Patient-reported outcomes, or PROs, include important measures for patients with cancer. However, with multiple validated tools to track them, clinicians may find themselves debating on which one to use.

Recent research analyzed survivor preferences in patient-reported outcome tracking, and in doing so, discovered important aspects of the cancer experience that they wanted to be communicated with their care team. In a recent interview with 

, study author Meagan Whisenant, PhD, assistant professor or research at the Cizik School of Nursing at UTHealth discussed the study – and the importance of patient-reported outcomes.

 Can you explain your study and why it was important to conduct?

 Recent evidence suggests that routinely and systematically monitoring cancer patient symptoms during treatment improves outcomes, including quality of life, functioning, ability to maintain therapy and even overall survival. However, there are a number of different validated questionnaires for asking patients about their symptoms and quality of life (QOL) and we are not sure whether patients have preferences about the types of questions they want to be asked and how they would like for their symptoms to be monitored. There are no existing best practices for routinely monitoring and managing symptoms in cancer outpatient care.

We asked 15 patients who were receiving treatment for cancer to complete 3 questionnaires that are frequently used in clinical care and research: the MD Anderson Symptom Inventory (MDASI), the Functional Assessment of Cancer Therapy-General (FACT-G), and the European Organization for the Research and Treatment of Cancer QOL Questionnaire-Core 30 (EORTC QLQ-C30)) and then conducted qualitative interviews to learn about their preferences for questionnaires.

What are the benefits in using patient-reported outcomes for patients with cancer?

Using validated patient-reported outcomes measures in cancer care provide the care team with reliable and valid information about how the patient is doing in terms of quality of life, symptoms, and functioning. This is especially important in outpatient care, when symptoms vary and change rapidly in the home setting. Unless the patient reaches out, the care team is often unaware of the status of the patient in between scheduled visits. Patients are often hesitant to reach out – in fact, in our work, we have seen that patients reach out to their care about 5% of the time when they are experiencing a moderate to severe symptom at home. Systematically monitoring symptoms facilitates communication between patients and providers in between visits and shifts the responsibility to initiate communication about symptoms away from the patient.

Using PRO measures routinely in cancer care has resulted in improved symptom-related communication, quality of life, symptoms, functioning, ability to tolerate and/or stay on prescribed treatment, reduced hospitalization and emergency room visits, and improved overall survival in research studies.

Participants described the importance of communicating various aspects of the disease and treatment experience to their care team, including their physical and emotional experience. They felt that validated questionnaires would help them communicate, especially if administered systematically. Participants felt that some of the questions on these PRO questionnaires were similar to the questions they were asked at clinic visits, especially the questions that ask about symptoms. Participants preferred shorter measures and preferred to have numbers and descriptors include in the response options. Importantly, participants were willing to complete PRO measures prior to every visit and the symptom burden measure (MDASI) specifically on a weekly basis in between visits.

What role do oncology nurses play in patient-reported outcomes?

Oncology nurses can recognize the importance of communicating with their patients about symptoms and QOL and facilitate systematic assessments using patient-reported outcomes measures. Because nurses are often the member of the interprofessional team that leads symptom management, they are key advocates in facilitating systematic symptom monitoring and management. Nurses can also be mindful of the need for brevity of questionnaires to reduce patient burden and select measures that are appropriate to the construct they wish to measure and the patient population in which the measure is being used.

What unanswered questions remain/what are next steps in this research?

We are currently conducting studies to better understand patient preferences for method of questionnaire administration (electronic versus paper and pencil; in the home versus in the clinic), preferred clinician response to various patient-provided symptom information (phone call, email, no response), and preferences for measure frequency and measure length in various cancer patient populations, from those in active treatment to those in survivorship. Additional next steps include conducting similar interviews with providers to better understand their preferences for facilitating systematic symptom monitoring and management, including their needs for resources such as decision support to assist in responding to PRO data.

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Patient-reported outcomes (PRO) hold valuable information on how patients are handling cancer treatment. Recent research analyzed which methods of PROs patients prefer. 

Study Examines Patient Preference in Patient-Reported Outcome Tracking

Data from the pivotal phase 3 KATHERINE (NCT01772472) has led to the addition of ado-trastuzumab emtansine (T-DM1; Kadcyla) to the HER2-positive breast cancer treatment arsenal, but the toxicities associated with the approach must be appropriately managed so that patients can continue to receive it, according to Jane L. Meisel, MD.

The phase 3 KATHERINE trial examined ado-trastuzumab emtansine (T-DM1; Kadcyla) vs trastuzumab (Herceptin) and showed that the former resulted in a 50% reduction in the risk of invasive disease recurrence or death (HR, 0.50; 95% CI, 0.39-0.64; 

 <.0001). These data led to the May 2019 FDA approval of T-DM1 for use as an adjuvant treatment in select patients with HER2-positive early breast cancer.

