Lindsay Fischer is the Associate Editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

For this episode of “The Vitals,” we spoke with Patricia Jakel, MN, RN, AOCN, University of California Los Angeles Health, and Elspeth Knill-Selby, a nurse practitioner in breast surgery at Yale University School of Medicine. The 2 experts discuss the rewards of mentorship—from both a providing and receiving perspective, as well as the importance of nurturing young nurses as they transition to acute care.

“I think to be a well-rounded mentor, you have to have a good sense of self and understand yourself—and be able to articulate your feelings in a positive way.”

“I think I look at mentorship as kind of nurturing somebody along the way, and hopefully contributing to their success in what it is that they choose to do. In nursing, sometimes, and in medicine as well, people can kind of ‘eat their young’, so to speak. Therefore, I would look at it as nurturing and trying to create an environment that's not threatening—because certainly when you go in to nursing, and when you go into [an] advanced practice role, it's scary.”

Podcasts

In this episode of “The Vitals,” 2 veteran oncology nurses discuss the value of mentorship—particularly for novice nurses. 

The Value of Nurse Mentorship in Oncology

Fam-trastuzumab deruxtecan-nxki demonstrated superiority over ado-trastuzumab emtansine (Kadcyla; T-DM1) in all subgroups of patients with previously treated HER2-positive metastatic breast cancer enrolled of the phase 3 DESTINY-Breast03 trial (NCT03529110), explained Sara Hurvitz, MD.

As initially reported at the 2021 ESMO Congress, DESTINY-Breast03 improved progression-free survival (PFS) over T-DM1 in patients with previously treated HER2-positive metastatic breast cancer.1 In this subgroup analysis, investigators examined outcomes based on hormone receptor status (positive vs negative), prior pertuzumab (Perjeta) treatment (yes vs no), visceral disease (yes vs no), prior lines of therapy (0-1 vs ≥2), and patients with brain metastases (yes vs no).

“These data indicated the trastuzumab deruxtecan has a consistent PFS benefit compared with T-DM1 after treatment with trastuzumab and taxane. [The drug] yields high ORRs [overall response rates] and shows intriguing intracranial efficacy for patients with stable brain metastases at baseline,” Hurvitz said. “These data do support the use of trastuzumab deruxtecan in the second-line setting and beyond and moving T-DM1 out of that space.”

®, Hurvitz, director of the Breast Cancer Clinical Research Program, co-director of the Santa Monica UCLA Outpatient Hematology/Oncology Practice, and associate professor of medicine in the Division of Hematology/Oncology at the David Geffen School of Medicine at UCLA, discussed the findings from the subgroup analysis of the DESTINY-Breast03 trial, and future research directions for trastuzumab deruxtecan.

®: What was the rationale behind DESTINY-Breast03? Could you provide any background information that will set the stage for the subgroup analyses?

: The DESTINY-Breast03 trial is a study evaluating trastuzumab deruxtecan vs T-DM1. Trastuzumab deruxtecan was evaluated in a single-arm, phase 2 clinical trial in [patients with] heavily pretreated HER2-positive metastatic breast cancer, called the DESTINY-Breast01 study [NCT03248492]. That trial demonstrated significant ORR of over 60% and a long PFS of over 19 months, which is unheard of in patients who had been so heavily pretreated.

Given those promising phase 2, single-arm data, the FDA did approve [trastuzumab deruxtecan] in 2019 for those with heavily pretreated HER2-positive metastatic disease. To date, however, there was no randomized clinical trial, until 2021, comparing trastuzumab deruxtecan to a standard-of-care therapy. At ESMO in 2021, the DESTINY-Breast03 clinical trial was first presented as an interim analysis, [in which] trastuzumab deruxtecan was compared with T-DM1, a different antibody-drug conjugate, in patients who had received at least 1 prior line of trastuzumab (Herceptin)- or taxane-based therapy and had experienced disease progression. It was a phase 3 randomized clinical trial, [and enrolled] over 500 patients. This study was aimed to compare the PFS of the 2 drugs, and to look at overall survival [OS] and several secondary endpoints.

What was evaluated in the subgroup analyses? What was the design and which patients were included?

