Interdisciplinary collaboration across the oncology care team is key to improving patient outcomes, according to Darcy Burbage, DNP, RN, AOCN, CBCN.

Burbage, who is also the director-at-large of the Oncology Nursing Society, was selected as one of the featured voices of the 2022 ASCO Annual Meeting and many oncology nurses followed her tweets to track the trending presentations from this year’s meeting. As the only nurse to be selected for this year’s meeting, she helped channel content specific to the oncology nursing community, highlighting practice-changing content surrounding patient-reported outcomes, survivorship, and other aspects of supportive oncology care.

®, Burbage discussed her virtual experience with the 2022 Annual Conference and important nurse takeaways from the meeting.



Which presentations /data to come out of ASCO do you feel will have the largest effect on oncology nursing practice?

 There were so many great presentations, and many will have a huge impact on patient care. For example, the results of the Destiny-04 trial [NCT03734029] are going to be practice changing for a subpopulation of individuals living with metastatic breast cancer. Watching this presentation online and hearing the cheers from those in the audience, gave me chills.

I was also glad to see the voice of the patient being included in presentations on how to expand clinical trial eligibility so that they are more reflective of the populations that we treat, such as expanding the age criteria as well as allowing individuals that may have other health conditions to be included in clinical trials. Without this expansion, we really don’t know how new treatments will benefit as many individuals as possible.

Additionally, I don’t think that we can [underestimate] the impact of the ongoing COVID-19 pandemic on oncology care and on oncology clinicians [and this was clear at this year’s meeting]. 

From the start of the pandemic, patients with cancer were designated as a particularly vulnerable subgroup of the population. The oncology community adapted quickly, pivoting to telehealth to maintain patient continuity, embracing extended-interval dosing strategies, abbreviating radiotherapy schedules, and switching from intravenous to oral chemotherapy regimens. However, we are only beginning to understand the multifaceted impact of the COVID-19 pandemic on cancer incidence, treatment outcomes, and side effects. The conference highlighted the number of oncology clinicians that reduced their hours or left practice and mentioned the large number of nurses that have left the workforce as well. Unless meaningful, system-based changes occur, the shortage will only worsen.

There were some great presentations on cultural humility. What values or applications do you think providers should be taking away from these educational sessions? How does cultural humility play a role in providing quality care?

Cultural humility is essential to provide holistic quality care to all individuals affected by cancer as it values learning from and with our patients. Cultural humility encourages an appreciation and understanding of our unique journeys as its goal is to build a mutually beneficial relationship rather than a provider/patient dynamic. To summarize, cultural humility is a clinical skill requiring curiosity and respect; applying the skill of cultural humility is necessary for culturally competent care, and both are key to providing high quality care.

There has been a lot of conversation surrounding the rising cost of cancer care and financial toxicity following various ASCO presentations. Is financial toxicity a growing problem? What can providers and nurses do to help their patients navigate this toxicity and try to prevent it from becoming worse?

Yes, financial toxicity is a growing concern for our patients. The cost of care itself along with rising deductibles and out of pocket expenses impacts a patient’s quality of life. With newer medications, such as immunotherapy agents, the monthly costs can be thousands of dollars.

All oncology clinicians, nurses, physicians, as well as our administrative staff can help address this by normalizing the financial conversation. For example, some of my patients have questions about the cost of this medication. Because of this, our social worker meets with everyone to review what resources are available. On a federal level, it’s important that oncology nurses continue to advocate for lower insurance premiums and oral parity legislation.

This year’s symptoms and survivorship track showcased data on a variety of topics. Which presentations from this track did you find interesting? How has the focus on symptoms and survivorship grown over the years? Where are their current gaps and where do you think research should continue to focus?

I was glad to see the number of abstracts presented in this category as oncology nurses spend a great deal of time helping individuals manage the long term and late effects of cancer treatment. In particular, I was pleased to see fear of recurrence being addressed.

Individuals living with cancer face a myriad of psychosocial distress throughout the cancer continuum; however, fear of recurrence is one of the most common unmet needs expressed by all of our patients, including those with early-stage cancers and those living with metastatic cancer. Fear of recurrence is associated with increased anxiety which may affect quality of life, and not just that of the individual, but their entire support system. As discussed, we need to assess individuals throughout the cancer continuum, including at the end of active treatment and at all follow-up visits to validate their feelings and provide them with the necessary support.

As the number of individuals living with cancer continues to increase, for example, childhood cancer survivors living well into adulthood, along with the number of individuals diagnosed with cancer that are greater than 65 [years old], there is a need to address comorbidities and how they impact cancer treatment and ongoing effects. For example, how does treatment impact [adverse] effects in individuals with both diabetes and cancer?

In addition, the number of abstract presentations focusing on digital health and patient reported outcomes is another area that continues to increase and where additional collaborative research is needed with our behavioral health colleagues.

Articles

Darcy Burbage, DNP, RN, AOCN, CBCN, discusses the top takeaways from the 2022 ASCO Annual Meeting for oncology nurses.