Notably, 25.7% of the patients in the T-DM1 arm experienced a grade 3 or higher adverse effect (AE) vs 15.4% in the trastuzumab arm. Additionally, 18% of patients in the T-DM1 arm experienced AEs that lead to discontinuation of treatment.1

“It's tricky because these patients have been through a lot,” Meisel said. “It's a diagnosis of breast cancer, first of all, and it is a relatively toxic, intense, up-front therapy. It’s not the easiest thing, but for many patients, particularly those with high-risk disease, it really does make a difference. We try to do all we can to support patients through that.”

® during an Institutional Perspectives in Cancer webinar on breast cancer, Meisel, an associate professor for the Departments of Hematology and Medical Oncology, and Gynecology & Obstetrics at Winship Cancer Institute, Emory University School of Medicine, discussed the use adjuvant T-DM1 and the management of associated toxicities and the benefit of the combination pertuzumab (Perjeta)/trastuzumab in HER2-positive breast cancer.

®: What were the implications of the phase 3 KATHERINE and FeDeriCa trials (NCT03493854) now that more mature data have read out?

: KATHERINE was a fascinating study because it not only allowed us to take a very high-risk group and randomize them to a potential intervention, but it also showed that they really did much better when, instead of being given just 1 year of trastuzumab after not achieving a pathologic complete response [pCR], they were switched over to adjuvant T-DM1. That 3-year progression free survival [PFS] difference of 11% is really statistically significant, as well as clinically significant, and this has changed the way we treat our patients. Routinely, we are switching [patients] over to T-DM1 as was done in KATHERINE, and I believe this will start to change outcomes, as we see more and more of these patients do better.

FeDeriCa was a study that looked at pertuzumab and trastuzumab given subcutaneously as opposed to intravenously, with the primary end point being pertuzumab concentration, so more of a pharmacologic/pharmacokinetic end point as opposed to a clinical end point. The authors also looked at PCR rates with the subcutaneous administration and found that both the trough concentrations as well as the PCR rates were the same with subcutaneous versus IV administration.

[This is an] intervention that changes convenience for the patient, and in terms of safety, particularly during the pandemic, [it can prevent] time spent in the infusion center. This is a preparation which, technically, could be given in one's home as opposed to even in the clinic. Certainly, for patients who want to have the port removed or don't want to receive IV treatment for longer than they have to, this offers an opportunity to do just a little injection as opposed to an infusion. In terms of quality of life for patients, which really is a huge [factor] after they've been through so much, this represents a major step forward.

Were there any prohibitive toxicities observed in KATHERINE?

In the study, approximately 18% of patients discontinued T-DM1 because of toxicity. Generally, the populations that we see in studies are inherently a motivated, relatively well population of patients, while those we see in clinic may have more comorbidities or may not be as motivated as those who choose to join trials. As such, more [efforts are needed] to monitor these patients and to encourage them to stay on the T-DM1 because it is a little more challenging than the pertuzumab/trastuzumab. However, the benefit is there, so when patients seem as though they're going to benefit and they fit the criteria for the trial, we do try to get them to stay on [the drug].

I find it works best if I tell patients about the possibility [of toxicity] in the beginning. When I describe the neoadjuvant, anti-HER2–directed regimen, I talk about the fact that we'll use their surgery as both a part of their treatment, but also as an information-gathering piece. The result of the surgery, whether they get to PCR or not, will inform the next step. If they get to PCR, [they] would [then receive] trastuzumab, likely plus pertuzumab, or switch to T-DM1 if they don't. Once I get closer to that time point after the surgery, and if the patient is going to receive T-DM1, then we talk about what that will look like.

Often, I do see the patients each visit with T-DM1, at least in the beginning, just to see whether they're experiencing [effects] like nosebleeds, gastrointestinal distress, or worsening neuropathy. These are some of the most common [effects] that we see with the T-DM1 regimens, so we prefer to get on top of these effects and manage them right away. [Then] patients can either make the decision to discontinue and go back to pertuzumab/trastuzumab if they need to or can feel empowered that we have ways to manage the AEs and get through as much of that year of T-DM1 as possible.

Could you elaborate on some of the strategies used to manage those toxicities?

With neuropathy, one of the main strategies that we have is gabapentin, which can be helpful. Additionally, there's solid clinical trial data that support that icing the fingers and toes during chemotherapy treatment helps prevent neuropathy from getting worse; that can also be empowering: to know that there's something they can do, or can try, to help with that. In terms of the nosebleeds, which can happen with T-DM1, it's important to keep the nostrils moist. Vaseline or nasal sprays [can be used] sparingly if the nosebleeds are particularly bothersome. If a patient is having recurrent nosebleeds, we will refer them to an ear, nose, and throat [specialist].

In terms of liver function abnormalities, we do encourage patients to not drink heavily while they're on treatment and to abstain from Tylenol or other medications that might interfere with liver function tests.

