Ipatasertib plus abiraterone (Zytiga) was associated with improved radiographical progression-free survival (PFS) in patients with metastatic castrate-resistance prostate cancer (mCRPC) and PTEN-loss tumors, according to data from the ongoing IPATential150 trial (NCT03072238), published in 

Of note, the same improvement was not statistically significant in the intention-to-treat population. Adverse events (AEs) reflected previously reported safety profiles.

At the median follow-up at 19 months, the median radiographical PFS was 18.5 months (95% CI, 16.3-22.1) in the experimental arm and 16.5 months (95% CI, 13.9-17.0) in the control arm (HR, 0.77; 95% CI, 0.61-0.98; 

 = .034). Median PFS in the intention-to-treat population was 16.6 months in the control group and 19.2 months in the experimental group (HR, 0.84; 95% CI, 0.71-0.99; 

“Overall, our findings confirm that combined AKT and androgen-receptor signaling pathway blockade with ipatasertib plus abiraterone is superior to androgen-receptor signaling pathway blockade alone with abiraterone in patients with mCRPC with PTEN loss, as previously observed in the phase 2 study,” wrote the investigators. “This trial is, to our knowledge, the first to provide comprehensive phase 3 data confirming the role of simultaneous AKT and androgen- receptor signaling pathway inhibition.”

The study included 1611 patients with generally balanced baseline characteristics who were divided equally into investigative and control arms. Roughly 18% of the participants had received prior taxane-based therapy for hormone-sensitive prostate cancer, and 14% had visceral metastases, including lung, liver, or a combination of both. The participants consisted of 561 (51%) European patients, 277 (25%) Asian-Pacific, 144 (13%) North American, and 119 (11%) other populations.

Secondary end points assessed overall survival, time to prostate specific antigen (PSA) progression, PSA response rate, and objective response rate.

Around 47% of patients had experienced PTEN loss by immunohistochemistry. Among this population, the PSA response rate was 11.8% (95% CI, 4.3-19.3) greater in the experimental arm (83%) than in the control arm (72%).The difference was less significant in the intention-to-treat population, where the PSA response rate between the ipatasertib and placebo group was 5.9%.

In addition, the median time to PSA progression was greater with ipatasertib in both the PTEN-loss-by-immunohistochemistry and intention-to-treat population.

Overall, AEs were observed in 70% of patients treated with the ipatasertib-abiraterone combination.Treatment was discontinued in 5% of the placebo group and 21% of the ipatasertib group in response to AEs. Two patients died in relation to the AEs from both the placebo and ipatasertib group.

One limitation that the authors noted was that most of the tumor samples were archival, and a percentage of patients might have developed PTEN loss during the time between sample collection and initiation of study treatment. Furthermore, next-generation sequencing could not determine the PTEN status of several tumor samples.The authors argued that the strong collaboration with independent assessments helped validate the investigator assessment of radiographical progression, which was therefore not a limitation.

The study authors concluded that “this study did not reveal a benefit with ipatasertib in the overall population but confirmed that combined AKT and androgen-receptor signaling pathways blockade with ipatasertib and abiraterone provided a significantly reduced risk of radiographical disease progression or death and improved clinical outcomes compared with androgen-receptor blockade alone with abiraterone in men with mCRPC with PTEN loss—a large subgroup of patients who have poor prognosis.”

The authors stated that future studies should evaluate the effect of early and optimal prophylactic measures to prevent the need for drug discontinuation.

Sweeny C, Bracarda S, Sternberg CN, et al.Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150):
a multicentre, randomised, double-blind, phase 3 trial. 

https://doi.org/10.1016/S0140-6736(21)00580-8

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Patients with metastatic castrate-resistant prostate cancer and PTEN-loss tumors experienced improved radiographical progression-free survival with ipatasertib plus abiraterone. 

Ipatasertib Plus Abiraterone Improves Progression-Free Survival in Prostate Cancer Subtype

Making lunch for a patient might not be the first task one envisions when thinking about oncology nursing. Luckily, that didn’t stop one nurse from helping a patient who was unable to prepare lunch for herself during chemotherapy.

That nurse is Kathleen Lutz, RN, NP-BC WH, and she addresses a variety of tasks every day to make the journey for her patients a little more comfortable. After 23 years at NYU Langone Health in New York, New York, as a nurse practitioner (NP), Lutz has seen cancer care develop dramatically during her career.

