HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug. Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the DATROWAY Prescribing Information all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information). Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
DATROWAY® (datopotamab deruxtecan-dlnk)
(DAT-roe-way)
Daiichi Sankyo, Inc.
Approval date: January 17, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
DATROWAY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate used to treat adults who have hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer:
- that cannot be removed by surgery (unresectable) or has spread to other parts of the body (metastatic), and
- who have received prior endocrine-based therapy and chemotherapy treatment for unresectable or metastatic disease.
How is this drug used?
DATROWAY is given into your vein through an intravenous (IV) infusion once every three weeks.
Who participated in the clinical trials?
The FDA approved DATROWAY based primarily on safety and efficacy evidence from one clinical trial (TROPION-Breast01; NCT05104866) of 732 patients with unresectable or metastatic HR-positive, HER2-negative breast cancer. The trial was conducted at 166 sites in 20 countries across North and South America, Eastern and Western Europe, South Africa, and Asia.
There were 59 patients enrolled in the United States, 34 in the DATROWAY arm and 25 in the investigator’s choice of chemotherapy arm. The remaining 673 patients (92%) were enrolled outside the United States.
How were the trials designed?
The benefits and side effects of DATROWAY were evaluated in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer who had been previously treated with endocrine-based therapy and chemotherapy. Patients were randomly assigned to receive DATROWAY by IV infusion every 3 weeks or chemotherapy until their disease worsened or the side effects became too toxic.
The benefit of DATROWAY was measured by the length of time to cancer worsening or death (progression-free survival [PFS]) and the length of time patients lived (overall survival [OS]). The trial also measured how many patients experience cancer shrinkage (objective response rate [ORR]) and how long that shrinkage lasted (duration of response [DOR]). The trial also provided information about the drug’s side effects.
How were the trials designed?
DATROWAY was evaluated in TROPION-Breast01, a multicenter, open-label, randomized trial of 732 patients with unresectable or metastatic HR-positive, HER2-negative breast cancer who had been treated with one or two prior lines of systemic chemotherapy in the unresectable or metastatic disease setting. Patients must have also experienced disease progression on and deemed not suitable for further endocrine therapy. Patients could not enroll if they had a history of interstitial lung disease (ILD) or pneumonitis requiring treatment with steroids, had ongoing ILD or pneumonitis, or had clinically significant corneal disease.
Patients received either DATROWAY 6mg/kg (n=365) by intravenous infusion every 3 weeks or investigator’s choice of chemotherapy (n=367) until disease progression or unacceptable toxicity. The choice of chemotherapy was determined by the investigator from one of the following options: eribulin, capecitabine, vinorelbine, or gemcitabine.
The major efficacy outcomes were PFS as assessed by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and OS. Additional efficacy outcomes included confirmed ORR and DOR by BICR.
DEMOGRAPHICS SNAPSHOT
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Multidisciplinary Review
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Multidisciplinary Review
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Multidisciplinary Review
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Multidisciplinary Review
Who participated in the trials?
Table 1. Baseline Demographics by Age, Race, Sex, and Ethnicity
| Demographics | DATROWAY (n=365) |
Chemotherapy (n=367) |
Total (n=732) |
|---|---|---|---|
| Sex | |||
| Female | 360 (98.6%) | 363 (98.9%) | 723 (98.8%) |
| Male | 5 (1.4%) | 4 (1.1%) | 9 (1.2%) |
| Race | |||
| Black or African American | 4 (1.1%) | 7 (1.9%) | 11 (1.5%) |
| Asian | 146 (40.0%) | 152 (41.4%) | 298 (40.7%) |
| White | 180 (49.3%) | 170 (46.3%) | 350 (47.8%) |
| Other | 3 (0.8%) | 6 (1.6%) | 9 (1.2%) |
| Not reported | 32 (8.8%) | 32 (8.7%) | 64 (8.7%) |
| Age | |||
| <65 | 274 (75.1%) | 295 (80.4%) | 569 (77.7%) |
| >=65 | 91 (24.9%) | 72 (19.6%) | 163 (22.3%) |
| Ethnicity | |||
| Hispanic or Latino | 40 (11.0%) | 43 (11.7%) | 83 (11.3%) |
| Not Hispanic or Latino | 322 (88.2%) | 318 (86.6%) | 640 (87.4%) |
| Missing | 3 (0.8%) | 6 (1.6%) | 9 (1.2%) |
Source: Adapted from FDA Review
What are the benefits of this drug?
