We rounded up 5 stories from the 2022 ASCO Annual Meeting that are of most value to oncology nurses.

This year’s meeting highlighted advances in ovarian clear cell carcinoma, as well as significant differences in tolerability among different approved PARP inhibitors. Investigators also took an inside look at the driving factors behind medication non-adherence in older patients who were prescribed oral therapies, the impact of ribociclib dose reductions on overall survival in patients with hormone receptor–positive, HER2-negative, advanced breast cancer, and whether or not Vitamin D has prognostic value in determining a patient’s risk of developing chemotherapy-induced peripheral neuropathy.

Real-World Data Identify Significant Differences in Tolerability Among Approved PARP Inhibitors in Ovarian Cancer

Patients with ovarian cancer treated with FDA-approved PARP inhibitors had significant differences in the incidence of clinically relevant adverse events (AEs), according to results of a real-world analysis presented at the 2022 ASCO Annual Meeting.

The findings highlight differences in tolerability, use, and dose modifications associated with olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca) for patients treated with ovarian cancer between January 1, 2017, and December 31, 2020.

Crude results found that clinical events of interest (CEIs) were generally stable across calendar years, but were lower with olaparib vs niraparib for most years. Furthermore, the risk of any CEI, as well as time to PARP dose decrease and PARP dose discontinuation, was significantly different with niraparib compared with olaparib and with niraparib compared with rucaparib.

In a multivariable Cox regression analysis, the adjusted hazard ratio (HR) of any CEI with niraparib vs olaparib was 1.34 (95% CI, 1.19-1.52; 

 < .001), compared to 1.13 with rucaparib vs olaparib (95% CI, 0.96-1.33; 

 = .1318) and 1.19 with niraparib vs rucaparib (95% CI, 1.01-1.40; 

 = .0385). The risk of all-cause hospital admission with niraparib vs olaparib was 1.46 (95% CI, 1.15-1.84; 

 = .0016), compared to 1.38 with rucaparib vs olaparib (95% CI, 1.03-1.86; 

 = .0301) and 1.05 with niraparib vs rucaparib (95% CI, 0.79-1.40; 

Adjusted HR for time to dose reduction with niraparib vs olaparib was 1.78 (95% CI, 1.43-2.22; 

 < .001), compared with 1.31 with rucaparib vs olaparib (95% CI, 0.97-1.75; 

 = .0744) and 1.37 with niraparib vs rucaparib (95% CI, 1.03-1.81; 

 = .0317). For treatment discontinuation, the adjusted HR was 1.73 with niraparib compared with olaparib (95% CI, 1.47-2.02; 

 < .001), 1.35 with rucaparib vs olaparib (95% CI, 1.09-1.66; 

 = .0056), and 1.28 with niraparib vs rucaparib (95% CI, 1.05-1.57; 

“Tolerability, or how well patients cope with the [adverse] effects of treatment, is a key consideration when selecting a PARP [inhibitor],” David O’Malley, MD, professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC – James, and coinvestigators, wrote in a poster of the data. “Here we expand on earlier work to further explore real-world tolerability and dose changes in patients with ovarian cancer receiving PARP therapy in the [US]; we also investigate how many patients continue PARP [inhibitor] therapy without treatment gaps.”

1. O’Malley D, Arend RC, Alam N. Real-world use, tolerability, and dose modifications of PARP inhibitors in ovarian cancer. 

 2022;40(suppl 16):5552. doi:10.1200/JCO.2022.40.16_suppl.5552

Patients With HR+/HER2- Advanced Breast Cancer May Reduce Ribociclib Dose Without Jeopardizing Outcomes

Dose modifications of ribociclib (Kisqali) did not demonstrate a negative effect on overall survival (OS) outcomes in postmenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer who received the therapy in combination with letrozole, according to a final protocol-specified OS analysis of the phase 3 MONALEESA-2 trial (NCT01958021).

