Sacituzumab Govitecan Misses PFS End Point in Metastatic Breast Cancer – CancerNetwork

Executive Summary

A report on the international, open-label phase 3 ASCENT-07 clinical trial (NCT05840211) indicates that the primary endpoint was not met. The study evaluated sacituzumab govitecan-hziy against standard chemotherapy in patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who had progressed after endocrine therapy. This research is a direct contribution to the United Nations’ Sustainable Development Goal 3 (SDG 3), which aims to ensure good health and well-being, specifically by addressing premature mortality from non-communicable diseases (NCDs) like cancer. While the trial did not demonstrate a statistically significant improvement in progression-free survival (PFS), the ongoing evaluation of overall survival (OS) continues to inform the global effort to develop more effective cancer treatments.

Advancing SDG 3: Good Health and Well-being Through Cancer Research

The ASCENT-07 Trial’s Objective

The ASCENT-07 study was designed to assess a novel therapeutic agent’s efficacy and safety in a challenging-to-treat patient population. The core objective aligns with SDG 3, Target 3.4, which seeks to reduce premature mortality from NCDs. By investigating new treatment options for locally advanced, inoperable, or metastatic breast cancer, the trial aimed to contribute to improved health outcomes and longevity for patients, a cornerstone of the global health agenda.

Methodology and Trial Design

Patient Population and Enrollment Criteria

The study enrolled 654 patients, focusing on a specific cohort to ensure targeted and relevant findings. Eligibility was determined by the following criteria:

• Documented HR-positive, HER2-negative metastatic breast cancer.
• Prior treatment with endocrine therapy.
• Eligibility for chemotherapy in the locally advanced or metastatic setting.
• ECOG performance status of 0 or 1.
• Adequate organ function.

Intervention and Comparison

Participants were randomly assigned in a 2:1 ratio to one of two treatment arms, a standard design for evaluating new therapies against the current standard of care, which is essential for achieving the SDG 3 goal of providing access to safe and effective medicines.

• Investigational Arm: Sacituzumab govitecan administered intravenously at 10 mg/kg on days 1 and 8 of a 21-day cycle.
• Control Arm: Investigator’s choice of chemotherapy, including capecitabine, paclitaxel, or nab-paclitaxel.

Endpoints and Measurement

The trial’s success was measured against predefined endpoints, crucial for regulatory assessment and clinical adoption.

1. Primary Endpoint: Progression-free survival (PFS) as determined by blinded independent central review (BICR) based on RECIST v1.1 guidelines.
2. Secondary Endpoints: Overall survival (OS), objective response rate, quality of life, and safety.

Key Findings and Implications for Global Health Goals

Primary Endpoint Analysis

The study did not meet its primary endpoint. Treatment with sacituzumab govitecan did not result in a statistically significant improvement in PFS compared to standard chemotherapy. This outcome underscores the complexities in treating this heterogeneous disease and highlights the ongoing challenges in advancing SDG 3 for NCDs.

Secondary Endpoint Observations

At the time of the primary analysis, data for the key secondary endpoint of OS were immature. However, investigators noted an early trend favoring the sacituzumab govitecan arm. In alignment with the long-term objectives of SDG 3, the trial will continue for further evaluation of OS to fully understand the potential impact of the treatment on patient longevity.

Safety Profile

The safety profile of sacituzumab govitecan was consistent with previous studies. No new safety signals were identified in this patient population. Ensuring patient safety is a fundamental aspect of promoting well-being under SDG 3.

Conclusion: The Path Forward in Breast Cancer Treatment

Contextualizing the Results

Despite the ASCENT-07 trial not meeting its primary PFS endpoint, sacituzumab govitecan remains a standard of care for other indications, including pretreated HR-positive, HER2-negative metastatic breast cancer based on the OS benefit shown in the TROPiCS-02 study. This reinforces the importance of targeted research for specific patient subgroups.

Commitment to Ongoing Research and SDG 3

The continuation of the trial to collect mature OS data reflects a commitment to comprehensive scientific inquiry. This dedication to research is vital for making progress toward the targets of SDG 3. Each clinical trial, regardless of its primary outcome, provides critical knowledge that informs future research and contributes to the global effort to combat non-communicable diseases and improve health and well-being for all.