Also, [we see] fatigue, [which] is multifactorial. We certainly see that [when patients are] on breast cancer therapies of all kinds.

Turning to FeDeriCa, now that the subcutaneous administration is approved, do you believe that patients will be more likely to pursue that option if they experience a milder toxicity?

They might, because options are everything. Some patients may be sticklers for the data, who may say they want to wait a little longer and see more before they make the switch. For other patients, the pharmacokinetics, and the fact that it's FDA approved, may be enough for them. They may want to make the switch if they feel like it's palatable.

Insurance coverage may be another issue. I'm not sure that every insurance company is going to cover it to the same degree as they cover intravenous administration. Finances may play a role, but I do believe this is going to be something that has legs, for sure.

von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. 

. 2019;380(7):617-628. doi:10.1056/NEJMoa1814017

This article was originally published on OncLive as, "

Miesel on Managing Toxicities With T-DM1 in HER2+ Breast Cancer

Data from the pivotal phase 3 KATHERINE has led to the addition of ado-trastuzumab emtansine to the HER2-positive breast cancer treatment arsenal, but the toxicities associated with the approach must be appropriately managed so that patients can continue to receive it.

T-DM1 Toxicity Management in Breast Cancer

The American Society of Pharmacovigilance officially announced that today, March 24, is National Adverse Drug Event Awareness Day. In the oncology world, nurses are leaders in adverse event (AE) management.

While nurses are skilled in helping patients through a variety of symptoms – from nausea to neuropathy – communication barriers may exist between patients and providers, leading to unchecked toxicities that diminish patient health and quality-of-life. For example, research shows that patients receiving immunotherapy may not report AEs, in fear of being taken off treatment. In this situation, reassurance from the nurse is critical.1

Patients may also be unaware of what kind of AEs are important to look out for and report to their care team, or may not have a solid understanding of their cancer treatment plan.This points toward the importance of patient education.2

We want to hear from you on the biggest barriers to AE management in patients with cancer.

There is a lack of sufficient infrastructure (electronic medical records, etc) for the reporting and documentation of adverse events 

There is a lack of patient education on adverse events 

Clinicians do not have time to properly monitor and discuss adverse events with patients 

There are no barriers to adverse event management

Fecher LA, et. al. Ipilimumab and its toxicities: a multidisciplinary approach. 

https://doi.org/10.1634/theoncologist.2012-0483

Wood LS, Moldwer NP, Lewis C. Immune checkpoint inhibitor therapy: key principles when educating patients. 

: 10.1188/19.CJON.271-280. Accessed March 24, 2021.

We want to hear from you: what is the limiting factor in managing adverse events in patients with cancer? 

Adverse Event Management: What’s the Limiting Factor?

Intravenous (IV) cetirizine (Quzyttir) showed comparable efficacy to IV diphenhydramine for the prevention of infusion reactions (IRs) in patients with cancer who are undergoing treatment with an anti-CD20 antibody or paclitaxel, according to results from a prospective, phase 2 trial (NCT04189588) that were presented during the 

Findings showed that the IR rate in patients who received IV cetirizine was 11.8% (n = 2/17) compared with 17.6% (n = 3/17) in those who received IV diphenhydramine. One of 3 patients with breast cancer experienced an IR.

“This was the first prospective, randomized, controlled trial evaluating IV antihistamine pretreatment for the prevention of IRs,” Jarrod P. Holmes, MD, FACP, medical oncology at St. Joseph Health Medical Group, and coinvestigators noted in the poster presented at the meeting. “IV cetirizine was associated with less sedation, less time in the treatment center, and fewer treatment-related [adverse effects (AEs)] than IV diphenhydramine.”

Pretreatment with antihistamine for drug-induced hypersensitivity is recommended to be used with other chemotherapies, including paclitaxel, for patients with breast cancer. IV cetirizine is a second-generation IV antihistamine and has been shown to treat patients with acute urticaria with outcomes comparable to that of IV diphenhydramine but with fewer toxicities. The study authors suggested that IV cetirizine may also show promise as a pretreatment of IRs.

In the prospective, double-blind, randomized, controlled, phase 2 trial, investigators sought to compare the incidence of IRs to treatment with an anti-CD20 antibody, such as rituximab (Rituxan), or paclitaxel, following pretreatment with IV cetirizine (n = 17) or IV diphenhydramine (n = 17) during infusion.

IRs were defined as flushing, itching, alterations in heart rate and blood pressure, dyspnea, chest discomfort, acute back or abdominal pain, fever, shaking, chills, nausea, vomiting, diarrhea, skin rashes, throat tightening, hypoxia, seizures, syncope, or dizziness.

Pretreatment was given with a single IV dose of 10-mg cetirizine or IV diphenhydramine at 50 mg in 34 patients who were being treated with paclitaxel, rituximab or a rituximab biosimilar, or obinutuzumab (Gazyva) at the first cycle or retreatment after 6 months or in patients with persistent IRs while on maintenance or retreatment.