Burbage Provides Nursing Perspective on 2022 ASCO Meeting

An expanded safety analysis of CheckMate 648 (NCT03143153) illustrated a manageable safety profile with nivolumab (Opdivo) plus chemotherapy, and nivolumab plus ipilimumab (Yervoy), as frontline treatment for esophageal squamous cell carcinoma (ESCC).The analysis, which was presented during the 

, also highlighted key differences in median onset and resolution times between the dual immunotherapy and chemotherapy combinations, as well as the number of patients receiving immune modulating medications (IMM) at a 1-year follow-up.

 nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy or ipilimumab for unresectable advanced or metastatic ESCC based on 

. Overall, the study demonstrated that these frontline combinations may be a viable method of extending overall survival in all-randomized patients with ESCC as well as those with a tumor cell PD-L1 score of at least 1%, compared with chemotherapy alone.

In addition, the nivolumab plus ipilimumab and nivolumab plus chemotherapy regimens, yielded superior time to second disease progression (PFS2) and demonstrated greater efficacy in prolonging duration of response compared with chemotherapy, regardless of tumor cell PD-L1 score. Deep responses were reported across all 3 treatment regimens.

The updated data confirmed the adverse event (AE) profiles were consistent with previously reported safety outcomes of the individual components at similar doses. Further, 2% or less of patients treated with nivolumab plus chemotherapy and 6% of less of patients treated with nivolumab pus ipilimumab developed grade 3/4 TRAEs with potential immunologic etiology.

Across the 3 treatment arms, the percentage of patients who experienced a TRAE of any-grade in the nivolumab/chemotherapy (n = 310), nivolumab/ipilimumab (n = 332), and chemotherapy alone arms (n = 304) were 96%, 80%, and 90%, respectively. Among these, the percentage of grade 3/4 TRAEs was 47%, 32%, and 36%.

The percentage of TRAEs leading to treatment discontinuation across the 3 arms was 34%, 18%, and 19%, respectively, and the number of treatment-related deaths was 5 (2%), 8 (2%), and 6 patients (2%), respectively.

Data on TRAEs with potential immunologic etiology showed that any-grade endocrine-related toxicities occurred in 12%, 27%, and fewer than 1% of patients receiving nivolumab/chemotherapy, nivolumab/ipilimumab, and chemotherapy alone, respectively. The rates of any-grade gastrointestinal-related toxicities were 21%, 12%, and 15%; hepatic toxicities were 10%, 13%, and 4%; pulmonary toxicities were 6%, 8%, and fewer than 1%; and renal toxicities were 24%, 2%, and 19%, respectively. Skin-related toxicities were the most common, the rate of these toxicities in the nivolumab/ipilimumab arm (34%) and occurred at rates of 17% and 4% in the nivolumab/chemotherapy and chemotherapy alone arms, respectively.

Among patients who received nivolumab plus chemotherapy and experienced a non-endocrine TRAE with potential immunological etiology, most were resolved (57%-91% across organ categories). The median time to resolution had a range of 1.5 to 17.1 weeks.

Similarly, among patients receiving received nivolumab plus ipilimumab who experienced a non-endocrine TRAE with potential immunological etiology, most were resolved (63%-95%) and the median time to resolutions were between 2.9 to 12.1 weeks.

®, CheckMate 648investigator Ken Kato MD

PhD, medical oncologist at the National Cancer Center of Tokyo, said the median onset time differed between the chemotherapy/immunotherapy and dual immunotherapy combinations.

“Time-to-onset was [accelerated] in the IO [immunotherapy] arm,” Kato said. “For example, with endocrine-related toxicities, the median onset time was 13.0 weeks [range, 5.0-100.0] with the nivolumab/chemotherapy combination. On the other hand, in the nivolumab/ipilimumab combination [arm], the median onset time was 8.2 weeks [range, 1.9-72.9].”

This trend was also observed across other immune-related toxicities. Hepatic toxicities, for example, had a median onset time of 5.0 weeks (range, 1.0-5.0) in the ipilimumab combination arm vs 7.9 weeks (range, 0.3-84.1) in the chemotherapy combination arm. For pulmonary toxicity, the median onset time between the 2 arms was 11.9 weeks (range, 1.9-72.3) vs 31.2 weeks (range, 5.0-85.1), respectively; for renal toxicities, median onset time was 7.1 weeks (range, 1.1-47.1) vs 10.1 weeks (range, 0.7-60.7); and skin-related toxicities had a median onset time of 3.9 weeks (range, 0.1-54.3) vs 5.9 weeks (range, 0.1-61.1).

Gastrointestinal toxicities were the exception in this data set. The median onset time with dual immunotherapy was 9.1 weeks (range, 0.6-50.3) nearly doubling that of the nivolumab/chemotherapy combination at 5.1 weeks (range, 0.3-53.1).

Resolution Analysis + Immune Modulating Therapy

Although the median resolution time for TRAEs among patients in both nivolumab combination treatment arms was not reached, most other immune-related TRAEs did resolve by the data cutoff.

Among those treated with nivolumab plus chemotherapy, 91% of gastrointestinal toxicities were resolved (n = 58/64) at a resolution time of 1.5 weeks (range, 0.1-65.9); 90% of hepatic toxicities were resolved (n = 28/31) at a median resolution time of 2.4 weeks (range, 0.4-24.0); 67% of pulmonary were resolved (n = 12/18) at a median time of 12.1 weeks (range, 1.0-39.9); 57% of renal were resoled (n = 42/74) at a median of 17.1 weeks (range, 0.4-128.1); and 76% of skin toxicities were resolved (n = 41/54) at a median resolution time of 7.1 weeks (range, 0.1-157.0).

The percentage of patients receiving IMM, including corticosteroids, with gastrointestinal, hepatic, pulmonary, renal, or skin TRAEs was 11%, 6%, 50%, 70%, 7%, and 43%, respectively. The percentage of patients with endocrine-related toxicity receiving an IMM was 22%.