“I started practicing nursing in 1988 after graduating from Molloy College in Rockville Centre, New York. In 1997, I earned my post master’s nurse practitioner (degree) in women’s health from Stony Brook University. By 1998, I was the third NP credentialed to practice as a nurse practitioner at NYU Medical Center and the first NP in ob/gyn at the center, so I basically paved the way for the future of APN within the department of ob/gyn,” she said in an interview with 

Lutz knows that oncology nursing is her calling. Despite some hesitancy moving to her current practice, on her first day working in outpatient gynecologic oncology she fell in love with the facet of nursing. She loved the level of care, the level of involvement with the patients, and the amount of relationship building that comes from helping a patient across the entire spectrum of cancer.

Oncology nurses help their patients through an avalanche of challenges. It is difficult for Lutzwhen she sees patients without a support system at home. “One of the big challenges is when we have a patient with no social support,” she said. “It means getting creative and finding the resources to get them back and forth to appointments and getting them medications.” She explained that patients without support systems need daily phone calls and more frequent home care visits to ensure that somebody is checkingin on a regular basis.

Lutz believes in an interdisciplinary team. She consistently reaches out in the community to see what resources can be provided for patients. This includes getting social services and nutritionists involved, as well as informing the regular staff nurses to ensure they know which patients need this extra level of support.

“I bring [the patients without support] in a little bit more often since they don’t have anybody, and I help coordinate their rides and such,” Lutz said, adding that she also arranges services such as Meals on Wheels for these patients and allows them to call her on the weekends.

Her enthusiasm for the patient’s well-being is clear to all who know her. Bhavana Pothuri, MD, who works at NYU Langone with Lutz, said, “Kathleen is extraordinary in her commitment to the care of the gynecologic oncology patient and is most deserving of this [recognition]. I have worked with her for 15 years and can say she is undoubtedly the most dedicated nurse I have ever worked with.”

This is not the first time Lutz has been spotlighted for being an excellent oncology nurse. At the end of 2014, Lutz received the Advanced Practice Nursing Excellence Award from NYU. Her colleague, Erin Reese, RN, NP-BC WH, nominated her, citing an example of a patient for whom Lutz made lunch every time she came in for chemotherapy. This award served as a pivotal moment for Lutz, causing her to consider the positive impact of her actions. She explained, “Getting that award helped me realize that I am making a difference. I am making things better for patients and I am doing the right thing….I am on the right path.”

Her role as an advanced practice nurse also lends itself to an emphasis on excellent supportive care. Lutz cares for complex gynecologic patients during diagnoses, surgery, and chemotherapy treatments. Along the way, she supports them by providing an environment where they can go through the journey successfully. She also deals with end-of-life issues when appropriate, working closely with the supportive oncology team to help transition patients who go from active treatment for cancer to best supportive care. This entails working closely with the patients and their families.

Lutz said she is always inspired by the evolution of new drugs and successful treatments. A special moment in her career was recognizing that today she can say that patients are living longer, better, quality lives with cancer. She enjoys knowing she can make a difference in women’s lives and looks forward to what the future brings in cancer care, including the different trials and drugs that will arrive.

During the COVID-19 pandemic, Lutz helped orchestrate infusion appointments locally when going to New York City was not feasible for patients. This involved spending many hours on the phone with patients to arrange for them to receive their chemotherapy in 1 of the 2 satellite centers on Long Island. Step 1 involved a telehealth visit where her team would make all the necessary assessments. On the day of the treatment, she would check in with the laboratories, look at the numbers, and ensure all the orders were set and signed so the patient would have a seamless appointment experience.

For approximately 9 months, the team worked tirelessly to help patients navigate the system so they could receive their treatment without traveling to 1 of the major epicenters of the pandemic. Lutz reminisced that “it was a challenge, and an exciting one, and I hope never to go through it again.”

When Lutz thinks about excellence in oncology care, she finds herself repeating the importance of having “big shoulders.”

“You need a lot of wiggle room,” she said. “It is important to recognize that patients are facing the most stressful event of their lives. One needs to allow [patients] multiple chances. Sometimes a patient might get angry, and that’s okay. You can’t get mad at your patients.”

Her message to other oncology nurses is to take a step back, put yourself in the patient’s position, allow them room to express themselves, and support them along the way.

Lutz understands that oncology nurses have to be 100% vested in what they do to be successful. She knows it is that level of commitment that makes her team what she calls “a successful family” and is happy to say she loves being an oncology advanced practice nurse.