To be eligible for enrollment, patients had to be 18 years or older, could be male or female, and required treatment premedication with an antihistamine for hypersensitivity IRs linked with rituximab or paclitaxel. Those who had a high risk of developing tumor lysis syndrome, may have contraindications with an antihistamine, had received any antihistamine within 24 hours prior to receiving the study drug regardless of the administration route, and who had received an H2 antagonist in the prior 4 hours before receiving study drug, were excluded.

The primary end point of the trial was the incidence of IRs following pretreatment; the key secondary end point was sedation score due to IV antihistamines. Sedation was assessed by health care providers as well as patients on a scale of 0 to 4 (0 = none; 4 = extremely severe/asleep). Time to readiness for discharge served as another efficacy end point, the investigators noted in the poster.

The patient population comprised those with both hematologic and solid tumors, including breast cancer, and were enrolled between March 25, 2020 and November 23, 2020. An addition of patients receiving paclitaxel was added to the protocol in amendment 2 on August 10, 2020. Twenty-five patients had received an anti-CD20 agent and 9 had been given paclitaxel; those who had received the anti-CD20 drug had hematologic malignancies or immune disorders, while those who had paclitaxel had solid tumors, 3 of whom had breast cancer.

The median age of the participants was 66.0 years (range, 36-87), 35.3% were female, and most were White (76.5%) and not Hispanic or Latino (82.4%).

Additional data showed that the mean sedation scores in the IV cetirizine arm was 0.5 (0.72), 0.6 (0.61), and 0.1 (0.33) vs 1.3 (1.26), 0.9 (1.14), and 0.4 (0.71) in the IV diphenhydramine arm at 1 hour, 2 hours, and at discharge, respectively, as rated by the patients enrolled on the trial. Moreover, these data were similar with the health care provider­–rated sedation scores.

The median time for readiness for discharge was 24 minutes less with IV cetirizine compared with IV diphenhydramine, at 4 hours and 18 minutes and 4 hours and 42 minutes, respectively.

Regarding safety, fewer patients experienced treatment-related AEs with IV cetirizine (n = 2) vs IV diphenhydramine (n = 4). Treatment-emergent AEs (TEAEs) occurred in 8 and 9 patients, respectively. In the IV cetirizine arm, these TEAEs were mild in 2 patients, moderate in 4, severe in 1, and life-threatening in 1; none were fatal. In the IV diphenhydramine arm, 3 cases were mild, 5 were moderate, and 1 was fatal; no severe or life-threatening TEAEs were reported.

Overall, 2 and 4 TEAEs were possibly related to study treatment; there were 0 AEs that led to discontinuation of study treatment in either arm.

The TRAEs in the IV cetirizine arm included insomnia, dyspepsia, and malaise; in the IV diphenhydramine arm, these effects were diarrhea, injection site pain, headache, somnolence, dizziness, and lightheadedness.

In the poster, investigators noted that study limitations include the small sample size without formal statistics.

“However, the results of key secondary end points of sedation score, time to discharge, and safety profile are consistent with the results from the studies with IV cetirizine in acute urticaria,” the authors stated.

Holmes JP, Dasanu CA, Peguero J, et al. Aphase 2 exploratory study of intravenous cetirizine versus intravenous diphenhydramine in the prevention of hypersensitivity infusion reactions in patients with breast cancer and other malignancies. Presented at: 

 Miami Breast Cancer Conference; March 4-7, 2021; Virtual.

Intravenous Cetirizine Prevents Infusion Reactions From Paclitaxel in Breast Cancer, Other Tumors.

Intravenous cetirizine showed comparable efficacy to IV diphenhydramine for the prevention of infusion reactions in patients with cancer who are undergoing treatment with an anti-CD20 antibody or paclitaxel.

Preventing Paclitaxel-Related Infusion Reactions

Nurses should ask their patients with breast cancer about their history of depression, as it could be indicative of cancer-related fatigue they may experience, according to recent research published in 

The researchers analyzed levels of fatigue in 270 women with stage 0 to stage IIIA breast cancer. They collected data at the following points: at baseline; before (neo)adjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy; posttreatment; 6 months; 12 months; and 18 months. The goal of the study was to determine the individual factors that affected fatigue, as well as to see how fatigue changes over time.

“To our knowledge, few longitudinal studies to date have examined individual differences in the course of fatigue from diagnosis into survivorship to identify distinct profiles of fatigue over time, despite important implications for developing a more precise understanding of cancer-related fatigue and implementing personalized interventions,” the researchers wrote.

After collecting patient data, the researchers separated patients into 5 categories:

Increasing, where patients’ fatigue levels were initially low and then increased over time (9%)

Reactive, meaning that the fatigue increased at first and then decreased (8%)

Women who had preexisting or elevated depression, distress, and sleep disturbances were more likely to have higher levels of fatigue. Forty-four percent with high fatigue levels had a history of a depressive disorder before their cancer diagnosis, and nearly all of them (97%) had clinically significant sleep disturbances.