Among those treated with nivolumab plus ipilimumab, 95% of gastrointestinal toxicities were resolved (n = 36/38) at a resolution time of 2.9 weeks (range, 0.3-79.1); 88% of hepatic toxicities were resolved (n = 37/42) at a median resolution time of 5.1 weeks (range, 1.1-30.9); 65% of pulmonary were resolved (n = 17/26) at a median time of 12.1 weeks (range, 1.0-119.3); 63% of renal were resoled (n = 5/8) at a median of 9.6 weeks (range, 0.7-142.3); and 70% of skin toxicities were resolved (n = 77/110) at a median resolution time of 11.4 weeks (range, 0.3-146.6).

The percentage of patients receiving IMM among these organ groups was 26%, 31%, 35%, 50%, and 51%, respectively. The percentage of patients with endocrine-related toxicity on IMM was 39%.

Overall, no new safety developments were identified, and the immunological responses were deemed manageable by investigators. These data, in combination with the promising survival data, support the combinations’ role in treating ESCC.

Chau I, Doki Y, Ajani JA, et al. Nivolumab + chemotherapy or ipilimumab vs chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma: expanded efficacy and safety analyses from CheckMate-648. 

 2022;40(suppl 16):4035. doi:10.1200/JCO.2022.40.16_suppl.4035

Data from the CheckMate 648 trial informed the FDA’s recent approval of 2 nivolumab combinations for esophageal squamous cell carcinoma. A 1-year follow-up analysis highlighted key safety and time-to-event data surrounding immune-related toxicities. 

Expanded Safety Analysis from CheckMate 648 Shows Tolerability with Frontline Nivolumab Combinations in ESCC

Buprenorphine may be an effective pain management strategy for various populations of patients with cancer, according to palliative care experts Mary Lynn McPherson, PharmD, BCPS, FAAHPM; and Amy A. Case, MD, FAAHPM.

 The agent’s unique pharmacology, and clinical utility and safety data, make it a preferable choice over traditionally used opioids.

McPherson, who is a professor at the University of Maryland, Baltimore, and executive director of the Advanced Post-Graduate Education in Palliative Care, Graduate Studies in Palliative Care, and Online Graduate Studies in Palliative Care programs, and Case, who is the chair of Supportive and Palliative Care at Roswell Park Comprehensive Cancer Center, recently participated in an invited speaker session titled “Why Consider Buprenorphine for Cancer-Related Pain?” at the 2022 Supportive Care in Cancer Annual Meeting.

The oral bioavailability associated with buprenorphine is low. Therefore, it is not swallowed as a pill. It is taken sublingually or through a patch that should be rotated to a different site and then returned to the original site every 21 days according to the package insert.

“It is a really good option [for] those with who cannot swallow,” Case said.

“Generally, we use it on the upper body and areas where there is not a large amount of subcutaneous fats,” she explained.

Moreover, buprenorphine functions differently compared with traditional μ-opioid receptor agonists, explained McPherson. The agent binds to μ, δ, κ, and opioid receptor-like 1 (ORL1). It has a very high binding affinity to the μ receptor, as well as with the δ and κ receptors, but a lower binding affinity for ORL1. However, it is a partial μ agonist and not a full μ-opioid agonist.

As a partial agonist, buprenorphine has less μ-receptor signaling, which may result in fewer opioid-related adverse events. However, this does not mean buprenorphine is not an effective analgesic. It has a higher binding affinity compared with most full μ-opioid agonists, suggesting that it is a very effective pain management option.

Several studies with large numbers of patients with cancer have documented that pain management with buprenorphine is effective, Case said. For example, in one study, 85% of patients reported their pain control to be “good” or “very good” and 48% of patients reported improvement in sleep quality.

“A lot of our patients in palliative care or supportive care in oncology have issues with sleep,” Case explained. “[Buprenorphine,] has been shown to be equivalent to other traditional used opioids [in managing this symptom].”

It has also demonstrated a benefit for neuropathic pain and successfully blocks secondary hyperalgesia from central sensitization. Its analgesic benefit is thought to be comparable to morphine, hydromorphone, oxycodone, fentanyl, and methadone.

Furthermore, its high potency and slow dissociation rate allows for effective treatment at lower doses, Lin added.

Buprenorphine has less beta-arrestin activity than traditional opioids once it binds

, Case explained. Beta-arrestin is linked with negative responses such as endocytosis, physical dependency, respiratory depression, and constipation.

In addition, buprenorphine is associated with less cognitive dysfunction than with other opioids, making it a viable choice for elderly patients. “There is less impairment [compared] with equal doses of morphine,” Case said. “Several studies have shown improved sleep, pain, quality of life in the elderly [who receive buprenorphine].”

Notably, the pharmacokinetics are not altered with age, so there are no required dose reductions for elderly patient populations, and it is the only opioid that is not associated with risk of fracture, although Case noted that there is insufficient literature on this risk.

Across all populations, buprenorphine represents a potentially safer alternative for patients at risk for dependency disorders, since it does not induce euphoria, and is therefore associated with reduce abuse liability. It is safe in patients with renal and liver impairment, although for patients with severe liver impairment, a 50% dose reduction is advised because the drug is metabolized by the liver. It is also associated with a reduced risk of respiratory depression.

