Trastuzumab-dkst Matches Herceptin's Safety, Well-Being for HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer who were treated with biosimilar trastuzumab-dkst (Ogivri) experienced equivalent symptoms, adverse events (AEs), and well-being as patients treated with the originator trastuzumab (Herceptin), according to the results of a study published in JMIR Cancer.¹

Oncology care has benefitted significantly from biosimilars and their reference products, and these agents account for approximately 70% of the growth in costs of drugs from 2010 to 2015. Biosimilars are one way to reduce costs without affecting quality of care.

The study provided an enhanced assessment of electronic patient-reported outcomes (ePROs) that identified undetected symptoms while improving symptom management for patients with various cancer subtypes. The system has suggested improvements in well-being and awareness of AEs between outpatient visits.

The ePRO application collects patient-reported information in clinical trials, including symptoms, quality of life, treatment adherence, and treatment satisfaction. Data is accurately reported in real time and offers informed decisions when analyzing the efficacy and safety of medical interventions. The technological application allows patients to report their treatment results without the limitations of paper-based methods, with valuable insights delivered more efficiently and accurately.²

There is limited research on the real-world outcomes, tolerability, and quality of life that has been performed using ePRO data collected from patients treated with anti-HER2 biosimilars.¹

An observational study was conducted to investigate the daily functional activity, symptoms, and therapy AEs recorded with medidux smartphone application in patients undergoing trastuzumab-dkst therapy.

In December 2017, trastuzumab-dkst was approved by the FDA as the first trastuzumab biosimilar for treatment of HER2-overexpressing breast or metastatic stomach cancer.³ Some patients experienced AEs such as fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain.⁴

Over a 20-month duration, a noninterventional, multicenter, prospective, observational study was held across 5 study sites in Switzerland.¹

The study enrolled patients who received an anti-HER2 treatment regimen. This regimen included an initial intravenous dose of trastuzumab-dkst at 8 mg/kg body weight, followed by maintenance doses of 6 mg/kg. The treatment could be given with or without pertuzumab, chemotherapy, and/or hormone therapy, depending on whether it was administered in a neoadjuvant (pre-surgery) or palliative (symptom management) setting.

The medidux app is a patient-centered, therapy assistance application that supports the structured, standardized, and dynamic documentation of symptoms and therapy AEs. Patients received the app and were instructed to record their symptoms, well-being, EQ-5D-5L questionnaires, cognitive capabilities, and vital parameters every day. Regular study visits were scheduled on days 1, 21, and 42 during 3 weekly chemotherapeutic interventions.

Each patient had an observational period that lasted 6 weeks and at the end, patients decided whether to continue therapy with trastuzumab-dkst or the originator trastuzumab.

The study had a primary objective to evaluate ePRO data received in the medidux app by patients with HER2-positive breast cancer treated with trastuzumab-dkst while comparing the data with ePRO findings obtained from a historical cohort treated with trastuzumab in 2 previous studies (NCT02004496 and NCT03578731).

The well-being of patients in both cohorts and the electronically reported symptoms was considered the secondary objective.

A total of 53 patients who identify as female were enrolled in the study with an average age of 57 years in the prospective cohort and 51 in the historical cohort. Around 38.9% of patients had tumor stage 2 with fewer patients (22.2%) had palliative treatment than neoadjuvant or adjuvant treatment. Over half of the population received dual anti-HER2 blockade with trastuzumab and pertuzumab (59.3%).

ePRO Data

Patients in the prospective cohort experienced 84 of the 92 available different symptoms entered in the app, with the average being more than 4 symptoms a day, that resulted in a total of 9680 symptoms.

There were 54 of the 82 different symptoms found in the historical cohort, with the average being more than 3 symptoms a day, that resulted in 6904 symptom entries.

Common symptoms included fatigue, taste disorder, nausea, diarrhea, dry mucosa, joint discomfort, tingling, sleep disorder, headache, and appetite loss. Most patients in the trastuzumab-dkst cohort experienced minimal (grade 0) and mild (grade 1) toxicities, followed by grade 2, 3, and 4 toxicities.

Common Terminology Criteria for Adverse Events (CTCAE) Score

The primary end point was evaluated among 50 patients who received trastuzumab-dkst and 38 patients treated with the originator trastuzumab.

The average CTCAE scores could be compared between the 2 cohorts with an estimated difference of –1.27 (95% CI, –7.24 to 4.70; P = .68). Notably, the adjusted average of CTCAE scores were not altered between cohorts either (2.51; 95% CI, –3.27 to 8.29).

Well-Being Score

Secondary end points were analyzed in 52 patients who received trastuzumab-dkst and 38 patients as part of the historical cohort. On average, the difference in well-being patients treated with trastuzumab-dkst and originator trastuzumab was 4.45 (95% CI, –3.53 to 12.44; P = .28). There were no major differences between the adjusted well-being scores (3.78; 95% CI, –4.64 to 12.19) of both groups.

Cognitive Abilities in the Prospective Cohort

Data from 37 patients (70%) who performed at least 1 cognitive test were involved in the analysis, with 767 cognitive tests entered overall. The average execution time was 42.9 seconds. However, the small sample size and limited number of cognitive tests recorded were not correlated to the cognitive abilities and treatment performed.

Limitations

The study design limited the results because it neglected a prospective control group and could not be randomized. Additionally, the app was not skilled to perform questionnaires to patients and cognitive abilities were not available for the historical cohort.

Future studies are necessary to analyze data through a randomized design with real-world functions in patients with HER2-positive breast cancer who were treated with anti-HER2 biosimilars.

Ultimately, treatments of both trastuzumab-dkst and the originator expressed equal symptoms, AEs, and well-being as reported by ePRO. Results highlighted the integration of an ePRO tool into research and clinical practice can provide reliable information when investigating tolerability and safety outcomes of similar therapeutic compounds.

References

1. Trojan A, Roth S, Atassi Z, et al. Comparison of the real-world reporting of symptoms and well-being for the HER2-directed trastuzumab biosimilar ogivri with registry data for herceptin in the treatment of breast cancer: Prospective observational study (OGIPRO) of electronic patient-reported outcomes. JMIR Cancer. 2024;10:e54178. doi:10.2196/54178

2. The ultimate guide to ePRO: Everything you need to know. Lindus Health. Accessed July 1, 2024. https://www.lindushealth.com/blog/the-ultimate-guide-to-epro#:~:text=Defining%20ePRO%3A%20What%20It%20Is%20and%20Its%20Importance&text=In%20simple%20terms%2C%20ePRO%20involves

3. FDA approves Ogivri as a biosimilar to Herceptin. News release. FDA. December 1, 2017. Accessed July 2, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ogivri-biosimilar-herceptin#:~:text=On%20December%201%2C%202017%2C%20the,gastric%20or%20gastroesophageal%20junction%20adenocarcinoma).

4. OGIVRI (trastuzumab-dkst). Ogivri. Accessed July 2, 2024. https://www.ogivri.com/