Those who had high levels of fatigue before adjuvant treatment were unlikely to see a spontaneous decrease in fatigue over the next year and a half, as shown by 78% of the women with high levels of fatigue at baseline. On the other hand, those with stable low levels of fatigue were comparable to noncancer controls.

“Thus, a previous psychiatric history, in combination with high levels of behavioral symptoms at the onset of treatment, may set the stage for persistent fatigue across the cancer trajectory and help to identify vulnerable women for early intervention,” the researchers wrote.

The researchers also observed an association – though it was not as strong – between disease and treatment and fatigue.

Women who were in the stable high fatigue group had a higher rate of mastectomy than any other fatigue levels – a finding that surprised the researchers. Additionally, they found that radiotherapy was associated with reactive fatigue.

“Advising patients about these different trajectories, and conducting regular assessments of fatigue at clinic visits, can help to identify vulnerable patients and intervene with those most in need, ultimately enhancing quality of life in the growing population of survivors of breast cancer,” the researchers wrote.

Bower JE, Ganz PA, Irwin MR, et al. Do All Patients With Cancer Experience Fatigue? A Longitudinal Study of Fatigue Trajectories in Women With Breast Cancer. 

Baseline fatigue levels, prior psychosocial history, and cancer treatment may all affect the fatigue trajectory in women with breast cancer. 

Depression History and Breast Cancer Treatments May Affect Fatigue Levels

While second-generation androgen receptors such as apalutamide (Erleada) and enzalutamide (Xtandi) have improved outcomes for men with nonmetastatic castrate-resistant prostate cancer (nmCRPC), they can come with adverse events (AEs) that are often unresolved, according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“The objective of the present study was to describe the patient characteristics, the frequency of a disease or adverse events amongst patients receiving apalutamide or enzalutamide [and] how these adverse events are managed in a real-world setting, and what is the health care resource utilization for these patients,” said study author Arif Hussain, MD, professor of medicine at the University of Maryland Medical System.

The researchers analyzed 368 patients with nmCRPC who were taking apalutamide and 333 on enzalutamide. In this group, 72% and 78.8% experienced 1 or more AE in the apalutamide and enzalutamide group, respectively. Hussain noted that they did not investigate outcomes for darolutamide (Nubeqa) because they did not have sufficient data on the drug at the time of the study.

The most common AEs in the apalutamide and enzalutamide groups were:

Fatigue/asthenia (30.2% vs 38.7%, respectively)

Notably, cognitive and mental changes were also observed in 5.4% of men on apalutamide and 7.8% of men on enzalutamide.

From the total group, the researchers further analyzed 125 patients on apalutamide and 125 patients on enzalutamide who experienced 1 or more AE for a more in-depth evaluation. Nearly three-fourths of this group was Caucasian; 84% and 88% had an ECOG score between 0-1; and the median prostate-specific antigen (PSA) score was 13 ng/ml and 11 ng/ml for apalutamide and enzalutamide, respectively.

Many patients on apalutamide and enzalutamide (43.6% vs. 39.4%, respectively) did not have their AEs resolved. For those who did have toxicities resolved, it took an average of 60 and 56 days for the apalutamide and enzalutamide groups, respectively.

The most common approaches for AE management in the apalutamide and enzalutamide arms were:

Treatment for the AE (36.8% vs. 39.2%, respectively)

The researchers ultimately concluded that there is a resource use burden to manage AEs for these agents, and patients and providers should discuss toxicities before deciding on a treatment regimen.

“The results demonstrate the importance of safety and tolerability, which should be key considerations and shared clinician-patient decision-making regarding androgen receptor inhibitor targeted therapy in nmCRPC patients,” Hussain said.

Jiang S, Varghese D, Appukkuttan S, et. al. Frequency, management, and resource use of adverse events (AEs) in nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients receiving apalutamide or enzalutamide: A real-world study. Presented at: 2021 Genitourinary Cancers Symposium. Feb. 11-13. Virtual. Abstract 217.

While the majority of patients on androgen receptor therapy experienced adverse events, more than a third did not have them resolved. 

Better Treatment Needed for Androgen Receptor Adverse Events

Fear of cancer recurrence is a common plight for people after they have completed cancer treatment, and recent research analyzed which patient characteristics were associated with higher rates of fear of recurrence.

 recently spoke with study author Jacqueline Galica, PhD, RN, about her findings – and what oncology nurses can do to help mitigate fear of recurrence in their patients.

 What puts oncology nurses specifically in a good role to discuss fear of recurrence with their patients?