The time patients lived without their cancer worsening (PFS) was longer for those who received DATROWAY compared to those who received chemotherapy. Patients in the DATROWAY group had a median time to cancer worsening of 6.9 months compared to 4.9 months for patients in the chemotherapy group.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Summary of Efficacy in TROPION-Breast01, Efficacy Population
| Efficacy Parameter | DATROWAY (n=365) |
Chemotherapy (n=367) |
|---|---|---|
| Duration of Responsea | ||
| Progression-Free Survival a | ||
| Number of events (%) | 212 (58) | 235 (64) |
| Progressive Disease | 201 (55) | 218 (59) |
| Death | 11 (3) | 17 (5) |
| Median, months (95% CI) | 6.9 (5.7, 7.4) | 4.9 (4.2, 5.5) |
| Hazard ratio (95% CI) b | 0.63 (0.52, 0.76) | |
| p-value c, d | < 0.0001 | |
| Overall Survival | ||
| Number of events (%) | 223 (61) | 213 (58) |
| Median, months (95% CI) | 18.6 (17.3, 20.1) | 18.3 (17.3, 20.5) |
| Hazard ratio (95% CI) b | 1.01 (0.83, 1.22) | |
| p-value c | NS | |
| Confirmed Objective Response Rate a | ||
| n (%) | 133 (36) | 84 (23) |
| (95% CI) | 31, 42 | 19, 28 |
| Complete Response n (%) | 2 (0.5) | 0 |
| Partial Response n (%) | 131 (36) | 84 (23) |
| Median, months (95% CI) | 6.7 (5.6, 9.8) | 5.7 (4.9, 6.8) |
CI: Confidence interval; NS: not statistically significant
a Assessed by blinded independent central review (BICR)
b Based on the stratified Cox proportional hazards model
c Two-sided p-value based on stratified log-rank test.
d p-value is compared with the allocated alpha of 0.01
Source: DATROWAY Prescribing Information Section 14.1
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity?
- Sex: Breast cancer is rare in males, and DATROWAY was only tested in a few male patients. There was not enough information to assess whether the benefit of DATROWAY differs by sex. However, there was no biological rationale for a differential effect for DATROWAY based on sex.
- Race: The majority of patients were White or Asian. DATROWAY worked similarly in White and Asian patients. The number of patients of other races were limited; therefore, it could not be determined whether there were differences in how DATROWAY worked among other races.
- Age: DATROWAY worked similarly in patients younger than 65 years of age and patients 65 years and older.
- Ethnicity: The majority of patients were not Hispanic or Latino. The number of patients who were Hispanic or Latino was limited; therefore, it could not be determined whether there were differences in how DATROWAY worked in patients based on ethnicity.
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity groups?
Table 3 summarizes PFS results by Sex, Race, Age, and Ethnicity. These analyses were exploratory and therefore should be interpreted with caution.
Table 3. Efficacy Results by Sex, Race, Age, and Ethnicity, Efficacy Population
| DATROWAY | Chemotherapy | |
|---|---|---|
| Progression Free Survival (PFS) | ||
| By Sex | ||
| Female | ||
| Number of patients | 360 | 363 |
| Number of events (%) | 210 (58) | 231 (64) |
| Median PFS (95% CI), in months | 6.8 (5.6, 7.2) | 4.9 (4.2, 5.5) |
| Hazard ratio (95% CI)b | 0.65 (0.54, 0.78) | |
| Male | ||
| Number of patients | 5 | 4 |
| Number of events (%) | 2 (40) | 4 (100) |
| Median PFS (95% CI), in months | 9.7 (4.2, NE) | 2.9 (1.2, NE) |
| Hazard ratio (95% CI)b | NC (NC, NC) | |
| By Race | ||
| Asian | ||
| Number of patients | 146 | 152 |
| Number of events (%) | 88 (60) | 101 (66) |
| Median PFS (95% CI), in months | 5.6 (5.4, 7.6) | 4.4 (4.0, 5.6) |
| Hazard ratio (95% CI)b | 0.70 (0.52, 0.93) | |
| White | ||
| Number of patients | 180 | 170 |
| Number of events (%) | 105 (58) | 109 (64) |
| Median PFS (95% CI), in months | 6.9 (5.7, 8.3) | 4.4 (4.2, 5.5) |
| Hazard ratio (95% CI)b | 0.60 (0.46, 0.79) | |
| By Age | ||
| <65 years | ||
| Number of patients | 274 | 295 |
| Number of events (%) | 163 (59) | 190 (64) |
| Median PFS (95% CI), in months | 5.7 (5.5, 7.1) | 4.4 (4.1, 5.4) |
| Hazard ratio (95% CI)b | 0.64 (0.52, 0.79) | |
| ≥65 years | ||
| Number of patients | 91 | 72 |
| Number of events (%) | 49 (54) | 45 (63) |
| Median PFS (95% CI), in months | 8.3 (6.6, 9.6) | 6.9 (5.3, 8.1) |
| Hazard ratio (95% CI)b | 0.65 (0.43, 0.97) | |
| By Ethnicity | ||
| Hispanic or Latino | ||
| Number of patients | 40 | 43 |
| Number of events (%) | 18 (45) | 27 (63) |
| Median PFS (95% CI), in months | NE (4.1, NE) | 5.5 (4.2, 5.9) |
| Hazard ratio (95% CI)b | 0.50 (0.27, 0.91) | |
| Not Hispanic or Latino | ||
| Number of patients | 322 | 318 |
| Number of events (%) | 192 (60) | 207 (65) |
| Median PFS (95% CI), in months | 6.8 (5.6, 7.2) | 4.4 (4.2, 5.5) |
| Hazard ratio (95% CI)b | 0.64 (0.53, 0.78) |
a. Assessed by BICR
b. Based on the unstratified Cox proportional hazards model
NE= not estimable; NC= not calculable
Source: FDA Multidisciplinary Review
What are the possible side effects?