The PFS was first presented at ESMO 2021. It was demonstrated that trastuzumab deruxtecan was associated with a significant improvement, with a hazard ratio of 0.28, which is almost unheard of. In my memory, I can't remember a hazard ratio like that in breast cancer. The median PFS had not been met for trastuzumab deruxtecan and was approximately 6.8 months for T-DM1.

[Several] questions then came up, [including] whether any subgroups within the trial may benefit from the use of trastuzumab deruxtecan compared with T-DM1. [Therefore], at this analysis, we looked at outcomes based on whether patients had hormone receptor-coexpression of their tumor, whether they had previously received pertuzumab [Perjeta] treatment, whether they had visceral disease, and whether they had received 0 or 1 prior lines of therapy or 2 or more prior lines of therapy. Also, we wanted to look at the population of patients who had stable brain metastases at [baseline]. No matter how you looked at it, trastuzumab deruxtecan was associated with an improved PFS as well as improved ORR in all those subgroups compared with T-DM1.

We then did a deep dive into how trastuzumab deruxtecan worked compared with T-DM1 in patients who had baseline brain metastases. Interestingly, in those patients who had baseline brain metastases, the median PFS with trastuzumab deruxtecan was approximately 15 months vs only 3 months with T-DM1. Moreover, when we looked at what was happening inside the brain for those patients who came on study with brain metastases at baseline, the intracranial ORR associated with trastuzumab deruxtecan was 63%, and with T-DM1 it was only 34%. [As such], the intracranial responses [are] quite dramatic with trastuzumab deruxtecan in this clinical trial, which are notable.

Did you observe anything surprising regarding the safety profile of trastuzumab deruxtecan?

The safety profile looked similar compared [with] what was previously reported at ESMO in 2021. We did do another look at interstitial lung disease [ILD], and the rates of ILD in the non-Asian group vs the Asian group because sometimes [patients who are] Asian will have differing rates of toxicity with agents. In fact, the rates of ILD remained about 10.5% in the overall patient population with no grade 4 or 5 events, and no differences in rates of ILD [in] the Asian vs non-Asian subgroups.

Are there any next steps planned for this drug?

I am excited to see the data from the DESTINY-Breast02 clinical trial [NCT03523585] looking at trastuzumab deruxtecan vs lapatinib (Tykerb) or trastuzumab plus capecitabine, which is a confirmatory trial of DESTINY-Breast01 in more heavily pretreated patients. [I’m] also looking forward to seeing trastuzumab deruxtecan being evaluated in the first-line setting and in patients with active brain metastases.

Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. San Antonio, TX. Abstract GS3-01.

This article was originally published on OncLive as “Trastuzumab Deruxtecan Maintains PFS Benefit Across Subgroups in HER2+ Metastatic Breast Cancer”

Articles

An expert discusses the implications of a subgroup analysis of the DESTINY-BREAST03 trial, which highlighted the efficacy of trastuzumab deruxtecan in HER2-positive metastatic breast cancer. 

Patients With HER2+ Metastatic Breast Cancer Experience Consistent PFS Benefit With Trastuzumab Deruxtecan

Patients with lower-risk myelodysplastic syndromes (MDS) appeared to benefit from receiving a fixed combination or oral decitabine and cedazuridine (Inqovi), according to results from the phase 3 ASCERTAIN trial. Findings on the combination’s efficacy and tolerability were recently presented during the 2021 American Hematology Society Annual Meeting & Exposition.

“Oral [hypomethylating agents] are a game changer for patients with MDS,” said study author James K. McCloskey, MD. “We’ve known this in high-risk disease, but this brings in an orphan patient population where we haven’t had other options previously. The oral nature of this drug is particularly important to consider when we’re talking about low-risk patients.”

®, McCloskey, chief, Leukemia Division, John Theurer Cancer Center, Hackensack Meridian Health, discussed the efficacy of oral decitabine plus cedazuridine, the combination’s potential role in lower-risk MDS, and what this could mean for the patient population.

®: What was the rationale for this study?

: Lower-risk MDS are diseases that we typically treat with a focus around a patient’s cytopenias and attempting to improve the quality of life. We understand these patients may live decades with their disease, but symptoms related to anemia and the impact of transfusion burden and iron overload can impact their outcome.