: Nurses are often that first point of contact to the healthcare system, and we are in this really unique position of trust, and this unique relationship develops. So I envisioned that if we could clarify what are the characteristics of survivors who are most likely have highest fears of cancer recurrence, this could be used by oncology nurses who are regularly seeing these people coming back to the clinics in their follow ups. [Nurses can help by] having that recurring conversation and that assessment that goes on in those conversations. And so that's what I really was striving for – for this work to be useful for oncology nurses in in those settings.

What were your findings? Which patients and patient characteristics were at most risk to experience fear of recurrence?

We used a theory, Leventhal’s Common Sense model, which is a theory that's commonly used to understand fear of cancer recurrence. We used this to identify what could be important characteristics to look at amongst cancer survivors. We looked at a number of characteristics.

What we found was consistent with other findings: people who are younger, have higher fears of cancer recurrence. And this could be for a number of different reasons, families, etc. Those who identified as female had higher fears of cancer recurrence and those who identified as male. Interestingly, people who had been diagnosed longer – so they there was a longer duration since they were diagnosed – they had higher fears of cancer recurrence, versus people who are shorter in their in their duration. And that's really interesting, because longitudinal studies that follow people for years show there's no trend, there's no trends could be anything for fear of cancer recurrence over time, people who were continued to be followed up in this cancer survivorship clinic. So they’re coming back to the clinic years and years after they were diagnosed, had higher fears of cancer recurrence. And so we think it was those reminders of coming back to the clinic where there were their experiences, reminders of these cancer experience.

Interestingly, people's perceptions were a strong predictor of higher fear of cancer recurrence. For instance, it wasn't about people who had more symptoms, but it was people who had more symptoms that they believed or caused from their cancer or caused from their treatment, these people had higher fears of cancer recurrence. People with lower self-esteem had had higher fears of cancer recurrence. And interestingly, people who were more pessimistic, had actually a lower fear of cancer recurrence. This might be their type of coping strategy that they use; they're more likely to be more pessimistic or more likely to deny or disengage, give in to their circumstances.

What should nurses do if they identify patients who are experiencing or who are at high risk of experiencing fear of recurrence?

The first thing is to normalize that fear of cancer recurrence is a normal feeling after completing treatment for cancer. In our subsequent research, [we found that] people who've had their fear of cancer recurrence normalized [felt] liberated and that they weren't alone in this feeling. There wasn't something wrong with them with experiencing this feeling. So that is, first and foremost, to normalize. This is a normal reaction to completing cancer treatment.

But then, nurses have a very special role to provide education. This means educating: what are some symptoms to watch out for that could indicate a recurrence, when to report a symptom, who to report it to, what are some things that aren't symptoms of recurrence, but just maybe long-term symptoms or side effects from treatment. So just helping patients navigate those uncertainties can help reduce the likelihood of their fear of cancer recurrence.

Encourage patients to really engage in positive coping, stress reducing activities. So recreational hobbies, that they enjoyed pre-cancer, yoga meditation. Also, remind patients that there will be some triggers to further fear of cancer that will trigger fear of cancer recurrence, this may be the anniversary of their diagnosis, this may be a mammogram or some sort of follow up testing. It's normal to have these feelings coming back around those milestones. And so that that awareness about that, even asking things like, “it sounds like you've been worrying a lot about this. Can you tell me more about that?”.

Encourage that dialogue – it helps further to normalizing how patients are feeling or survivors are feeling. It's making it a part of their cancer care, and it's helping people externalize some of those feelings. Yeah, I think that's one of the things that nurses can do.

Fear of cancer recurrence is a common plight for people after they have completed cancer treatment, and recent research analyzed which patient characteristics were associated with higher rates of fear of recurrence. 

Patient Perceptions, Other Factors Linked to Fear of Recurrence

Patients with metastatic urothelial carcinoma (mUC) who had a higher tumor mutational burden (TMB) tended to have more immune-related adverse events (irAEs) than those with low TMB. Additionally, high TMB and irAEs rates were associated with better response rates with immunotherapy, according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“It has been shown previously in the literature that TMB serves as a candidate biomarker of clinical outcomes from immune checkpoint inhibitors in urothelial carcinoma. In addition, the immune-related adverse events have been associated with a better [immune checkpoint inhibition] efficacy in multiple cancers,” said study author Elie W. Akl, MD, of the Dana-Farber Cancer Institute.

“So, we hypothesized that the immune response against new antigens is partly responsible for [irAEs] and investigated the association between [irAEs] and TMB and response to [immune checkpoint inhibition].”

The study involved 101 patients with mUC who were being treated with immune checkpoint inhibition (either single-agent or combination) at the Dana-Farber Cancer Institute.

About a third of patients (32%) reported irAEs. Six patients had grade 1 irAEs, 20 patients had grade 2, and 6 patients had grade 3. Those who experienced irAEs had a higher average TMB (15.4/mb) than those without irAEs (9.8/mb). Notably, the cutoff for TMB-high was 10/mb (non-synonymous exonic mutations per megabase).