DATROWAY carries Warnings and Precautions for lung problems that may be severe, life-threatening, or that may lead to death, eye problems, mouth ulcers and sores, and harm to your unborn baby.
The most common side effects were mouth ulcers and sores, nausea, tiredness, decreased white blood cell counts decreased calcium, hair loss, decreased red blood cell counts, constipation, dry eye, vomiting, increased blood levels of liver enzymes, and an eye problem called keratitis.
The possible side effects occurring in ≥10% of patients treated with DATROWAY are listed in Table 4.
Table 4: Adverse Reactions Occurring in ≥10% Patients (Safety Population)
| Adverse Reactions | DATROWAY N=360 |
Chemotherapy N=351 |
||
|---|---|---|---|---|
| All Grades % |
Grades 3 or 4 % |
All Grades % |
Grades 3 or 4 % |
|
| Gastrointestinal Disorders | ||||
| Stomatitis a | 59 | 7 | 17 | 2.6 |
| Nausea | 56 | 1.4 | 27 | 0.6 |
| Constipation | 34 | 0.3 | 17 | 0 |
| Vomiting | 24 | 1.1 | 12 | 1.1 |
| Diarrhea | 11 | 0.6 | 19 | 1.4 |
| Abdominal pain a | 11 | 0.6 | 15 | 1.4 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue b | 44 | 4.2 | 40 | 3.7 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Alopecia | 38 | 0 | 22 | 0 |
| Rash a | 19 | 0 | 17 | 2.3 |
| Eye Disorders | ||||
| Dry eye | 27 | 0.8 | 13 | 0 |
| Keratitis c | 24 | 1.1 | 10 | 0 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetite | 16 | 1.4 | 16 | 0.9 |
| Infections and Infestations | ||||
| COVID-19 a | 16 | 1.4 | 13 | 0.9 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||||
| Cough a | 15 | 0 | 10 | 0 |
Events were graded using NCI CTCAE v5.0.
a Includes other related terms.
b Includes fatigue, asthenia, lethargy, malaise
c Includes corneal disorder, corneal erosion, corneal infiltrates, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, and ulcerative keratitis
Source: FDA Multidisciplinary Review
Were there any differences in side effects among sex, race, age, and ethnicity?
- Sex: Breast cancer is rare in males, and DATROWAY was only tested in a few male patients. There was not enough information to assess whether the safety of DATROWAY differs by sex.
- Race: The safety of DATROWAY in White and Asian patients was generally similar. Differences in side effects among Black or African American patients or patients of other races could not be determined due to small number of these patients treated with DATROWAY.
- Age: Serious side effects was more common in patients 65 years and older compared to younger patients; however, no other differences in safety were observed patients 65 years and older compared to younger patients.
- Ethnicity: Differences in safety of DATROWAY in Hispanic or Latino and non-Hispanic or Latino patients could not be determined due to the number of Hispanic or Latino patients.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Analysis of side effects by sex, race, and ethnicity were limited because almost all patients were female, White or Asian, and not Hispanic or Latino. Table 5 summarize adverse events by age.
Table 5. Subgroup Analysis of Adverse Events by Age (Safety Population)
| Adverse Reactions | DATROWAY N=360 |
|
|---|---|---|
| <65 (n=269) n (%) |
≥65 (n=91) n (%) |
|
| Any grade event | 260 (97) | 90 (99) |
| Grade ≥3 event | 80 (30) | 37 (41) |
| Any SAE | 36 (13) | 18 (20) |
Source: FDA Multidisciplinary Review
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
