Trial Outcomes & Findings for Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352) (NCT NCT01077817)

Results Overview

To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.

Recruitment status

COMPLETED

Target enrollment

684815 participants

Primary outcome timeframe

Exposure to study drug at least 720 days before disease onset

Results posted on

2022-02-03

Participant Flow

Participants were not recruited nor enrolled in this study. This study is a retrospective observational study. Data from the GPRD were anonymized and used to develop participant cohorts. All diagnoses and treatments were recorded in the course of routine medical practice.

684,815 women in the General Practice Research Database (GPRD) formed the Overall Study Population. These women met the demographic criteria of being age 55 or older, were born between 1922 and 1955, had more than 720 days experience in the GPRD and at least one of those days fell between 1996 and 2008.

Participant milestones

Participant milestones
Measure	Overall Study Population
Overall Study STARTED	684815
Overall Study COMPLETED	684815
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study Population n=684815 Participants
Age, Customized <55	0 Participants n=5 Participants
Age, Customized ≥55	684815 Participants n=5 Participants
Sex: Female, Male Female	684815 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Exposure to study drug at least 720 days before disease onset

Population: Case-Cohort analysis population came from the Overall Study Population and comprised 929 women with esophageal cancer (cases) and a Comparison Sample of 338,911 matched control women. Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs.

To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.

Outcome measures

Outcome measures
Measure	Esophageal Cancer Cohort n=929 Participants Participants with any GPRD Medical Code for esophageal cancer (cases).	Comparison Sample (Case Cohort) n=338911 Participants Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes.	Etidronate Participants who initiated osteoporosis treatment with etidronate	Ibandronate Participants who initiated osteoporosis treatment with ibandronate	Risendronate Participants who initiated osteoporosis treatment with risedronate	Raloxifene Participants who initiated osteoporosis treatment with raloxifene
Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) Risedronate	2.6 Percentage of participants	0.9 Percentage of participants	—	—	—	—
Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) Raloxifene	0.3 Percentage of participants	0.4 Percentage of participants	—	—	—	—
Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) Alendronate	4.6 Percentage of participants	2.7 Percentage of participants	—	—	—	—
Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) Etidronate	3.7 Percentage of participants	2.1 Percentage of participants	—	—	—	—
Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) Ibandronate	0.3 Percentage of participants	0.03 Percentage of participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to approximately 7.3 years of follow-up

Population: Inception Cohort came from the Overall Study Population beginning treatment with an osteoporosis study drug (initiators, 78,630 women) and 300,610 matched control women, who did not receive study drug (noninitiators). Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs.

To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used.

Outcome measures

Outcome measures
Measure	Esophageal Cancer Cohort n=300610 Participants Participants with any GPRD Medical Code for esophageal cancer (cases).	Comparison Sample (Case Cohort) n=48377 Participants Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes.	Etidronate n=7851 Participants Participants who initiated osteoporosis treatment with etidronate	Ibandronate n=3941 Participants Participants who initiated osteoporosis treatment with ibandronate	Risendronate n=15655 Participants Participants who initiated osteoporosis treatment with risedronate	Raloxifene n=2806 Participants Participants who initiated osteoporosis treatment with raloxifene
Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis)	32 Number of cases per 100,0000 woman-years Interval 0.5 to 1.6	32 Number of cases per 100,0000 woman-years Interval 0.6 to 2.0	42 Number of cases per 100,0000 woman-years	46 Number of cases per 100,0000 woman-years Interval 0.4 to 2.5	47 Number of cases per 100,0000 woman-years Interval 0.2 to 3.9	29 Number of cases per 100,0000 woman-years

Adverse Events

Overall Study Population

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place