GRADE is trying to find out if there is a link between a hormone called GDF-15 and the side effects that people can experience when taking T-DXd.
GDF-15 can be measured in the blood. GDF-15 levels in the blood will go up when the body is stressed under certain conditions, including breast cancer. There is a link between high GDF-15 levels and the nausea and vomiting experienced with "morning sickness" in pregnancy. It has also been shown that GDF-15 levels will go up with the use of other types of chemotherapy that are known to cause nausea and vomiting.
Side effects such as feeling sick (nausea), vomiting and weight loss are common with T-DXd. Sometimes, these can be so severe that treatment needs to be stopped early. The investigators can't predict who will get bad side effects and who will not.
If the investigators can find out if there is a link between GDF-15 and the side effects of T-DXd, they can use this information in future clinical trials.
Participants aged ≥18 years.
Histologically confirmed diagnosis of metastatic/advanced unresectable HER2-positive or HER2-low breast cancer.
Planned to start treatment with T-DXd.
Life expectancy of at least 4 months.
Current active reversible causes of decreased food intake, as determined by the Investigator.
Receiving tube feedings or any kind of parenteral nutrition at the time of enrolment into the study.
Ongoing cachexia attributable to other reasons unrelated to cancer or cancer treatment as determined by the Investigator that may confound interpretation of weight loss due to T-DXd.
Current adherence to a calorie-restricted diet with the intention of weight loss.
Single group
Blood collection for GDF-15
Other interventionBlood samples of 20-30mL (approximately 1-2 tablespoons in total) will be taken 4 times: * Before first treatment with T-DXd * Two times during treatment (after the first and second doses of T-DXd); and * At the end of T-DXd treatment. At each blood collection, participants will be asked about: * T-DXd side effects * Medications prescribe for T-DXd side effects * Weighed to see if their weight changes during treatment. Personal and health information will also be collected from participants: * Date of birth and age, sex, ethnicity, height, weight, and activity levels. * Details about their cancer: diagnosis, type of cancer, other treatments, and pathology results. * Details about any previous pregnancies: how many, and the severity of any nausea or vomiting experienced during these pregnancies. * Details about their best response to treatment with T-DXd. * Details about the reason they stop T-DXd treatment.
Nausea prior to Cycle 3 of T-DXd, graded according to Common Terminology Criteria for Adverse Advents (CTCAE) v5.0.
To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade nausea (CTCAE Grade 2-4) experienced at this timepoint by patients with metastatic/advanced unresectable HER2-positive or HER2-low breast cancer.
Vomiting prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade vomiting (CTCAE Grade 2-4) experienced by patients at this timepoint.
Weight loss (cachexia) prior to Cycle 3 of T-DXd, graded as per CTCAE v5.0.
To investigate if the percentage change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with moderate/high grade cachexia (CTCAE Grade 2-4) experienced by patients at this timepoint.
Percentage change in GDF-15 and its correlation with treatment-related adverse events (TRAEs)
To explore the correlation of the percentage change in levels of GDF-15 with the treatment-related adverse events (CTCAE Grade 2-4). Treatment-related adverse events (TRAEs) are adverse events classified as possibly, probably or definitely related to T-DXd treatment. TRAEs will be graded as per CTCAE v5.0.
Progression-free survival (PFS)
To explore the relationship between baseline levels of GDF-15 and progression-free survival (PFS) on T-DXd
Exploratory: Association of baseline levels of GDF-15 with Treatment Related Adverse Events (TRAEs).
To explore if baseline levels of GDF-15 are associated with the incidence and severity of TRAEs experienced by patients on T-DXd, graded as per CTCAE v5.0.
Exploratory: Longitudinal change in weight after 2 cycles of T-DXd
To explore if the longitudinal change in levels of GDF-15 from baseline to after receiving 2 cycles of T-DXd is associated with trends in weight change. Weight change is measured as a percentage of baseline weight. End-of-treatment is defined as cessation of treatment due to disease progression or treatment toxicity.
Exploratory: Longitudinal change in weight at end-of-treatment
To explore if the longitudinal change in levels of GDF-15 from baseline at end-of-treatment with T-DXd is associated with trends in weight change. Weight change is measured as a percentage of baseline weight.
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