Purpose: The purpose of this study was to evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip)-based chemotherapy in breast cancer.
Methods: Medical charts of patients with breast cancer, who were treated and followed up with NDLS (75– 100 mg/m²; 3-week cycle)-based chemotherapy from August 2014 to September 2018, were analyzed in this multicenter, retrospective study. The study endpoints were overall response rate (ORR: complete response [CR]+partial response [PR]) and disease control rate (DCR: CR+PR+stable disease [SD]) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings.
Results: Of 91 patients (neoadjuvant: 12, adjuvant: 61, metastatic: 18), efficacy evaluation in 29 patients (neoadjuvant: 12/12, metastatic: 17/18) demonstrated an ORR and DCR of 100%, respectively, in the neoadjuvant setting, and an ORR of 64.7% and DCR of 70.6%, respectively, in the metastatic setting. At a median follow-up of 21.6 months (range: 2.1 to 49.9 months), median OS was not reached in neoadjuvant and adjuvant settings, and it was 30.4 months in metastatic settings. At least one adverse event (AE) was reported in 59.3% of patients. Anemia, thrombocytopenia, lymphopenia, and neutropenia were the most common hematological AEs reported while hyperglycemia and alteration in liver function tests were the most common non-hematological AEs. NDLS-based treatment was well tolerated without any new safety concerns.
Conclusion: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of breast cancer. Further, NDLS is being evaluated prospectively in patients with triple-negative breast cancer (ClinicalTrials.gov: NCT03671044).

Keywords: DoceAqualip, NDLS, nanosomal docetaxel lipid suspension, breast cancer

INTRODUCTION

Breast cancer is one of the most common cancers globally.¹ In women, breast cancer is the most commonly diagnosed cancer and a leading cause of cancer mortality worldwide.² As per the GLOBOCAN 2018 report, breast cancer accounts for 11.6% of all cancer cases with 2,088,849 new cases and 626,679 (6.6%) deaths reported globally. In India, breast cancer has an incidence of 27.7% (n=162,468) among all cancers in women.²^,3

Docetaxel has emerged as the agent of choice with established efficacy and tolerability in the treatment of breast cancer.⁴ Docetaxel is approved for the treatment of locally advanced or metastatic breast cancer (MBC) and for adjuvant treatment of operable node-positive breast cancer.⁵ Docetaxel has also demonstrated efficacy and tolerability in the neoadjuvant treatment of operable breast cancer.⁶^,7

The conventional formulation of docetaxel has several toxicity issues related to its excipients, polysorbate 80 and ethanol, such as acute hypersensitivity reactions,⁸^,9 cumulative fluid retention,¹⁰ peripheral neuropathy,¹¹ severe anaphylactoid reactions,¹² infusion-site reactions,¹³ and alcohol intoxication.¹⁴^,15 Corticosteroids and antihistamines are used as premedication to overcome these toxicities,¹⁶^–18 but these adverse effects may still occur in some patients.¹⁹ A novel lipid based, polysorbate 80 and ethanol free formulation of docetaxel, nanosomal docetaxel lipid suspension (NDLS, DoceAqualip, of Intas Pharmaceuticals Limited, India), was developed to overcome these toxicity issues.²⁰ NDLS has shown comparable efficacy and tolerability to conventional docetaxel in the treatment of MBC in a prospective study.²⁰ NDLS has also demonstrated efficacy and safety for the management of breast cancer in previous retrospective studies.²¹^,22 The current report presents a multicenter, retrospective experience in real-world practice evaluating the efficacy and safety of NDLS-based chemotherapy in the treatment of breast cancer.

METHODS

Study Design

In our multicenter, observational, retrospective study, medical charts of women with breast cancer, who were treated with NDLS-based chemotherapy as part of their routine clinical care at four centers across India, were analyzed. The study endpoints were overall response rate (ORR: proportion of patients achieving complete [CR]+partial response [PR]), disease control rate (DCR: CR+PR+stable disease [SD]) and overall survival (OS, defined as time from treatment to death due to any cause; for patients who were still alive at the time of data analysis or who were lost to follow-up, OS was censored at the last recorded date that the patient was known to be alive). ORR and DCR were analyzed for patients who received NDLS-based treatment in neoadjuvant and metastatic settings, and OS was evaluated for all patients. Treatment response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.²³ Incidence of adverse events (AEs) documented in the treatment charts were recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Criteria version 5.²⁴ Similarly, data on death and discontinuations were captured from patients’ health records.

Ethics Statement

The study protocol was reviewed and approved by OM ethics committee, Ahmedabad, India. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and in accordance with the International Conference on Harmonization’s Good Clinical Practice guidelines, applicable regulatory requirements, and in compliance with the protocol. Patient consent to review their medical records was not required by the committee as NDLS is already approved in India and patient confidentiality was completely maintained. In this retrospective study, no patient identifiers were used and data were anonymized.

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