Analysis of Sustainable Development Goals in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

• SDG 3: Good Health and Well-being

  The article’s core subject is a clinical trial for a breast cancer treatment (sacituzumab govitecan). This directly relates to SDG 3, which aims to “ensure healthy lives and promote well-being for all at all ages.” The research into advanced cancer therapies is fundamental to combating non-communicable diseases and improving health outcomes.

• SDG 9: Industry, Innovation, and Infrastructure

  The article discusses a “phase 3 ASCENT-07 study,” which represents a significant investment in scientific research and development by the pharmaceutical industry (Gilead). This aligns with SDG 9’s goal to “build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation,” particularly through enhancing scientific research and technological capabilities.

• SDG 17: Partnerships for the Goals

  The study is described as an “international, open-label phase 3” trial involving a developer (“Gilead”), a principal investigator from a major research institution (“Hope S. Rugo, MD… at City of Hope Comprehensive Cancer Center”), and 654 patients. This collaboration exemplifies a multi-stakeholder partnership between the private sector and the scientific community to advance global health, which is a key aspect of SDG 17.

2. What specific targets under those SDGs can be identified based on the article’s content?

• SDG 3: Good Health and Well-being

  1. Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment. The article focuses on a treatment for “metastatic breast cancer,” a leading non-communicable disease. The trial’s goal of improving “progression-free survival (PFS)” and “overall survival (OS)” directly contributes to reducing premature mortality from cancer.
  2. Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases. The entire article is a report on the research and development process for a new cancer medicine, sacituzumab govitecan, through a large-scale clinical trial (ASCENT-07).

• SDG 9: Industry, Innovation, and Infrastructure

  1. Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries… including… encouraging innovation and substantially increasing… public and private research and development spending. The phase 3 clinical trial is a direct example of private R&D spending by Gilead to enhance scientific research and innovate in the field of oncology.

• SDG 17: Partnerships for the Goals

  1. Target 17.16: Enhance the Global Partnership for Sustainable Development, complemented by multi-stakeholder partnerships that mobilize and share knowledge, expertise, technology and financial resources. The “international” nature of the ASCENT-07 study, involving a pharmaceutical company, medical centers, and investigators, is a clear example of a global, multi-stakeholder partnership sharing knowledge and resources to achieve a common health goal.
  2. Target 17.17: Encourage and promote effective public, public-private and civil society partnerships. The collaboration between the private company (Gilead) and the medical research community (City of Hope Comprehensive Cancer Center and other investigators) is a model of a public-private partnership aimed at advancing medical treatment.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

• For SDG Target 3.4:

  The article explicitly mentions key metrics used to measure the effectiveness of cancer treatments, which serve as direct indicators of progress in reducing mortality.

  • Indicator: Overall Survival (OS): The article states that “Data for the key secondary end point of overall survival (OS) were immature” but that the trial “remains ongoing for further evaluation of OS.” OS is a direct measure of mortality.
  • Indicator: Progression-Free Survival (PFS): The article notes that the trial “did not meet the primary end point of progression-free survival (PFS).” PFS is a standard indicator used in oncology to measure the length of time a patient lives with the disease without it getting worse.

• For SDG Target 3.b & 9.5:

  The article implies indicators related to the scale and focus of research and development efforts.

  • Indicator: Number and Phase of Clinical Trials: The article identifies a specific “international, open-label phase 3 ASCENT-07 study (NCT05840211)” and references another, “the TROPiCS-02 study [NCT03901339].” The existence and execution of such advanced-phase trials are indicators of significant investment and progress in medical R&D.

• For SDG Target 17.16 & 17.17:

  The structure of the research effort itself serves as an indicator of partnership.

  • Indicator: Formation of International, Multi-stakeholder Research Consortia: The description of the study as “international” and involving a private company (“Gilead”), a leading cancer center (“City of Hope Comprehensive Cancer Center”), and a large patient cohort (“654 patients”) indicates the formation of a global, public-private partnership for medical research.

4. Summary Table of SDGs, Targets, and Indicators

Source: cancernetwork.com