Finally, because the drug is a κ antagonist, patients may have less anxiety, lytic effects, depression, or suicidal tendencies compared with traditional opioids.

 This may also limit the addictive potential.

“[There are] some papers out there showing that up buprenorphine is actually used as a treatment for depression,” Case said.

Case acknowledged that some providers may find it difficult to get insurance companies to cover buprenorphine. However, in her experience, most companies will if presented with data on the drugs’ efficacy.

In 2019, the US Department of Health and Human Services published their Pain Management Best Practices Document. The document lists the following recommendations:

Recommendation 4a: Make buprenorphine treatment for chronic pain available for specific groups of patients and include buprenorphine in third-party payer and hospital formularies.

Recommendation 4b: Encourage CMS and private payers to provide coverage and reimbursement for buprenorphine treatment, both for opioid use disorder and for chronic pain. Encourage primary use of buprenorphine rather than use only after failure of standard μ agonist opioids such as hydrocodone or fentanyl, if clinically indicated.

Recommendation 4c: Encourage clinical trials using buprenorphine for chronic pain to better understand indication, usage and dosage.

“When the insurance companies give me a hard time about, I send [the recommendations] to them and clog up their fax machines and then they cover it,” Case concluded.

McPherson ML, Case AA. Why consider buprenorphine for cancer-related pain? Presented at: 2022 Supportive Care in Cancer Annual Meeting; June 23-25, 2022; Toronto, Ontario. 

Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. 

. 2020;9(1):41-54. doi:10.1007/s40122-019-00143-6

Pain management best practices best practices inter-agency task force report, updated gaps, inconsistencies, and recommendations. US Department of Health and Human Services. Accessed June 24, 2022. 

Mary Lynn McPherson, PharmD, BCPS, FAAHPM, and Amy A. Case, MD, FAAHPM, argue that buprenorphine should play a larger role in cancer-related pain management because of its unique pharmacology and consequent safety profile.  



Experts Make the Case for Buprenorphine Use in Cancer-Related Pain Management

Cancer survivors who experience both frontal and occipital late alopecia following cytotoxic or endocrine therapy may derive clinical benefit with oral minoxidil, according to data from a study at Memorial Sloan Kettering Cancer Center (MSK), which were presented during the 2022 ASCO Annual Meeting.

Overall, hair and follicle densities increased by approximately 20% across all tested populations, and 74% of patients showed clinical improvement. Moreover, no patients required treatment discontinuation because of adverse events (AEs).

Alopecia is a common AE with approximately 65% of patients who undergo chemotherapy experiencing some degree of alopecia.1 Furthermore, 58% of patients with cancer report that hair loss is the most traumatic component of receiving chemotherapy, and 1 in 7 patients would consider declining chemotherapy because of fear of hair loss. 

Late alopecia was defined by investigators as the incomplete hair regrowth 6 months following the completion of endocrine therapy or from the initiation of endocrine therapy. This longer-lasting AE reportedly affects between 25% to 30% of survivors.

Scalp cooling is the only known prevention technique, and treatment options include scalp directed topical steroids, compounded topical minoxidil finasteride, intralesional steroids, or systematic oral low dose minoxidil. Oral minoxidil at a dose of 10 to 100 mg daily is currently FDA approved as an antihypertensive agent, but it has been used in low doses off label to treat alopecia at a dosage of 0.25 to 5 mg daily.

Investigators at MSK assessed women with late alopecia who received oral minoxidil at a dose of 1.25 mg daily between January 2018 and May 2021.The efficacy of minoxidil was assessed via standardized photography, and responses were quantified via trichosocpy (HairMetrix).

Results from 42 trichoscopy assessments conducted before and after a median of 91 days (interquartile range, 136) on oral minoxidil showed that the median percentage change in hair density (hairs/cm2) was 20.4% (

= .008) in patients with frontal alopecia and 21.4% (

 = .004) in patients with occipital alopecia, respectively. Similarly, the changes in follicular density (follicles/cm2) were 22.5% (

 = .005), respectively. Hair shaft diameter between the 2 groups was –2.0% (

The literature shows that the most common AEs associated with this treatment include hypertrichosis, lightheadedness, and fluid retention. Prospective, controlled studies are still needed to validate these findings, study authors concluded.

Overall, results from this study demonstrate the importance of symptom management in survivorship care, according to experts.

“Treating late toxicities [is] the bread and butter of survivorship,” Lidia Schapira, MD, FASCO, Professor of Oncology at Stanford University with a specialization in survivorship, said in a discussion of the poster. “Patients are often left to manage these by themselves. The idea of helping patients understand, self-manage, and become better at handling toxicities, [starting] from the first day in the hospital, is a very important concept.”

The key moving forward will be expanding these efforts to populations that have less supportive resources currently available, Schapira added.

“Supportive services such as onco-dermatology and supportive dermatology are available at major cancer centers, and I absolutely am delighted to see our colleagues at Memorial Sloan Kettering continue to find solutions for some of these festering problems,” she said. “The question is how do we scale [these efforts] and how do we bring some of these advances in survivorship care to communities that are less well resourced?”

Kuo AM, Reingold RE, Ketosugbo KF, et al. Oral minoxidil for the treatment of late alopecia in cancer survivors. 

2022;40(suppl 16):12022. doi:10.1200/JCO.2022.40.16_suppl.12022

Results of a single-center study presented at the 2022 ASCO Annual Meeting showed that oral minoxidil may be effective in treating late alopecia. Moving forward, these efforts in survivorship care will need to be expanded to less resourced areas, experts said.  