Unfortunately, outside of luspatercept-aamt [Reblozyl] for ring sideroblastic disease or lenalidomide for patients with 5q-minus associated MDS, we don’t have disease-modifying therapies that are helpful in low-risk disease. By contrast, the hypomethylating agents, including decitabine and azacitidine, are standard in higher-risk MDS where we know they improve overall survival, reduce transfusion requirements, and improve quality of life. [On] occasion, we might use these in low-risk patients, but we have not demonstrated that we improve their overall outcomes with the use of hypomethylating agents in low-risk MDS.

That brings us up to oral decitabine, which is an oral fixed dose of combination decitabine and a CDA inhibitor known as cedazuridine. This was FDA approved based on data from the ASCERTAIN trial, a randomized, crossover study that confirmed equivalent exposure to decitabine when we use this the oral fixed-dose combination compared with parenteral azacytidine. What we’re presenting ASH is an exploration of the patients on the ASCERTAIN trial who had lower-risk disease.

What were the methods that were utilized in the follow-up of this study?

The ASCERTAIN trial was a randomized, crossover study, where patients received 1 cycle of parenteral azacitidine. Then, during the remaining cycles of treatment, they were treated with oral combination therapy.

We obtained PK/PD data to confirm that there was equivalent exposure with the oral and parenteral forms. In this abstract, we're looking at those patients treated on the ASCERTAIN study who had low-risk disease.

Could you share the results that were presented at the meeting?

There were 133 patients in total treated on ASCERTAIN, and 69 patients had lower-risk MDS. The vast majority of those had an intermediate 1 disease, so 93% of these patients. When we look at their treatment, the median number of cycles was 9 but there were patients who received up to 28.

The most common toxicities were ones that might be predictable based on prior experience with hypomethylating agents in general and the previous published data with ASCERTAIN, [which] included cytopenias and infectious complications, including febrile neutropenia and pneumonia.

With that said, the overall response rate was 57%, and that included 23% of patients who achieved a complete response. What we got to see in this abstract was the rate of transfusion independence, which is important in low-risk patients. We saw 48% of those patients who were receiving red cell transfusions became transfusion independent and 67% of patients who were receiving platelet transfusions became platelet and transfusion independent. The trial also looked at median overall survival and leukemia-free survival, and the median survival endpoints for those patients had not been met at 32 months.

We talked about the treatment goal of...improving quality of life. These oral formulations may be an even bigger deal for low-risk patients who are often outside of our clinic, trying to live their life. By offering them an oral therapy, we are giving them the option to be treated at their home, reducing their visits with us, and hopefully, not only reducing infusion times for chemotherapy, but by offering them transfusion independence, they're going to reduce their time in our infusion chairs. That was one of the big points for me in this data…67% of patients coming off platelet transfusions and 48% off red cell transfusions.

This overall survival and leukemia free survival that exceeds 32 months is impressive. It is going to be interesting to see how this data matures [as we continue] to watch this patient population, and certainly, this gives us something to turn to for those patients that many of us might have been managing in clinic. They’re rare patients, but those patients who have isolated thrombocytopenia, more isolated anemia, this is reassuring data that allows us to apply the current FDA-approved label to those patients and offer them a new option.

Across the board there's a lot of excitement about the opportunity to use these oral [hypomethylating agents] as a backbone in combination trials, as well. Those are certainly ongoing, and there's a lot of exciting combinations that can be thought of. It gives us the opportunity in the future to be considering a completely oral regimen for our elderly, unfit patients.

This article was originally published on OncLive as “Oral Decitabine Plus Cedazuridine Combo Shows Promise in Lower-Risk MDS”

Oral decitabine, an oral fixed-dose of combination decitabine and CDA inhibitor cedazuridine, is an FDA-approved therapy for patients with lower-risk myelodysplastic syndromes.

Oral Decitabine and Cedazuridine Holds Potential to Reduce Clinic Visits, Infusion Time for Patients With Lower-Risk MDS

The launch of a novel program out of the Dignity Health Cancer Institute at St. Joseph’s Hospital and Medical Center seeks to help patients with cancer achieve a healthier sexual life both during and after treatment through personalized therapies.

The program will make sexual health resources available for any patients with cancer, regardless of where they received initial treatment. According to the innovators behind the program, nearly 3 out of 4 patients who undergo therapy consequently experience some degree of a sexual health issue. The design of this program is therefore aimed at helping these patients achieve a better sense of normalcy in this area of their lives.