From orchestrating local infusion appointments to making lunch for a patient, Kathleen Lutz, RN, NP-BC WH, constantly strives to provide an excellent level of supportive care.

Oncology Nurse Champion: Kathleen Lutz

In this episode of “The Vitals,” we spoke with Kate Esselen, MD, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, about patients with gynecologic cancer who don’t comply with prescribed treatment in response to financial distress or toxicity.

Dr. Esselen is the corresponding author on the study, titled “Evaluating Meaningful Levels of Financial Toxicity in Gynecologic Cancers,” which was published in the International Journal of Gynecologic Cancer. The data found that nearly half of patients with gynecologic cancer experienced some degree of financial distress and that patients with severe financial toxicity were significantly more likely to engage in behavioral cost-coping by medication non-compliance (adjusted risk ratio, 4.6; 95% CI, 1.2-18.1).


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“[Drug adherence] seems like a problem we could potentially solve or, at least, make much better, and we are not really doing enough right now to do that.”


Addressing Medication Non-Compliance and Financial Toxicity in Patients with Gynecologic Cancer

Single infusions of ciltacabtagene autoleucel (cilta-cel)were associated with early, deep, and durable responses in patients with relapsed or refractory multiple myeloma who were heavily pretreated, according to study results published in 

The single arm, open label, phase 1b CARTITUDE-1 study, evaluated 97 patients who were treated with single cilta-cel infusions at the recommended phase 2 dose (0

75 x 106 CAR-positive viable T cells per kg). There were 113 participants, of which 97 received cilta-cel infusion treatments.

The overall response rate was 97% (95% CI, 91.2–99.4), including 65 patients (67%) who achieved stringent complete response. The 12-month progression-free survival (PFS) rate was 77% (95% CI, 66.0–84.3) and overall survival (OS) rate was 89% (95% CI, 80.2–93.5). Median PFS and OS had not yet been reached as of the September 1, 2020, clinical cutoff. While the time to first response was 1 month, responses reportedly deepened over time.

“The rapidity and depth of response further suggest the potential of CAR T-cell therapies for changing the multiple myeloma disease course,” said lead authors, Jesus G Berdeja, MD, Sarah Cannon Research Insitute, and Deepu Madduri

MD, Mount Sinai Medical Center. They expressed that “Cilta-cel is a structurally differentiated CAR T-cell therapy featuring two BCMA-targeting single-domain antibodies designed to confer avidity. Cilta-cel showed unprecedented clinical activity compared with other novel anti-myeloma treatments in comparable study populations.”

The trial included patients with multiple myeloma who were 18 years and older. All participants had received 3 or more lines of therapy or were double refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, prior to the initiation of the trial.

Single cilta-cel infusions began 5 to 7 days after the start of lymphodepletion and were administered at the target dose 0.75 × 106 CAR-positive viable T cells per kg.

The authors noted that the previous frequent use of lenalidomide and autologous stem-cell transplantation (ASCT) may have resulted in myelodysplastic syndrome or acute myelogenous leukemia in the study.In addition, a total of 6 adverse event (AE)-related deaths occurred during the study. The authors argued that both the incidence of myelodysplastic syndrome or acute myelogenous leukemia, as well as the number of fatal events, were comparable to total incidences reported in other populations of heavily pretreated patients with multiple myeloma.

The findings also showed that cytokine release syndrome occurred in 92 patients. Most cases were grades 1 or 2 and almost all cases were resolved through treatment with tocilizumab, corticosteroids, and anakinra. In comparison to another anti-BCMA Car T-cell therapy, the median time to onset of cytokine release syndrome was much longer (2 vs 7 days, respectively). The study authors explained that the low-weight-based dose of infused CAR T cells might be responsible for the cilta-cel safety profile.

Twenty-one percent of patients experienced neurotoxicity; out of which immune effector cell-associated neurotoxicity syndrome (ICANS) accounted for 17%. While the incidence, type, and grade differ from other investigational CAR T-cell therapies, the number of AEs was comparable to those reported with those therapies.

Further studies (CARTITUDE-2 and CATITUDE-4) assessing cilta-cel will address outpatient dosing in order to reduce AEs.

“To minimize risk for patients in the ongoing cilta-cel clinical development program, monitoring and mitigation strategies were implemented, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of cytokine release syndrome and ICANS, handwriting assessments for early detection of neurotoxicity symptoms, and extended monitoring and reporting time for neurotoxicity up to 1 year after cilta-cel infusion,” the authors concluded. “Overall, cilta-cel has a manageable safety profile at the recommended phase 2 dose that is generally consistent with the current understanding of CAR T-cell therapy.”