Oral Minoxidil Demonstrates Efficacy in Treating Later Stage Alopecia in Cancer Survivors

The combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) has secured accelerated approval from the FDA for the treatment of adult and pediatric patients aged 6 years and older who have 

 V600E–mutated, unresectable or metastatic solid tumors, and whose disease has progressed following all other satisfactory treatment options.

The regulatory decision was supported by clinical efficacy and safety data observed in 3 clinical trials. In the phase 2 ROAR basket study (NCT02034110) and arm H of the NCI-MATCH study (NCT02465060), the doublet resulted in overall response rates of up to 80% in patients with 

 V600E–mutated solid tumors, including high- and low-grade glioma, biliary tract cancer and select gynecological and gastrointestinal cancers.

 Moreover, an additional study, Study X2101 (NCT02124772), demonstrated the clinical benefit and acceptable toxicity profile of the combination in pediatric patients.

“The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple 

-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” Vivek Subbiah, MD, principal investigator and associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, stated in a press release. “Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors.”

The multi-cohort, multicenter, non-randomized, open-label ROAR trial included adult patients with selected tumors harboring 

V600E mutation; this included those with high-grade glioma (n = 45), biliary tract cancer (n = 43), low-grade glioma (n = 13), adenocarcinoma of small intestine (n = 3), gastrointestinal stromal tumor (n = 1), and anaplastic thyroid cancer.

Patients were enrolled based on local assessments of 

 mutation was confirmed via central laboratory in 93 of 105 patients.

Arm H of the single-arm, open-label NCI-MATCH study also enrolled patients with a 

 V600E mutation. Here, patients with melanoma, thyroid cancer, or colorectal cancer were excluded, and 

 V600E mutational status for enrollment was determined either by central or local laboratory test.

The study included adult patients with solid tumors such as gastrointestinal tumors (n = 14), lung cancers (n = 7), gynecologic or peritoneal tumors (n = 6), central nervous system tumors (n = 4), and ameloblastoma of mandible (n = 1).

Among the 131 patients enrolled ito both trials, the median age at baseline was 51 years, with 20% of patients aged 65 years or older. Moreoverf, 56% of patients were female; 85% were White, 9% were Asian, and 3% were Black. The majority of patients (56%) had an ECOG performance status of 1, 37% had a status of 0, and 6% had a status of 2. Of the 131 patients, 90% received prior systemic therapy.

Additional data from these trials showed that the objective response rate (ORR) achieved with the combination in those with biliary tract cancer (n = 48) was 46% (95% CI, 31%-61%), with a median duration of response (DOR) of 9.8 months (95% CI, 5.3-20.4). In those with high-grade glioma (n = 48), the ORR was 33% (95% CI, 20%-48%), with a median DOR of 13.6 months (95% CI, 5.5-26.7).

In those with low-grade glioma (n = 14), the ORR achieved with the doublet was 50% (95% CI, 23%-77%), with a DOR ranging from 6 months to 29 months. Moreover, dabrafenib plus trametinib resulted in ORRs of 80% and 50% in those with low-grade serous ovarian cancer (n = 5) and those with adenocarcinom of the small intestine (n = 4), respectively; the median DORs ranged from 12 months to 42 months, and 7 months to 8 months, respectively.

The multicenter, open-label, multiple cohort Study X2101 included pediatric patients with refractory or recurrent solid tumors. Part C was a dose escalation of dabrafenib in combination with trametinib in patients whose tumors harbored a 

 V600E mutation. Part D was a cohort expansion phase of dabrafenib in combination with trametinib in patients with low-grade glioma and a 

The major efficacy outcome measure was ORR per ndependent review committee assessment and by RANO criteria. The efficacy of the doublet was examined in a total of 48 pediatric patients; 34 of these patients had low-grade glioma and 2 had high-grade glioma. For those with 

 V600E–mutated low-grade glioma and high-grade glioma in parts C and D, respectively, the median age was 10 years (range, 1-17) and 50% were male. Moreover, 75% of patients were White, 8% were Asian, and 3% were Black. Fifty-eight percent of patients had a Karnofsky/Lansky performance status of 100.

Eighty-three percent of patients previously underwent surgery, 2.8% had prior external beam radiotherapy, and 92% previously received systemic therapy. Data showed that the combination elicited an ORR of 25% (95% CI, 12%-42%). For the 9 responders, the DOR was 6 months or longer for 78% of patients and 24 months or longer for 44% of patients.

The toxicity profile of the combination observed in these studies was consistent with the known profile in other approved indications.

“Tackling cancer is complex, which is why it is so important that we continue to follow the science as we pursue meaningful advances and new approaches to treating cancer,” Reshema Kemps-Polanco, head of Novartis Oncology US, added in the press release. “We are grateful to the patients, and to the multitude of individuals and teams working together to make this latest approval possible as we strive to do more for more people living with cancer.”

Novartis Tafinlar + Mekinist receives FDA approval for first tumor-agnostic indication for BRAF V600E solid tumors. News release. Novartis Pharma AG. June 22, 2022. Accessed June 22, 2022. https://bit.ly/3tW25BN

Tafinlar. Prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. Accessed June 22, 2022. https://bit.ly/3HM4IMv

This article was originally published on OncLive as “FDA Approves Dabrafenib Plus Trametinib for BRAF V600E–Mutated Unresectable or Metastatic Solid Tumors”

The FDA approval of dabrafenib plus trametinib for BRAF V600E–mutated unresectable or metastatic solid tumors highlights a potential need for routine BRAF testing in clinical practice, experts say.  

