Christie J. Hilton, DO, assistant professor, Department of Medicine, Drexel University College of Medicine, director, Academic Breast Oncology, Allegheny Health Network (AHN), AHN Cancer Institute, discusses the first-line standard of care (SOC) and changes in the second-line SOC, including key findings from the phase 3 DESTINY-Breast03 trial (NCT03529110), in patients with HER2-positive metastatic breast cancer.

In the first-line setting, patients with HER2-positive metastatic breast cancer should receive a taxane plus trastuzumab (Herceptin) and pertuzumab (Perjeta), a regimen that has remained standard, Hilton says. However, the most effective second-line treatment for patients with HER2-positive metastatic breast cancer has evolved from ado-trastuzumab emtansine (Kadcyla) to fam-trastuzumab deruxtecan-nxki (Enhertu), Hilton explains.

The randomized, open-label, multicenter DESTINY-Breast03 trial investigated the efficacy and safety of trastuzumab deruxtecan compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. At a median follow-up of 28.4 months in the trastuzumab deruxtecan arm and 26.5 months in the trastuzumab emtansine arm, the median progression-free survival (PFS) was 28.8 months in patients who received trastuzumab deruxtecan vs 6.8 months in those who received trastuzumab emtansine. In addition, the median overall survival (OS) was not reached (NR) with 72 OS events vs NR with 97 OS events in the trastuzumab deruxtecan and trastuzumab emtansine arms, respectively. The safety profile was similar between the 2 arms, with 56% and 52% of patients in the trastuzumab deruxtecan and trastuzumab emtansine arms, respectively, experiencing adverse effects of grade 3 or higher. Notably, interstitial lung disease occurred in 15% of patients who received trastuzumab deruxtecan vs 3% of those who received trastuzumab emtansine.

The PFS benefit with trastuzumab deruxtecan in this trial supports the use of this agent as the new second-line SOC in HER2-positive metastatic breast cancer, Hilton emphasizes. However, trastuzumab emtansine may still play a role in the treatment of patients with this disease, Hilton concludes.

Videos

Christie J. Hilton, DO, discusses the first-line standard of care and changes in the second-line SOC, including key findings from the phase 3 DESTINY-Breast03 trial, in patients with HER2-positive metastatic breast cancer.

Dr Hilton on Trastuzumab Deruxtecan in HER2+ Metastatic Breast Cancer

Christie J. Hilton, DO, assistant professor, Department of Medicine, Drexel University College of Medicine, director, Academic Breast Oncology, Allegheny Health Network (AHN), AHN Cancer Institute, discusses the potential impact of the ongoing phase 2 CompassHER2-pCR trial (NCT04266249) for patients with HER2-positive breast cancer.

The study is evaluating the de-escalation of further chemotherapy for patients with stage II/IIIa HER2-positive breast cancer who achieve a pathologic complete response (pCR) following surgery. All enrolled patients are receiving 4 cycles of neoadjuvant chemotherapy consisting of paclitaxel, nab-paclitaxel (Abraxane), or docetaxel in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta). Patients who experience a pCR are proceeding to arm A, where they are receiving adjuvant trastuzumab plus pertuzumab for up to 13 cycles, with radiation and hormone therapy allowed, if appropriate. Patients with residual invasive disease following surgery are being given standard-of-care ado-trastuzumab emtansine (T-DM1; Kadcyla) for 14 doses with the option for chemotherapy and hormone therapy, if appropriate.

Although data have yet to read out from the study, findings could help lead to a better understanding of which patients could be candidates for de-escalated adjuvant chemotherapy, Hilton notes. This approach allows for patients who achieve a pCR to receive only 1 chemotherapy in the neoadjuvant setting before continuing targeted therapy after surgery, Hilton adds.

The results of this trial are highly anticipated and have the potential to deliver impactful results for patients with HER2-positive breast cancer, Hilton continues. Although it could be difficult to find the exact balance to know when de-escalating therapy is appropriate, CompassHER2-pCR could serve as another step toward creating response-guided therapy for patients with HER2-positive breast cancer, Hilton concludes.

Christie J. Hilton, DO, discusses the potential impact of the ongoing phase 2 CompassHER2-pCR trial for patients with HER2-positive breast cancer.


Dr Hilton on the Potential Impact of the CompassHER2-pCR Trial in HER2+ Breast Cancer

Christie J. Hilton, DO, assistant professor, Department of Medicine, Drexel University College of Medicine, director, Academic Breast Oncology, Allegheny Health Network (AHN), AHN Cancer Institute, discusses the impact of fam-trastuzumab deruxtecan-nxki (Enhertu) on the treatment of patients with HER2-positive metastatic breast cancer and ongoing research with the agent in this patient population.

Although the standard-of-care first-line regimen of the combination of trastuzumab (Herceptin), pertuzumab (Perjeta), and chemotherapy has remained largely unchanged, other developments have altered the treatment landscape in later lines for patients with HER2-positive metastatic breast cancer, Hilton says.

In the second-line setting, trastuzumab deruxtecan has replaced ado-trastuzumab emtansine (T-DM1; Kadcyla) as the standard of care, Hilton expands. In the phase 3 DESTINY-Breast03 trial (NCT03529110), which supported the FDA approval of trastuzumab deruxtecan in this setting, trastuzumab deruxtecan elicited significant improvements in progression-free survival compared with T-DM1. Based on these findings, trastuzumab deruxtecan became the new standard of care in the second-line setting; however, T-DM1 still has a role in the treatment armamentarium, Hilton notes.