Berdeja JG, Madduri D, Usmani SZ, et, al. Ciltacabtagene autoleucel, a B-cell maturation antigen- directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. 

https://doi.org/10.1016/S0140-6736(21)00933-8

At 12 months, 97% patients treated with single infusions of cilta-cel had responded to the therapy. 

Cilta-Cel Induces Deep and Durable Responses in Patients with Multiple Myeloma

The FDA approved pembrolizumab (Keytruda) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, to be continued as an adjuvant monotherapy after surgery.

The approval was based off findings from the randomized, multicenter, double-blind, placebo-controlled KEYNOTE-522 trial (NCT03036488). Data from this study indicated that the use of pembrolizumab as a neoadjuvant therapy with chemotherapy significantly increased the pathologic clinical response. The findings showed a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; 

In addition, adjuvant pembrolizumab following surgery displayed a favorable trend in event-free survival (EFS): 16% vs 24%, respectively (HR, 0.63; 95% CI, 0.48-0.82).

The study reported that adverse events (AEs) were consistent with the preexisting safety profiles of each agent. The median duration of exposure to pembrolizumab was 13.3 months. Fatal reactions from pembrolizumab treatment occurred in 0.9 % of patients. Serious AEs occurred in a little less than half (44%) of patients and included febrile neutropenia, pyrexia, anemia, and neutropenia. The most common AEs resulting in the permanent discontinuation of pembrolizumab were increased alanine aminotransferase, increased aspartate aminotransferase, and rash.

“Even when TNBC is diagnosed early, 30% to 40% of patients will suffer cancer recurrence after standard neoadjuvant chemotherapy and surgery,” said Joyce O’Shaughnessy, MD, chair of Breast Cancer Research, Baylor University Medical Center, Texas Oncology, U.S. Oncology, Dallas, Texas, in a press release. “Therefore, there is a high unmet need for new treatment options. Today’s approval is very welcome news and has the potential to change the treatment paradigm by now including an immunotherapy as part of the regimen for patients with high-risk early-stage TNBC.”

The study evaluated patients who were previously untreated, non-metastatic, and had been diagnosed with centrally confirmed TNBC. Participants were randomized 2:1 to receive either 200 mg of pembrolizumab or preoperative placebo paired with 4 cycles of carboplatin and paclitaxel, continued with 4 cycles of doxorubicin or epirubicin and cyclophosphamide. Following surgery, the 2 groups were then treated with either pembrolizumab or placebo as a monotherapy for either 9 cycles or until unacceptable toxicity was reached. Patients were separated by nodal status, tumor size, and carboplatin schedule.

End points included pathologic complete response and EFS. pCR was defined as an absence of invasive cancer in the breast and lymphs (ypT0/Tis or ypNO) while EFS was measured from the time of randomization to the first occurrence of disease progression. Secondary end points included partial complete response where pCR was defined as ypT0 ypN0 and ypT0/Tis, overall survival and efficacy in the pD-L1 L1þ population.

The age of participants ranged from 22 to 80 years and the mean age was 49. Ninety-nine percent of the participants were female, and 64% were white.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” expressed Vicki Goodman, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with KEYTRUDA is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

This KEYTRUDA combination is the first immunotherapy regimen approved for high-risk early-stage triple-negative breast cancer (TNBC). News release. MERCK. July 27, 2021. Accessed July 27, 2021. https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/


The FDA has approved the first immunotherapy, pembrolizumab (Keytruda), to treat patients with high-risk early-stage triple-negative breast cancer.


FDA Approves Pembrolizumab for High-Risk Early-Stage TNBC

An updated consensus on liquid biopsy to detect non-small cell lung cancer (NSCLC) use has been published by the International Association for the Study of Lung Cancer (IASLC).

The statement argues that liquid biopsy is now a favored method of molecular testing in various clinical settings and that it has demonstrated that it is effective in conjunction with tumor tissue testing.

 In addition, liquid biopsy offers unique opportunities such as serial monitoring and detection of minimal residual disease, according to the statement. Going forward, the IASLC expects a significant increase in the use of liquid biopsy.