Ninety-four patients had radiological data available at the time of the study. Among them, 50% of patients with irAEs responded, to therapy, compared to only 16% of patients without irAEs (

“However, when both adverse events and response were included in the multivariable regression, the association between adverse events and TMB was not significant,” Akl explained.

Patients who experienced an irAE and had a high TMB had an overall response rate of 56%, about double the rate of patients who had an irAE but low TMB, at 28.6%. That finding was statistically significant. A total of 21.2% of patients with high TMB but no irAE responded, and 10.3% of patients with low TMB and no irAE responded.

The researchers did not find any correlation between TMB and grading of irAE.

Looking ahead, Akl said the further research is warranted to better understand the associations between TMB, irAEs, and immunotherapy response.

“Further evaluation in metastatic urothelial carcinoma is needed to confirm this relationship between TMB adverse events and response, a larger cohort and explore specific mutations signature that may be associated with immune-related adverse events,” he said.

Patients with metastatic urothelial carcinoma with higher tumor mutational burden and who experienced immune-related adverse events tended to have higher response rates to immune checkpoint inhibitor. 

High TMB, Adverse Events May Predict Immunotherapy Response in mUC 

Sapanisertib failed to show significant activity and a favorable toxicity profile in patients with refractory metastatic renal cell carcinoma (mRCC) regardless of mTOR or PTEN status, according to findings from a phase 2 study (NCT03097328) that were presented during the 2021 Genitourinary Cancers Symposium.

At a median follow-up of 10.4 months (range, 1.0-27.4), the objective response rate (ORR) was 5.3% (n = 2; 90% CI, 1.0%-15.6%). The median progression-free survival (PFS) was 2.5 months (95% CI, 1.8-3.7), and the median overall survival (OS) was 11.2 months (95% CI, 9.3-not reached).

“Sapanisertib had poor tolerability and minimal activity in patients with treatment refractory metastatic RCC, and there was no clear benefit among patients with mTOR or PTEN alterations,” Bradley McGregor, MD, lead study author, and clinical director of the Lank Center for Genitourinary Oncology, senior physician at Dana-Farber Cancer Institute, and instructor of medicine at Harvard Medical School, said in a virtual presentation of the data.

Treatment options following progression on a checkpoint inhibitor and VEGF TKI are limited for patients with mRCC. Approved rapalogs, which have modest activity in mRCC, inhibit only mTORC1, whereas sapanisertib inhibits the entire mTOR pathway by targeting mTORC1 and mTORC2.

The multicenter, single-arm study enrolled 38 patients with clear cell mRCC who had received at least 2 prior lines of therapy and non-clear cell mRCC who had received at least 1 prior line of therapy with an ECOG performance status of 0 to 2.

Patients underwent a mandatory baseline biopsy that evaluated PTEN status and over 477 genes, including TSC1, TSC2, mTOR, PIK3CA, and PTEN, prior to receiving 30 mg of oral sapanisertib weekly.

The primary end point was ORR. Secondary end points included PFS, OS, safety, and toxicity. ORR and PFS by PTEN immunohistochemistry status and oncopanel-identified mutations in the mTOR pathway served as correlative end points.

Regarding patient characteristics, the median age at the time of enrollment was 62 (range, 28-75). The majority of patients had clear cell histology (73.7%; n = 28), followed by non-clear cell RCC (26.3%; n = 10), which encompassed chromophobe RCC (n = 2), papillary RCC (n = 6), translocation RCC (n = 1), and unclassified RCC (n = 1). The majority of patients had intermediate-risk disease (76.3%; n = 29) per International Metastatic RCC Database Consortium risk assessment, followed by favorable- (13.2%; n = 5) and poor-risk disease (10.5%; n = 4).

The majority of patients were heavily pretreated, having received 4 or more prior lines of therapy (39.5%; n = 15). Though, patients who received 1 (13.2%; n = 5), 2 (21.1%; n = 8), and 3 (13.2%; n = 5) prior lines of therapy were also represented. A total of 5 patients (13.2%) had an unknown number of prior treatments.

The majority of patients had received a prior checkpoint inhibitor (75.8%; n = 25) but not an mTOR inhibitor (60.6%; n = 20).

Additional results showed that 2 patients experienced an unconfirmed partial response (PR; 5.3%), 15 patients experienced stable disease (SD; 39.4%), 17 patients experienced progressive disease (44.7%), and 2 patients were not evaluable (5.3%).

The median time on treatment was 1.6 months (range, 0.3-13.8). At the time of data cutoff, 2 patients remained on treatment (5.3%), 36 had discontinued treatment (94.7%), 29 had progressive disease (PD; 76.3%), 4 had unacceptable toxicity (10.5%), 1 withdrew (2.6%), 1 discontinued by patient decision (2.6%), and 1 discontinued by physician discretion (2.6%).