“Sexual health issues in cancer patients are largely overlooked,” Nicole Afuape, MD, advanced gynecologic surgeon and pelvic pain specialist at Dignity Health Cancer Institute at St. Joseph’s Hospital and Medical Center, said in a press release. “However, we are creating a well-rounded clinical program that is focused on identifying and improving these issues to help the overall quality of life for our patients.”

There are several symptoms that may affect patients’ sexual function after they have received cancer treatments, including dyspareunia, penile curvature, low testosterone levels, erectile dysfunction, difficulty controlling bladder or bowels during intercourse, difficulty with premature ejaculation, low libido, struggles with orgasm, and vaginal dryness, tightness, or burning. On top of these physical complications, anxiety or depression surrounding sex, body shame, poor body image, or low self-esteem can also negatively influence patients’ health post-cancer treatments.

Patients who enroll in the program may expect a comprehensive sexual health assessment, followed by a physical exam to evaluate function, as well as potential dysfunction. Following an exam, patients will receive personalized education about sexual health function, dysfunction, and desire and a comprehensive outline of how these concepts might be impacted by chemotherapy, immunotherapy, surgery or radiation therapy. Patients and partners will also receive supportive care from an interdisciplinary team, which includes physical therapists and social workers.

Adverse events associated with sexual health can vary greatly among patients, so services provided will be tailored to each individual based on their assessment findings.

Available services include surgical interventions, including an excision of vaginal cuff, penile implant, pelvic floor muscle injections, and nerve blocks. In addition, hormone replacement and non-hormonal therapy, pelvic floor physical therapy, penile low-intensity shockwave therapy, and penile erection therapy, are available, alongside sexual health education, relaxation, and support.

“Sexual health dysfunction is very common among cancer patients,” added George Kallingal, MD, urologic oncologist at Dignity Health Cancer Institute at St. Joseph’s. “It can have a significant impact on their lives and their loved ones. Our physicians will provide a welcoming, non-judgmental atmosphere for patients and offer treatments to improve intimacy and overall sexual health.”

Dignity health cancer institute at St. Joseph's launches sexual health program. Dignity Health. St. Joseph’s Hospital and Medical Center. News release. January 3, 2022. Accessed January 12, 2022. https://www.dignityhealth.org/arizona/locations/stjosephs/about-us/press-center/press-releases/dignity-health-cancer-institute-at-st--joseph-s-launches-sexual-

Sexual health & healing after cancer. Dignity Health. Accessed January 12, 2022. https://dignityhlth.org/31Sdg3R

Besides education and emotional support, the newly launched program offers personalized services including surgical interventions, hormone replacement therapy, and penile low-intensity shockwave therapy, to help patients heal from their cancer treatments. 

New Program Helps Patients Recover Sexual Lives Following Cancer Treatment

Diet and supplement use may influence the microbiome and subsequent responses to immunotherapy, according to Jennifer McQuade, MD.

McQuade, an assistant professor of medical melanoma oncology at The University of Texas MD Anderson Cancer Center, recently spoke with 

® about recently published study findings, which suggest that high-fiber diets and lower probiotic use may be associated with improved immunotherapy response rates among patients with melanoma.

“We know that the microbiome is actually mostly not genetically determined, but shaped by our environment, and very specifically by things that we consume,” said McQuade. “What we did [was conduct] a cohort study where we asked our patients about diet and supplement use when they were starting immunotherapy, and we were collecting microbiome specimens.”

“We found that patients that were consuming a high-fiber diet were actually significantly more likely to respond to immunotherapy. This is consistent with the fact that the bacteria that have been associated with response are bacteria that have no roles in fiber fermentation.”

“We followed up that finding with preclinical studies,” she concluded. “In mice, we actually found that by doing fiber deprivation, and fiber manipulation, we are able to then change response to cancer immunotherapy. On the flip side, [when] we also looked at probiotic use, we found that 31% of our patients were actually taking over the counter probiotics—and that's probably driven by all of the attention that the microbiome has been getting—but those patients were actually less likely to respond to immunotherapy.”

Videos

An expert from The University of Texas MD Anderson Cancer Center highlights findings demonstrating the impact that diet and probiotics have in immunotherapy responses.