Results were presented in a poster by Lowell Hart, MD, FACP, scientific director of clinical research at Florida Cancer Specialists and Research Institute during the 

A landmark analysis showed that the median OS among those who had at least 1 reduction 3 months into treatment was 63.1 months compared with 65.7 months among those with 0 reductions during that time frame (HR, 0.96; 95% CI, 0.68-1.36). Moreover, in a time-varying Cox regression analysis of OS by dose reduction, the median OS was 66.0 months (95% CI, 57.6-75.7) in the modification group and 60.6 months (95% CI, 42.5-79.2) in the standard group (HR, 0.87; 95% CI, 0.65-1.18).

OS outcomes were consistent with prior findings from the MONALEESA-3 (NCT02422615) and MONALEESA-7 trials (NCT02278120), suggesting that deviating from the recommended dose of 600 mg daily on a 3 weeks on/1 week off cycle in combination with endocrine therapy will yield a similar OS benefit. Notably, investigators determined that neither length of treatment nor timing of dose reduction changed these results.

1. Hart L, Bardia A, Beck T, et al. Impact of ribociclib dose modifications on overall survival in patients with HR+/HER2– advanced breast cancer in MONALEESA-2. 

. 2022;40 (suppl 16):1017. doi:10.1200/JCO.2022.40.16_suppl.1017

Vitamin D Insufficiency Predictive of Paclitaxel-Induced Peripheral Neuropathy in Early-Stage Breast Cancer

Baseline vitamin D insufficiency may be a prognostic factor for increased risk of chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving paclitaxel to treat early-stage breast cancer, according to a retrospective validation analysis of patients enrolled in the SWOG 0221 trial (NCT00070564).

Moreover, these findings may be especially meaningful for Black patients with breast cancer, as the results demonstrated that vitamin D insufficiency is more prevalent in this patient population.

The findings, which were presented in a poster by Lidia Schapira, MD, FASCO, professor of medicine at Stanford University School of Medicine, during the 

, showed that patients with vitamin D insufficiency demonstrated a higher risk of CIPN.

Vitamin D insufficiency was defined as 20 ng/mL with higher levels signifying vitamin D sufficient status. Overall, the rate of grade 3/4 CIPN was 21% (n = 397) among patients with sufficient status compared with 14% (n = 794) among those with vitamin D insufficiency (odds ratio [OR], 1.57; 95% CI, 1.14-1.15; 

 = .005). After adjusting for covariates, the odds ratio was 1.39 (95% CI, 0.98-1.97; 

Notably, the findings also revealed that Black patients had a higher incidence of vitamin D insufficiency, which may correlate with higher incidence of CIPN. Compared with White patients enrolled in SWOG 0221, 77% of Black patients (n = 109) had vitamin D insufficiency compared with 28% of White patients (n = 997).

The rate of grade 3/4 CIPN among Black patients with vitamin D insufficiency (n = 84) was 31%. these patients were also less likely to be taking vitamin D supplements (

 =.046). In an analysis comparing the association of vitamin D insufficiency with incidence of CIPN among Black patients vs White patients the odds ratio was 2.48 (95% CI, 1.57-3.86; 

“Chemotherapy-induced peripheral neuropathy is the major treatment-limiting and debilitating toxicity of paclitaxel,” the study authors wrote in the poster. “Prior retrospective studies suggest vitamin D insufficiency is associated with higher risk and severity of paclitaxel-induced [peripheral neuropathy].”

1. Chen CS, McCann SE, Budd GT, et al. Vitamin D insufficiency as a peripheral neuropathy risk factor in White and Black patients in SWOG 0221. 

 2022;40(suppl 16):12023. doi:10.1200/JCO.2022.40.16_suppl.12023

2. Budd G, Barlow WE, Moore HCF, et al. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. 

2015;33(1):58-64. doi:10.1200/JCO.2014.56.3296

Forgetfulness A Significant Barrier to Oral Adherence in Elderly Patients With Prostate Cancer

Elderly patients with advanced prostate cancer who were prescribed enzalutamide (Xtandi) reported better adherence to oral treatment than those who were prescribed abiraterone, according to findings from a prospective trial of the Meet-URO network. However, the results, which were recently presented during the 2022 ASCO meeting, showed that forgetfulness is a potential barrier to adherence with this treatment.