FDA Grants Accelerated Approval to Dabrafenib Plus Trametinib for BRAF V600E–Mutated Solid Tumors

Roxadustat (Evrenzo), increased hemoglobin counts in patients with chemotherapy-induced anemia, according to findings from an open-label, phase 2 study which was presented at the 2022 ASCO Annual Meeting. Patients received starting doses of either 2.0 or 2.5 mg/kg and investigators reported that those who received initial doses of 2.5 mg/kg experienced more immediate hemoglobin increases and required fewer red blood count infusions than their counterparts.

The median time to a hemoglobin increase of at least 1.0 g/dL, 1.5g/dL, and 2.0 g/dL among patients who began treatment with a 2.5 mg/kg dose was 30 days, 43 days, and 57 days, respectively. In comparison, the median time to the same hemoglobin increases in patients who started with the 2.0-mg/kg dose was 44 days, 71 days, and 105 days, respectively. Overall, the median time to increase among all patients was 41 days, 46 days, and 71 days, respectively.

Moreover, between weeks 5 and 16 of treatment, 11.1% of patients starting roxadustat at 2.5 mg/kg (n = 31) required a red blood cell transfusion compared with 20.7% of those starting with 2.0 mg/kg (n = 61).

“Up to 90% of patients receiving myelosuppressive chemotherapy develop anemia, and it is exacerbated by repeated treatment cycles due to cumulative toxicity,” the study authors wrote in a poster. “Chemotherapy-induced anemia management options are suboptimal and alternative treatment options are needed. Roxadustat, on oral hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin by stimulating endogenous erythropoietin synthesis and improving iron kinetics.”

The single-arm, proof-of-concept study enrolled patients with nonmyeloid malignancies who were eighteen years or older and had chemotherapy-induced anemia, defined as hemoglobin levels less than or equal to 10 g/dL. Patients were enrolled between August 2019 and April 2021. A red blood cell transfusion or prior treatment with an erythropoietin-stimulating agent within 4 weeks of enrollment were grounds for exclusion.

Patients received oral roxadustat 3 times per week for up to 16 weeks, with dose adjustments every 4 weeks based on hemoglobin levels and hemoglobin changes. Investigators noted that most patients required a dose increase at week 5, and an amendment to the trial protocol was established in May 2020 that patients would start with 2.5 mg/kg instead of 2.0 mg/kg.

Among patients who began treatment at 2.0 mg/kg dosage, there were larger number of women than men (53 vs 39, respectively). Most study participants also had a C-reactive protein greater than the upper limit of normal. The most common malignancies included breast (22.6%) and pancreatic cancer (19.4%). Among patients who started treatment with the 2.5 mg/kg dose, a larger percentage had received treatment with platinum-based chemotherapy (50.8% vs 32.3% at the 2.0-mg/kg dose). The most common malignancies in this cohort were gastrointestinal tract (18.0%), lung (13.1%), or ovarian cancer (13.1%).

Iron replete was defined as transferrin saturation (TSAT) greater than or equal to 30% and ferritin equal to or greater than 100 µg/L. Iron nonreplete was defined as TSAT of less than 20% and ferritin less than 100 µg/L.

Overall, the mean maximum change in hemoglobin throughout the 16 weeks was 2.8 g/dL and 2.0 g/dL in iron replete vs nonreplete populations, respectively. Between baseline and week 16, 60.7% of patients experienced a hemoglobin increase equal to or greater than 2.0 g/dL; this change was observed in 61.8% and 58.8% of iron-replete patients and iron nonreplete populations, respectively.

The 2 starting doses had a similar proportion of patients who experienced hemoglobin increases equal to or greater than 1.0, 1.5, and 2.0 g/dL. Also, a subgroup analysis revealed that between the 2 starting doses, the mean maximum hemoglobin increases ranged between 1.4–2.9 g/dL and 2.3–2.6 g/dL in major tumor and chemotherapy types, respectively.

Safety data were limited by the absence of a placebo group; however, the observed adverse events (AEs) were consistent with those typically seen in a diverse group of patients with cancer undergoing concomitant chemotherapy, and no deaths were attributed to the investigational agent. In the overall treatment population (n = 92), the number of treatment-emergent AEs (TEAEs) was 85 (92.5%). There were 17 incidences (18.5%) of TEAEs leading to treatment discontinuation. Further 17 TEAEs (18.5%) were related to the study drug, 14 (15.2%) cases of deep vein thrombosis and 9 (9.8%) of pulmonary embolism were reported.

The frequency of TEAEs and severe TEAEs were comparable between the 2 starting doses. In the 2.0 mg vs 2.5 mg/kg cohorts, the number of any TEAEs was 31 (100%) and 54 (88.5%), respectively. The number of TEAEs resulting in treatment discontinuation was 6 (19.4%) vs 11 (18%), respectively. In terms of specific TEAEs, cases of deep vein thrombosis cases were reported in 5 (16.1%) vs 9 (14.8%) patients, respectively, and the number of pulmonary embolism cases was 3 (9.7%) vs 6 (9.8%). Overall, 6 (19.4%) vs 11 (18%) incidences were related to roxadustat.