No clear benefit between mTOR and PTEN alterations and clinical benefit with sapanisertib was reported.

Among patients with intact PTEN (n = 12), 1 experienced a PR, 6 experienced SD, and 5 experienced PD. Among patients with diminished PTEN expression or PTEN loss (n = 7), 1 experienced an unconfirmed PR, 2 experienced SD, and 4 experienced PD.

Among patients with an mTOR pathway mutation (n = 6), 1 experienced an unconfirmed PR, 1 experienced SD, and 4 experienced PD. Among patients without an mTOR pathway mutation (n = 21), 2 experienced a PR, 1 experienced an unconfirmed PR, 8 experienced SD, and 9 experienced PD.

Treatment-related adverse effects consisted of nausea (50%; n = 19) fatigue (39%; n = 15, vomiting (34%; n = 13), mucositis (32%; n = 12), anorexia (21%; n = 8), diarrhea (18%; n = 7), rash (18%; n = 7), dyspnea (13%; n = 5), hyperglycemia (13%; n = 5), constipation (11%; n = 4), hyperkalemia (11%; n = 4), cough (8%; n = 3), dehydration (8%; n = 3), dry mouth (8%; n = 3), muscle weakness (8%; n = 3), pruritus (8%; n = 3), hyponatremia (5%; n = 2), elevated creatinine (3%; n = 1), myocardial infarction (3%; n = 1), syncope (3%; n = 1), and pneumonitis (3%; n = 1). No grade 4 or 5 toxicities occurred.

“Additional work is needed to find new targets for patients with advanced RCC,” concluded McGregor.


McGregor BA, Adib E, Xie W, et al. Biomarker-based phase II study of sapanisertib (TAK-228), an mTORC1/2 inhibitor in patients with refractory metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2021(suppl 6):306. doi:10.1200/JCO.2021.39.6_suppl.306

This article was originally published on OncLive as, "Sapanisertib Imparts Poor Activity and Toxicity Profile in Refractory mRCC."

Sapanisertib failed to show significant activity and a favorable toxicity profile in patients with refractory metastatic renal cell carcinoma (mRCC) regardless of mTOR or PTEN status. 

Sapanisertib: Poor Activity, More AEs in mRCC

The coronavirus disease 2019 (COVID-19) pandemic has increased symptom burden – including anxiety and depression rates – in patients with cancer, according to ongoing research presented at the National Institute of Nursing Research’s Symptom Science Advances in Oncology Nursing virtual event.

“Oncology patients, during COVID-19, are experiencing a very high symptom burden,” study author Christine Miaskowski, PhD, RN, FAAN, Sharon A. Lamb Endowed Chair in Physiological Nursing and professor in the department of physiological nursing at the UCSF Helen Diller Family Comprehensive Cancer Center, said during her presentation.

More than 600 cancer survivors completed an online survey about symptom burden, which were compared to statistics from patients before the COVID-19 pandemic and the general population. The majority were female; 40% were on active treatment; about 25% lived alone; and a third had metastatic disease.

“The general population is experiencing a high amount of stress during the COVID-19 pandemic,” Miaskowski said. “So in some ways, we’re adding insult to injury. There’s a large [body] of literature on the fact that a cancer diagnosis itself and treatment is stressful for patients. And now we add these stressors in the context of COVID-19.”

Before COVID-19, about 15% to 30% of cancer survivors reported high depression scores (indicated by a score of 16% or higher per the Center for Epidemiological Studies scale). This number increased to 40.7% during the pandemic, which was also higher than the general population, which had a 33.7% rate of depression.

Trait- and state-related anxiety rates also increased in cancer survivors during the COVID-19 pandemic, increasing from 30% and 50%, respectively, prior to the pandemic, increasing to 58.3% and 48.4% after. In the general population, there was a 31.9% rate of anxiety during the COVID-19 pandemic.

When it came to sleep disturbances, more than twice the amount of patients with cancer experienced the symptom (61.4%) compared to those without a cancer history (18%-30%) during the COVID-19 pandemic.

Additionally, many patients reported feelings of loneliness as a result of social isolation. Considering that the bulk of the participants in the study were White, educated, and finished with active treatment, Miaskowski noted her concerns for those in more vulnerable populations and what they may be going through.

“I have a long list of questions about what’s happening to other groups of individuals who are less fortunate,” she said.

Moving forward, Miaskowski encouraged oncology nurses to talk to their patients about symptom burden and loneliness – during the pandemic and beyond.

“I’m going to pressure the clinicians in the room that we need to assess for stress and types of stressors. I think in some cases, it might just be enough to acknowledge that the patient is experiencing stress,” she said. “I know these conversations take time, but I think in the era of COVID-19, the vaccine administration, and post-COVID-19, we need to think about who can have these conversations and when.”

The COVID-19 pandemic increased rates of stress in the general public, adding to that of survivors who may already be feeling anxious. 

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