Diet and Probiotics Influence Immunotherapy Responses in Melanoma

Pembrolizumab was associated with the first positive clinical trial outcomes in the adjuvant setting of non–small-cell lung cancer. 

Adjuvant Pembrolizumab Yields Impressive Disease-Free Survival Outcomes in Select Patients With NSCLC

Early detection is key to improving prognosis and achieving better outcomes for patients. 

Addressing the Impact of COVID-19 and Health Disparities on Cancer Screening

Recently presented findings demonstrate that aspacytarabine may represent a viable treatment option for various subsets of patients with acute myeloid leukemia. 

Aspacytarabine May Be Viable Option for Patients with AML Who Are Unfit for Intensive Therapy

New data support increased fiber consumption and decreased probiotic use among patients receiving immunotherapy.

High-Fiber Diets Strengthen Immunotherapy Responses in Patients With Melanoma

Compared with other antibody-drug conjugates, datopotamab deruxtecan was associated with lower rates of neutropenia, pneumonitis, and hematologic toxicity.  

Datopotamab Deruxtecan Demonstrates Manageable Safety Profile in TNBC 

Seasoned oncology nurses share how the COVID-19 pandemic has affected the standard of care at their institution, the consequences of the staffing shortage, and how they believe the oncology community can work together to create a better working environment.

Voices Behind the Mask: Oncology Nurses Speak Out About Their COVID-19 Experiences

A triplet regimen of tucatinib, trastuzumab, and capecitabine helped patients with HER2-positive metastatic breast cancer and brain metastases live longer with reduced disease progression compared with trastuzumab and capecitabine alone. 

Patients With HER2+ Breast Cancer and Brain Metastases Achieve Better OS With Tucatinib Triplet Regimen

The use of PARP inhibitor olaparib in conjunction with temozolomide may be an effective treatment for patients with advanced uterine leiomyosarcoma whose tumors harbor a BRCA-like phenotype. 

Olaparib Plus Temozolomide Induces Promising Response Duration in Uterine Leiomyosarcoma 

Disease-free survival in liver-only metastatic CRC was significantly improved by introducing adjuvant mFOLFOX6 chemotherapy to hepatectomy

Adjuvant mFOLFOX6 Increases Hepatectomy Efficacy, Improves DFS in Liver-Only Metastatic CRC

Patricia Jakel is an advanced practice nurse for the UCLA Santa Monica Solid Oncology Program. In 1997, she received the Advanced Practice Nurse of the Year Award from the ONS Los Angeles Chapter. She is an active member of American Nurses Association, the American Cancer Society, and the Oncology Nursing Society, and her personal research interests include survivorship, adverse event management, and quality-of-life improvement.

Patricia Jakel, MN, RN, AOCN, reflects on the values of nursing Hackathons and encourages Hackathon participation from oncology nurses.

Nursing Hackathons Drive Innovations 

A novel regimen of relatlimab, an LAG-3 inhibitor, plus nivolumab doubled progression-free survival in patients with untreated, advanced melanoma.

Novel Immunotherapy Combination Shows Promise in Metastatic Melanoma

New data support smoking cessation for patients with lung cancer following their diagnosis. 

Smoking Cessation Following Lung Cancer Diagnosis Reduces Cancer Mortality Risk 

Event co-chair, Syma Iqbal, MD, discusses key points from a recent OncLive® Institutional Perspectives in Cancer webinar, which focused on the evolving landscapes in gastrointestinal cancer. 

Immunotherapy Approvals Propel the Future of GI Cancer Treatment 

Nausea and upper GI discomfort are frequently linked with use of the oral SERD.

Oral Elacestrant Requires Patient Education in Metastatic ER+ Breast Cancer 

An expert from Mount Sinai Hospital comments on potential new ruxolitinib combinations to treat patients with myelofibrosis and MPNs. 



Top Medical News

The Value of Nurse Mentorship in Oncology

Patients With HER2+ Metastatic Breast Cancer Experience Consistent PFS Benefit With Trastuzumab Deruxtecan

Oral Decitabine and Cedazuridine Holds Potential to Reduce Clinic Visits, Infusion Time for Patients With Lower-Risk MDS

New Program Helps Patients Recover Sexual Lives Following Cancer Treatment

Diet and Probiotics Influence Immunotherapy Responses in Melanoma

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