The report discusses the inherent limitations of tumor tissue testing, which has traditionally been considered the gold standard for molecular analyses and argues that liquid biopsy approaches allow more varied methods of circulating analytes. According to the report, plasma circulating tumor DNA (ctDNA) represents the most widely studied and generally accepted alternative to tumor genotyping in solid tumors, including NSCLC.

“It is notable that the IASLC has taken the lead in detailing the current state of the art in this rapidly expanding field,” stated Gandara, MD, director of thoracic oncology, professor of medicine emeritus, in a news release. “Non-small cell lung cancer, in particular, is an ideal disease area for application of liquid biopsy due to the increasing availability of targeted therapies for this genomically complex malignancy. Liquid biopsy, and especially plasma ctDNA, can be used in many clinical settings where tissue is not applicable, such as the detection of minimal residual disease (MRD).”

The report builds upon a statement released by the IASLC in 2018 and was coauthored by a group of distinguished international lung cancer clinicians and experts.

In the report, the recommendations are as follows:

In clinical practice, ctDNA collection, sample handling and automated processing should be performed using standardized and clinically validated procedures to reduce operator variability and false-negative results.

Due to the growing number of guideline-recommended oncogene targets to be assessed in advanced NSCLC, testing of plasma ctDNA should be performed by a clinically-validated next-generation sequencing (NGS) platform rather than single gene PCR-based approaches, both in treatment-naïve patients and those associated with multiple mechanisms of acquired resistance to targeted agents. Where plasma NGS is not available due to technical and/or economic constraints, single gene or low multiplex-based approaches may represent appropriate alternatives. Use of limited PCR analysis for 

mutations as the initial step in molecular assessment, for example, remains highly relevant in areas of the world where the 

mutation rate is high. However, single gene testing should not be considered complete, and if negative, serial testing for additional actionable biomarkers must be pursued.

The benefit of tissue and plasma NGS is now established in several clinical practice settings. It is anticipated, due to broad-based coverage of requisite oncogenes, decreased turn-around times and emerging data on cost effectiveness, that in the near future NGS will become increasingly available worldwide. Implementation of a multidisciplinary MTB to assist clinicians in treatment decision-making is advisable, as described above.

Plasma ctDNA can now be considered a valid tool for genotyping of newly diagnosed patients with advanced NSCLC, and results are often complementary to tissue analysis. At the time of acquired resistance after tyrosine kinase inhibitor (TKI) therapy in an oncogene-driven NSCLC, initial use of ctDNA is preferred for determination of mechanisms of resistance ("plasma-first”), with repeat tissue biopsy if plasma ctDNA is uninformative. Due to ease of serial sampling and high patient acceptance, ctDNA is also emerging as the preferred method for real time monitoring.

In patients with oncogene-addicted NSCLC, liquid biopsy is emerging as not only complementary to tissue-based analysis but also acceptable as the initial approach (“plasma first”) for biomarker evaluation at the time of diagnosis, as well as for monitoring the efficacy of targeted therapies. Finally, a plasma-first approach is appropriate for identification of mechanisms of acquired resistance to targeted therapies in many clinical settings.

Indications for liquid biopsy in patients with non-oncogene addicted NSCLC are less well-defined at this time, although there are several promising areas of investigation. As noted above, tumor mutation burden is an emerging biomarker, pending completion of ongoing prospective randomized trials and refinement of methodology.

The 2021 World Conference on Lung Cancer, which will be held this upcoming September, will present a series of abstracts related to liquid biopsy methodologies and offer information regarding lung cancer screening, diagnoses, and therapeutic efficacy.

IASLC issues consensus updated report on liquid biopsies. IASLC. Press release. July 8, 2021.

Rolfo C, Mack P, Scagliotti GV, Aggarwal C, Arcila ME, Barlesi F, Bivona T, Diehn M, Dive C, Dziadziuszko R, Leighl N, Malapelle U, Mok T, Peled N, Raez LE, Sequist L, Sholl
L, Swanton C, Abbosh C, Tan D, Wakelee H, Wistuba I, Bunn R, Freeman-Daily J, Wynes M, Belani
C, Mitsudomi T, Gandara D, Liquid Biopsy for Advanced Non-Small Cell Lung Cancer: A Consensus Statement from The International Association for the Study of Lung Cancer (IASLC), Journal of Thoracic Oncology (2021), doi: https://doi.org/10.1016/j.jtho.2021.06.017.

The International Association for the Study of Lung Cancer (IASLC) has published an updated consensus on the use of liquid biopsy in screening non-small cell lung cancer (NSCLC).