In terms of severe TEAEs, 14 (45.2%) vs 26 (42.6%) events were reported in the 2.0-mg/kg and 2.5-mg/kg cohorts, respectively. The number of severe TEAEs leading to treatment discontinuation was 5 (16.1) vs 10 (16.4), respectively.

Glaspy J, Gabrail NY, Locantore-Ford P, et al. Open-label, phase 2 study of roxadustat for treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies. 

 2022;40(suppl 16):12085. doi:10.1200/JCO.2022.40.16_suppl.12085

Phase 2 findings found that patients with chemotherapy-induced anemia experienced increases in hemoglobin following treatment with roxadustat. 

Roxadustat Increases Hemoglobin Counts in Patients With Chemotherapy-Induced Anemia

Starting the conversation is a simple, yet important, step to draw attention to DEI—diversity, equity, and inclusion—in oncology nurse leadership, according to Aliènne Salleroli, MS, BSN, RN, OCN.

Salleroli, an assistant patient services manager at Yale-New Haven Health Smilow Cancer Hospital, and cochair of the Yale New Haven Hospital Diversity, Equity, and Inclusion Nursing Task Force, recently spoke on the topic of how racial diversity within oncology leadership is linked with positive outcomes at the 47th Annual Oncology Nursing Society Congress.

®, Salleroli explains that although opening dialogue can be uncomfortable, it yields important results.

“Leadership needs to understand that this is going to be an uncomfortable conversation and part of leadership is becoming comfortable with the uncomfortable,” she said. “But having these conversations [is] actually what bridge[s] that gap. Discussing things like micro-aggressions, implicit biases, language being used… that’s what brings [individuals] together.”

Open dialogue is key to establishing unity across an organization, Salleroli said, adding that these conversations can also inspire local change. For example, once leadership starts the conversation, heads of other teams can bring that information down to their home departments and perpetuate a domino effect.

“We need to walk before we can run,” she concluded.

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Aliènne Salleroli, MS, BSN, RN, OCN, underscores the importance of open dialogue surrounding diversity, equity, and inclusion in oncology leadership. 

Aliènne Salleroli on Starting the DEI Conversation in Oncology Nursing

Music-listening interventions (MLIs) are a form of complementary and integrative treatment that medical professionals may be unaware of. However, my colleagues at the Michigan State University College of Nursing and I are tackling research that suggests music—a fixture in many people’s daily lives—may possess a nausea-reducing capability.

MLIs have already shown considerable effectiveness in managing other symptoms. For example, the National Comprehensive Cancer Network has labeled music as an acceptable treatment modality to treat anticipatory nausea and vomiting related to chemotherapy, so long as the music is prescribed in conjunction with typical pharmaceuticals.

Furthermore, the American Pain Society and the American Society of Regional Anesthesia and Pain Medicine have both endorsed music for its mitigating effects in the setting of postoperative pain.

 In addition, the c linical practice guidelines provided by the Society for Integrative Oncology also endorse music for patients with breast cancer in the setting of anxiety, mood disturbances, and pain.

In all cases, these endorsements came as a result of careful review of the evidence base for MLIs. If pain, anxiety, and mood all can be positively impacted through the incorporation of an MLI—why not chemotherapy-induced nausea?

This research began with a systematic review of the available literature, scouring databases for all prior studies that examined an MLI as treatment for chemotherapy-induced nausea.

This search identified 10 relevant studies across the past 30 years. However, they had a variety of designs, making comparisons between them difficult. Some studies paired music with other interventions, which made it difficult to discriminate what percentage each intervention was contributing to nausea reduction. Variations in timing (when the MLI was delivered and when the effect on nausea was measured) also raised questions.

Moreover, in the world of pharmaceuticals, a drug’s half-life determines how quickly its effects fade. However, variations in how MLIs were timed to intervene on nausea illuminated the fact that MLI’s half-lives are not well understood. It remains unclear whether half-lives even exist for MLIs. Overall, the overarching body of existing literature highlighted a need for more nuanced research.

The greatest uncertainty that remains with MLIs has to do with mechanism of action. Although MLIs have previously demonstrated the potential to relieve nausea, investigators do not yet understand how the brain physiology permits this.

One possible answer to this question comes from surprising research unrelated to chemotherapy-induced nausea. In 2000, Evers and Suhr

 published a study in which healthy participants listened to music that participants rated as “pleasant” and music that participants identified as “unpleasant.” In this study, the concentration of serotonin in blood platelets was measured at baseline (before any music), after the unpleasant music, then after the pleasant music. The release of serotonin from platelets was significantly less after the pleasant music intervention than what was measured after the unpleasant music. These findings connected to chemotherapy-induced nausea by way of its serotonin effects. After chemotherapy, this neurotransmitter becomes a major contributor to the sensation of nausea. This also explains the pharmacologic rationale for prescribing drugs that antagonize serotonin’s ability to bind to receptors at the postsynapse of neurons in the central nervous system.

This interesting physiologic possibility initiated a pilot study that yielded encouraging results. Twelve patients were asked to engage in a 30-minute MLI whenever they felt the need to take their antiemetic medication as needed, beginning on the day of chemotherapy administration and continuing through day 5. Participants used ordinal scales to rate their nausea severity and their distress level before the MLI and again immediately upon completion. Platelet serotonin levels were not drawn due to cost. In total, 66 MLIs were engaged at various points within the 5-day nausea window. The analysis showed a significant reduction in both nausea severity and patient distress, which is an encouraging finding in a pilot study and worth replicating in a larger randomized control trial.