Ongoing and future investigations will continue to explore the use of trastuzumab deruxtecan in additional settings, Hilton continues. The phase 3 DESTINY-Breast05 trial (NCT04622319) is evaluating trastuzumab deruxtecan vs T-DM1 in patients at a high-risk for recurrence who did not achieve a complete response following neoadjuvant treatment. Findings from this study could increase understanding of whether this approach could improve outcomes for patients with residual disease, Hilton concludes.

Christie J. Hilton, DO, discusses the impact of trastuzumab deruxtecan on the treatment of patients with HER2-positive metastatic breast cancer and ongoing research with the agent in this patient population.

Dr Hilton on the Impact of Trastuzumab Deruxtecan in HER2+ Breast Cancer

	Quality Oncology Practice Initiative (QOPI) is an oncologist-created quality improvement program developed and maintained by ASCO. It is important to be able to objectively review the care that is given in your institution in order to improve the quality of care that is ultimately delivered. The QOPI program creates a uniform measurement of the quality of care delivered by an oncologist; this affords self-examination and directed improvement of practices. QOPI enables self-assessment through twice-yearly retrospective medical chart reviews that are designed to be used in the outpatient hematology/oncology setting. The collection of data from medical records applies identified universal quality measures that have been defined and developed by practicing medical oncologists based on established consensus guidelines. QOPI is designed to objectively measure parameters reflective of quality care that are managed by the medical oncologist. The results of each chart audit allow participants to compare their findings against other participating groups, enabling them to direct their efforts of quality improvement by identifying areas of deficiency.

	There are many benefits to QOPI. At its most basic level, QOPI places an emphasis on documentation. In medicine, we have all been told, “If it is not documented, it didn’t happen.” QOPI also focuses our attention on specifically what is important to include in an oncology patient’s medical record, which is paramount in a fellow’s education. For example, we may know that a particular chemotherapy in a certain case is for palliative intent and we may have discussed it with the patient, but it should be explicitly documented. QOPI also exposes us to continual practice-based quality improvement, which is one of the ACGME core competencies for fellowship. Participation in QOPI satisfies the practice-based improvement component of the ACGME requirements.

What type of information do you obtain from the charts?

	QOPI includes a variety of modules from which to choose. Some modules are universal (Core Measures, End-of-Life Care, and Symptom/ Toxicity Management), and others are disease specific (Breast Cancer, Colorectal Cancer, and NHL). Our fellowship program plans to participate in the Core Measures and Symptom/Toxicity Management modules for the spring 2012 audit. (There are 2 audits each year, in the spring and fall.) These 2 modules contain 34 total data points (25 Core Measures and 9 Symptom/ Toxicity Management measures) to be collected from patient charts. An example of the Core Measures data includes identifying chart documentation of pain assessment: Was the patient’s pain documented and quantified by the second visit? Was a plan documented for the treatment of moderate/ severe pain? If narcotics were prescribed, was the effectiveness documented at the next visit, and was constipation addressed? These questions address 5 of the 25 core measures.

	One or several modules are chosen, and charts are sequestered for audit. It takes approximately 30 to 45 minutes to audit each chart. After the data are collected, they are entered into a Web-based program that is maintained by ASCO. The data (expressed as percent compliance for each measure) can then be reported in a variety of ways. Percent compliance for each measure can be reported by overall practice or broken down to report each individual physician/fellow. The results can then be compared with the overall database results. This allows each program to compare its compliance with results from previous audits in order to gauge its overall improvement, as well as to judge overall performance in comparison with other programs.

How does your program incorporate QOPI for the fellows?

	The Allegheny General Hospital has been using QOPI on the attending level since 2006, and it is being initiated on the fellow level in spring 2012. To prepare for the addition of the program, we have been asked to keep track of at least 10 patients from our continuity clinic to submit for the spring 2012 audit. We were asked to choose our patients based on the following criteria, which are established by ASCO QOPI guidelines: patients must be diagnosed with an invasive malignancy in the past 2 years and must have had 2 office visits in a 6-month-period. Additionally, we were asked to choose patients whom we were involved with directly in development of the treatment plan and its documentation. In spring 2012, we plan to submit our 10 patients for review by another fellow in the program. Charts will not be self-analyzed in an attempt to prevent bias in regard to interpretation of the documentation.

	In preparation of initiation of QOPI, the fellows were involved in auditing charts for the attending-level spring 2011 audit. At that time, each fellow was asked to review 2 charts that had been previously audited by a third party. We were instructed not to interpret the documentation and to record data based directly on what was documented. For quality control, our individual audits were compared with audits previously performed on the same charts by a third party to determine reproducibility of results. When compared, the results were within 2%, which indicated that we were auditing the charts appropriately.

How will we use the results of the audit?

	We plan to meet after the spring 2012 audit to review our results and formulate a plan for improvement based on our discovered deficiencies. We are excited to participate in the spring 2012 audit, and we are interested to see how our fellowship compares with the practice as a whole and to other fellowships regarding these measures of quality. We were left wondering, however, if QOPI truly measures quality of care, or if it simply measures the quality of documentation. Either way, we believe it is a good tool to utilize in fellowship to help prepare us for our careers in hematology oncology.

Articles

The QOPI program creates a uniform measurement of the quality of care delivered by an oncologist; this affords self-examination and directed improvement of practices. 

Christie J. Hilton, DO

Articles

Dr Hilton on Trastuzumab Deruxtecan in HER2+ Metastatic Breast Cancer

Dr Hilton on the Potential Impact of the CompassHER2-pCR Trial in HER2+ Breast Cancer

Dr Hilton on the Impact of Trastuzumab Deruxtecan in HER2+ Breast Cancer

Using QOPI to Improve Quality Within Your Fellowship Program