Updated IASLC Report Calls Liquid Biopsy Preferred Method of Molecular Testing

The FDA has granted a breakthrough therapy designation (BTD) for venetoclax (Venclexta) in combination with azacytidine (Vidaza) for adult patients with previously untreated intermediate-, high-, and very high-risk myelodysplastic syndrome (MDS).

The BTD is based on the interim results from the ongoing phase Ib M15-531 (

) study, in which the combination of venetoclax plus azacytidine has generated preliminary evidence that the therapy results in superior improvement over existing therapies.

“Higher-risk MDS is associated with poor prognosis, reduced quality of life, and limited treatment options,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, in a news release. Garraway expressed hope that the agent’s approval represents potentially improved treatment outcomes for this patient population.

The trial’s main objective is to ascertain the recommended phase 2 dose and dosing schedule of the venetoclax/azacytidine combination, as well as to assess the safety profile and pharmacokinetics of the therapy.

Venetoclax functions by selectively binding and inhibiting the B-cell lymphoma 2 (BCL-2) protein. It is a targeted medicine designed to eliminate cancer cells by limiting apoptosis, or the process in which BCL-2 accumulates and stops cancer cells from self-destructing.

This is the sixth breakthrough therapy designation that venetoclax has received for treatment of hematological cancers. It has also received BTDs for untreated chronic lymphocytic leukemia (CLL), 2 for relapsed or refractory CLL, 2 for previously untreated acute myeloid leukemia (AML), and 1 for MDS.

Roche stated in a new release that, “every year in the US, approximately 10,000 people are diagnosed with MDS and the median survival for those with higher-risk MDS is approximately 18 months.” It is hoped that the Ib M15-531 interim results and consequent BTD indicate that improved treatments for patients with higher-risk MDS are in development.

FDA grants breakthrough therapy designation for venclexta in combination with azacitidine for the treatment of patients with myelodysplastic syndromes. Roche. News release. July 21, 2021. Accessed July 21, 2021. https://www.roche.com/media/releases/med-cor-2021-07-21.htm

The FDA has granted a breakthrough therapy designation for venetoclax following interim results from the ongoing M15-531 trial. 

Venetoclax Receives Breakthrough Therapy Designation for Treatment of Myelodysplastic Syndrome (MDS)

An Unplanned Journey That Led to a Lifelong Career as an Oncology Nurse

Lisa Cusaac, MSN, RN, OCN, began her nursing career running away from oncology. In fact, that specialty was the last thing on her mind.

“I never wanted to be an oncology nurse,” Cusaac shared. “My grandma always told me you should help out oncology patients, but I think I ran the furthest away from it.”

Cusaac had prior experience caring for someone with cancer, and she wasn’t ready to commit her life to working in that field. When Cusaac was about to start college, her grandmother was diagnosed with pancreatic cancer. Her grandmother needed help changing her dressings following a painful procedure to treat the cancer. Cusaac, who was on college break, would go to help her, but she recalls how difficult it was to see her grandmother in so much pain and agony.

“I respected the oncology nurses,” she said. “I got to know some of them, and I respected them, but I never thought I wanted to have anything to do with cancer. That was my first introduction and I saw it as painful and certainly not comforting.”

However, something rather unexpected happened when she signed up for the Nurse Tech Program at Georgetown. She was placed in the endoscopy department, where she cleaned the scopes used for colonoscopies and upper endoscopies. She would also interact with patients, some of which were receiving a diagnosis of cancer.

Across the hall from the endoscopy department was the bone marrow transplant unit, and there was a need for a nurse tech. Cusaac volunteered, and that’s where everything changed. She fell in love with the practice. She recognized that the patients needed so much care, and she was inspired by the cutting-edge science with which she would be working alongside. Surrounded by diverse patients who all needed a high level of support, she reminisces on how she knew she was in a position where she could make a difference. And so, she began her career there as a recent graduate.

Cusaac has now been at MedStar Georgetown for 25 years, working in many different facets of oncology. She has cared for bone marrow recipients, patients with hematologic malignancies, and patients with breast and other solid organ cancers. Some of Cusaac’s previous roles included serving as the Inpatient Assistant Manager of the Bone Marrow Transplant and Hematology Unit, as well as the Manager of the Outpatient Chemotherapy Infusion Center and Clinical Trial Infusions Centers. She currently oversees the nursing delivery of care and the supportive delivery care in the Lombardi Comprehensive Cancer Center.