This larger trial will have several refinements. First, a control group using a nonmusic intervention will reveal what percentage of the antinausea effect was attributable to the MLI and what percentage was attributable to medication alone. Creating study groups by time (5-minute MLI and 10-minute MLI) will allow subgroup analysis by dose, which is something not often done in MLI research. Finally, strict attention to competing auditory stimuli (other sounds in the room) through noise-cancelling headphones will help participants more fully engage with the MLI. 

Strategically using music listening to produce improved physiologic states is not new, but its scientific activity is gaining momentum. Work in chemotherapy-related nausea may inspire other investigators to think about MLIs in the setting of other nausea forms, such as pregnancy-induced nausea or postoperative/postanesthesia nausea. As the research builds, the day may come when the oncology nurse delivers acetaminophen alongside 20 mg of Mozart.

NCCN. Clinical Practice Guidelines in Oncology. Antiemesis, version 2.2022. Accessed April 23, 2022.

 https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf

Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. 

. 2016;17(2):131-157. Published correction appears in 

Lyman GH, Greenlee H, Bohlke K, et al. Integrative therapies during and after breast cancer treatment: ASCO endorsement of the SIO clinical practice guideline. 

. 2018;36(25):2647-2655. doi:10.1200/JCO.2018.79.2721

Evers S, Suhr B. Changes of the neurotransmitter serotonin but not of hormones during short time music perception. 

. 2000;250(3):144-147. doi:10.1007/s004060070031

Kottschade L, Novotny P, Lyss A, Mazurczak M, Loprinzi C, Barton D. Chemotherapy-induced nausea and vomiting: incidence and characteristics of persistent symptoms and future directions NCCTG N08C3 (Alliance). 

. 2016;24(6):2661-2667. doi:10.1007/s00520-016-3080-y

A Michigan State University investigator is preparing to expand on an encouraging pilot study that used a music-listening intervention to influence chemotherapy-induced nausea.

Prescribing 20 mg of Mozart for Chemotherapy-Induced Nausea

Frontline treatment with panitumumab (Vectibix) plus chemotherapy resulted in improved overall survival (OS) outcomes for patients with 

 wild-type metastatic colorectal cancer (mCRC), said Takayuki Yoshino, MD, PhD, in a presentation of the findings from the phase 3 PARADIGM trial (NCT02394795).1 The data, which were presented in a press briefing at the 

 revealed that the combination was superior to bevacizumab (Avastin) and chemotherapy in this patient population.

Results showed an improvement in overall survival (OS) in the panitumumab arm of the trial compared with the bevacizumab arm in both the left-sided primary tumor and overall mCRC populations.

“Panitumumab and the modified FOLFOX6 [regimen] demonstrated longer survival [than] ever reported in the first-line metastatic colorectal cancer phase 3 studies,” said Yoshino, who is chief the Department of Gastrointestinal Oncology and deputy director of the National Cancer Center Hospital East in Chiba, Japan, during the press briefing.

Retrospective data pooled from 6 randomized trials (CRYSAL, FIRE-3, CALGB 80405, PRIME, PEAK, and 20050181) have suggested that patients with 

 wild-type mCRC who have primary left-sided disease (descending colon, sigmoid colon, rectosigmoid, and rectum) benefit more from anti-EGFR therapy in combination with chemotherapy than anti-VEGF therapy plus chemotherapy.2

“PARADIGM is the first prospective study to test the superiority of panitumumab over bevacizumab plus standard chemotherapy in patients with 

 wild-type [mCRC],” Yoshino explained.

Panitumumab was the first fully human EGFR-directed monoclonal antibody approved by the FDA for the treatment of patients with mCRC in September 2006. The FDA also approved an indication for panitumumab in June 2017 as treatment for patients with 

PARADIGM was a randomized, open-label, multicenter phase 3 study that enrolled 823 patients with 

 wild-type mCRC who had unresectable disease and no prior chemotherapy. They were randomized 1:1 to receive either panitumumab and mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) or bevacizumab and mFOLFOX6. All patients were treated until disease progression, intolerable toxicity, curative resection, or patient withdrawal.1

The primary end point was OS in the left-sided mCRC population, and if OS benefit was significant in this group, it would also be analyzed in the overall population of both left-sided and right-sided mCRC.

In the left-sided population, the median OS in patients receiving panitumumab and mFOLFOX6 (n = 312) was 37.9 months (95.798% CI, 34.1-42.6) compared with 34.3 months (95.798% CI, 30.9-40.3) in the bevacizumab and mFOLFOX6 arm (n = 292) (stratified HR, 0.82; 95.798% CI, 0.68-0.99; 

 value was less than .04202, it was considered significant.

The median OS was 36.2 months (95% CI, 32.0-39.0) with panitumumab and chemotherapy compared with 31.3 months (95% CI, 29.3-34.1) with bevacizumab and chemotherapy (stratified HR, 0.84; 95% CI, 0.72-0.98; 

 = .030) among 802 evaluable patients with 

 wild-type mCRC in the overall trial. The 

 value was under .05, so the investigators considered the comparison significant as well.

According to Yoshino, these results established a standard first-line combination regimen for patients with 

 wild-type, left-sided metastatic colorectal cancer.

Phase 3 findings showed that panitumumab plus mFOLFOX significantly improved overall survival in patients with RAS wild-type metastatic colorectal cancer.

Gastrointestinal Cancer