adjustment for crossover with the rank-preserving structural failure time model, the hazard ratio for death with crizotinib was 0.60 (95% CI, 0.27 to 1.42)”
The paper relies on this without support.
Most advanced ALK-positive NSCLCs have nonsquamous histologic characteristics.
“Given that most advanced ALK-positive NSCLCs have nonsquamous histologic characteristics, pemetrexed in combination with cisplatin or carboplatin was selected as the standard chemotherapy for this trial.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Across clinical trials of first-line targeted therapy for oncogene-addicted subgroups of NSCLC, rates of objective response [G] typically range between 50% and 83% and complete responses [G] are rare; in addition, some patients exhibit de novo resistance16–26, 28–32, 35.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [24]
In the citing paper
“Even more variable are duration of response to targeted therapy, progression-free survival and overall survival16–26, 28–32, 35.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [24]
In the citing paper
“The EML4-ALK fusion, which confers sensitivity to the ALK TKI crizotinib (1), was detected in 2 samples.”
In the citing paper
“Subsequently, the phase III study PROFILE 1014 compared crizotinib with cisplatin-pemetrexed without maintenance pemetrexed as first-line treatment in ALK-positive advanced NSCC [137], and demonstrated a significantly longer PFS (median of 10.9 versus 7.0 months; HR for progression or death with crizotinib 0.45; 95% CI: 0.35-0.60;P < 0.001) and higher ORR with crizotinib compared with chemotherapy”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [137]
In the citing paper
“This trial of 343 participants reached its primary end point of higher PFS with crizotinib (10.9 v 7 months; HR, 0.454; 95% CI, 0.346 to 0.596; P < .001).”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [54]
In the citing paper
“Survival was not significantly different (P = .36).”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [54]
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Metadata
- Authors
- Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., Iyer, S., Reisman, A., Wilner, K. D., Tursi, J., & Blackhall, F.
- Affiliations
- Chinese University of Hong Kong (HK)
- Seoul National University Hospital (KR)
- Kindai University (JP)
- Florida Hospital Cancer Institute (US)
- Vall d'Hebron Hospital Universitari (ES)
- Ospedale di Livorno (IT)
- Pfizer (United States) (US)
- University of Manchester (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-12-04
- Volume
- 371
- Issue
- 23
- Pages
- 2167-2177
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2099530756
- Cited by
- 3,190
- References
- 33
- Citations by year
- 2026: 92 · 2025: 142 · 2024: 185 · 2023: 220 · 2022: 256 · 2021: 296 · 2020: 302 · 2019: 363 · 2018: 365 · 2017: 375 · 2016: 347 · 2015: 233 · 2014: 10
- FWCI
- 258.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- crizotinib, ALK-positive non-small cell lung cancer, anaplastic lymphoma kinase, ALK inhibitors, first-line therapy, progression-free survival, overall survival, objective response rate, quality of life, adverse events
- MeSH terms
- Pemetrexed, Crizotinib, Anaplastic Lymphoma Kinase, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cisplatin, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Pyrazoles, Pyridines, Carboplatin, Disease-Free Survival, Receptor Protein-Tyrosine Kinases, Protein Kinase Inhibitors, Kaplan-Meier Estimate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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