Addressing Biases and Being a COVID-19 Vaccine Ambassador

Last spring, Cusaac spent time addressing racial biases in the workplace following the murder of George Floyd. The incident made her reflect on her own biases. She participated in the Equity, Diversity and Inclusion (EDI) taskforce. The work of this group sparked conversations within the hospital. The task force shared books and links to useful articles, addressed topics such as microaggressions and, most importantly, provided everyone with a safe place to speak.

She also became a COVID-19 vaccine ambassador at MedStar Georgetown. As she tells it, the hospital was about 75% vaccinated (vaccinations although not required, were strongly encouraged). Part of her job included talking to staff members who had not yet been vaccinated, many of which were minority members, and taking the time to dispel some myths surrounding the vaccine as well as to emphasize the importance of getting vaccinated.

John Marshall, MD, who works with Cusaac at Medstar Georgetown stated that, “Without Lisa, we would not have managed the pandemic. Without Lisa, we would not be managing the nationwide oncology nursing shortage. Lisa leads by example. She knows how to do, and often finds herself doing, most all the jobs we ask of nursing.”

Cusaac epitomizes a health care champion. She notes how she strives daily to embody the MedStar Georgetown University Hospital’s mantra of 

, or care of the whole person. Sometimes this means taking care of a patient’s family and providing supportive care throughout the cancer journey. Other times, it includes taking a moment to ask the patient about how they’re doing and what they truly want.

Cusaac remembers a powerful moment that forced her to stop and think. A child who received a bone marrow transplant and experienced countless hospitalizations, remissions, failed treatments, and therapies, said to her that “death is not defeat for me.” The boy then went on to say that he would never have another CT scan, never have another injection, and never have to be hospitalized and separated from his family. That has stuck with Cusaac forever. That conversation helped her realize that a patient’s quality of life is more important than the quantity of days. Oncology nurses always want to extend the days, months, and years of their patients, but, in her words, “if our patients are miserable, then what are we doing?”

She makes it her personal priority to always advocate for the patient. And, according to Marshall, she always does it with a kind smile on her face.

As for what she would say to fellow oncology nurses, it is this: “As a nurse we have to be present, and we have to be flexible. Each patient has their own journey, and each patient responds and reacts differently. No two patients are alike. I have to be patient, I have to be flexible to their individualized treatment plan, and being present in the moment is most imperative. I can’t be so task oriented, I have to remember that there is a person in front of me. They are not a name and a date of birth, not a number or medical record. They are a human being.”

Lisa Cusaac never planned on being an oncology nurse. However, 25 years later she has spent her entire career providing care for patients with cancer and being an Oncology Nurse Champion. 

Oncology Nurse Champion: Lisa Cusaac

The investigational drug ficlatuzumab combined with chemotherapy showed signs of clinical efficacy in the treatment of patients with relapsed/refractory acute myeloid leukemia, according to data from an early-phase trial published in 

The study authors observed a complete response to treatment in 9 of the 17 patients enrolled on the trial. Four of the patients who achieved a complete response showed no signs of minimal residual disease. The reported progression-free survival (PFS) among those who achieved a response was 31.2 months. An overall survival has not yet been reached.

Of note, 10 patients (8 of which achieved a response to the combination) received an allogeneic hematopoietic cell transplant. Six of those patients, according to a press release on the results, remain in remission as of the last follow-up.

“By comparing pre-treatment to post-treatment blood samples using state-of-the art single-cell mass cytometry and RNA sequencing, we observed that ficlatuzumab successfully suppressed (hepatocyte growth factor) signaling, and we also identified biomarkers of treatment response and resistance,” said the study’s lead author Victoria Wang, MD, PhD, an assistant professor of hematology and oncology at University of California, San Francisco, in the release. “This approach provided novel insight into the molecular changes that occur upon treatment, which could have clinical implications for tracking treatment response or identifying patients likely to respond.”

Peripheral blood mononuclear cells were collected at baseline and again at different timepoints after the initiation of treatment. These collections were analyzed for molecular changes as responses to treatment.

The data demonstrated that treatment with ficlatuzumab was associated with attenuated phosphorylation of MET, the receptor for the hepatocyte growth factor (HGF). This confirmed the on-target inhibition of HGF. Patients whose disease responded to treatment experienced reduced phosphorylation of the S6 protein and increased expression of genes involved in myeloid and leukocyte activation. Patients whose disease did not respond to treatment experienced increased HGF expression, increased phosphorylation of S6, as well as further expression of the genes involved in protein translation, cell adhesion and type I interferon signaling.