Non-adherence rates were assessed by comparing the number of missed pills to the number of prescribed pills though pill counting, an overall estimate was given based on the median of individual values. The percentage of missed pills per prescribed pills was 5.2% in the abiraterone cohort compared with 4.2% in the enzalutamide cohort (

 < .001). However, patients receiving enzalutamide were more likely to cite forgetfulness as their reason for non-adherence than their peers in the other cohort; the percentage of patients who cited forgetfulness as their reason was 42% (38 patients) vs 17% (4 patients), respectively (

“Physicians tend to treat elderly and frailer [patients with] mCRPC with enzalutamide,” wrote study authors in the poster. “These [patients tend to be] more adherent to treatment, however, forgetfulness is a potential barrier.”

“Despite this, [abiraterone] conferred a longer progression-free survival [PFS] in our study population,” they wrote.

1. Rescigno P, Maruzzo M, Rebuzzi SE, et al. Adherence to oral treatments in elderly advanced prostate cancer patients, the ADHERE study: a prospective trial of the MEET-URO network.

 2022;40(suppl 16):12044. doi: 10.1200/JCO.2022.40.16_suppl.12044

Frontline Bevacizumab Prolongs PFS, OS in Ovarian Clear Cell Carcinoma

The addition of bevacizumab(Avastin) to first-line chemotherapy resulted in significant improvements in progression-free survival (PFS) and overall survival (OS) compared with platinum-based chemotherapy in patients with advanced ovarian clear cell carcinoma (OCCC), according to a retrospective analysis presented at the 2022 ASCO Annual Meeting.

OCCC is a rare histological type of epithelial ovarian cancer that is typically resistant to chemotherapy, accounting for its historically poor prognosis for patients. Most patients will have early-stage disease, but about 30% have advanced disease. Seki also noted that the frequency of OCCC is more common in Asian countries, especially in Japan.

Bevacizumab has shown an impact on treating patients with epithelial ovarian cancers and was first approved in Japan in November 2013 for the treatment of patients with ovarian cancer.

 Moreover, A prior analysis in a small group of patients with OCCC showed that treatment with bevacizumab added to first-line chemotherapy led to a significant difference in PFS.

Additionally, a study of 2 potential subtypes of OCCC by gene expression signatures suggested that patients with a mesenchymal type, where angiogenesis and the PI3K-AKT and IL-6 signaling pathways were activated, may benefit more from bevacizumab than those with more epithelial expression (HR, 0.5; 

= .1978), despite higher stages of disease.

“The addition of bevacizumab to platinum-based chemotherapy improved PFS and OS in [patients with] advanced OCCC,” said Toshiyuki Seki, MD, of the Department of Obstetrics and Gynecology, Kashiwa Hospital, The Jikei University School of Medicine, Chiba, Kashiwa, Japan. “The benefit was especially significant in stage IIIA and IIIB disease.”

1. Seki T, Tate S, Nishikimi K, et al. Bevacizumab in first-line chemotherapy to improve the survival outcome for advanced ovarian clear cell carcinoma: A multicenter, retrospective analysis. 

 2022;40(suppl 16):5502. doi:10.1200/JCO.2022.40.16_suppl.5502

2. Anti-Cancer Agent “Avastin," Obtained Approval for Additional Indication of Ovarian Cancer. News release translation. Chugai Pharmaceutical Co., Ltd. November 22, 2013. Accessed June 6, 2022. https://bit.ly/3MlkMVR

3. Tate S, Nishikimi K, Matsuoka A, et al. Bevacizumab in first-line chemotherapy improves progression-free survival for advanced ovarian clear cell carcinoma. 

 2021;13(13):3177. doi:10.3390/cancers13133177

4. Tan TZ, Ye J, Yee CV, et al. Analysis of gene expression signatures identifies prognostic and functionally distinct ovarian clear cell carcinoma subtypes. 

. 2019;50:203-210. doi:10.1016/j.ebiom.2019.11.017

Articles

We rounded up 5 stories from the 2022 ASCO Annual Meeting that are of most value to oncology nurses. 

Oncology Nursing News’ Top ASCO Picks

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.

Gynecologic Cancers