The most common adverse event (AE) that the study authors observed in the patient population was febrile neutropenia. There were two instances of a serious AE, and one death. However, that death was deemed to be unrelated to the use of ficlatuzumab.

The aim of the study was to assess the safety and efficacy of the investigational drug’s ability to target a shared chemical pathway in combination with single-agent chemotherapy in patients with relapsed/refractory AML. Ficlatuzumab, the investigational drug, is a monoclonal antibody that functions by binding HGF to prevent it from activating MET signaling and allowing tumor growth. Ficlatuzumab, according to the release, targets extracellular factors as opposed to cancer-specific mutations. This is important because many patients in this population have higher levels of circulating HGF.

The study authors noted that although the early findings show promise in this patient population, further research is needed to validate the findings from this phase 1 portion of the trial.

“The 53% response rate was quite striking to us since historical response rates for the standard-of-care treatment are in the 30% range,” senior study author Charalambos Andreadis, MD, a professor of clinical medicine at UCSF, said in the release. “While these results need to be validated in a larger study, they suggest that ficlatuzumab in combination with single-agent chemotherapy may lead to better responses with less toxicity in patients with relapsed/refractory (acute myeloid leukemia).”

EurekAlert News Release. Ficlatuzumab plus chemotherapy shows promise for the treatment of patients with relapsed/refractory acute myeloid leukemia. Published July 16, 2021. Accessed July 16, 2021. https://www.eurekalert.org/pub_releases/2021-07/aafc-fpc071421.php

The combination of ficlatuzumab and chemotherapy demonstrated some promising results in a small group of patients with relapsed/refractory acute myeloid leukemia. 

 Early Evidence Shows Investigational Therapy-Chemo Combo May Be Effective in Acute Myeloid Leukemia

Following a blinded reassessment by the Independent Review Committee (IRC), the FDA has requested that oncopeptides AB agree to a partial pause in clinical studies involving melflufen (melphalan flufenamide). Oncopeptides will collaborate with the FDA to continue to uncover the benefits and risks associated with the agent and its impact in the treatment of relapsed refractory multiple myeloma.

Melflufen demonstrated superior progression free survival (PFS) compared to pomalidomide with a hazard ratio (HR) of 0.792 in the recent phase 3 OCEAN Study. However, upon reviewing the overall survival (OS) data, the FDA has requested the partial clinical hold.

OS, a secondary endpoint in the OCEAN study, induced an HR of 1.104 in favor of pomalidomide for the intention-to-treat population.

Melphalan targets the overexpressed aminopeptidases in multiple myeloma cells, which are associated with advanced disease and tumor mutational burden. By targeting aminopeptidases, the drug attempts to spare the healthy cells by initiating selective activity in the cancer cells.

Oncopeptides updated results and safety measures based on data from the head-to-head phase 3 Ocean study. The study measured the efficacy and safety of the combination of melfulufen plus dexamethasone against the combination of pomalidomide plus dexamethasone in patients with relapsed refractory multiple myeloma. There were 495 participants in total, from more than 100 hospitals across 21 different countries. Each patient had received 2 to 4 lines of therapy prior to the study.

The study began in 2017 and topline results were declared on May 25.

When preparing the clinical study report and regulatory documents, it became clear that the IRC was not provided with all necessary clinical database information at the time of their initial assessment, and, therefore, the data of 29 patients needed to be reassessed.

Oncopeptides has “performed analyses of the OS data and the company believes that the OS results are primarily explained by substantial HR differences between pre-specified subgroups in both directions,” the company stated in a news release.

Further investigation will determine whether melflufen will continue to be studied in clinical trials. In the meantime, oncopeptides plans to work with the FDA to expeditiously analyze the safety and efficacy of the drug.

Oncopeptides News Release. Updated results from phase 3 OCEAN study shows melflufen met primary endpoint of superior PFS – Overall Survival data lead to partial clinical hold. Published: July 8, 2021. Accessed July 8, 2021. https://www.oncopeptides.com/en/media/press-releases/updated-results-from-phase-3-ocean-study-shows-melflufen-met-primary-endpoint-of-superior-pfs--overall-survival-data-lead-to-partial-clinical-hold.

A trial evaluating melflufen in myeloma met its primary end point of progression free survival in the phase 3 OCEAN trial; however, overall survival was in favor of pomalidomide. 



Lindsay Fischer