Nurse navigators may play a key role in mitigating toxicities from chemotherapy and perform geriatric assessments for patients treated at hematology/oncology clinics, according to data from a pilot project presented at the 2022 ASCO Annual Meeting.

Investigators assessed the use of the G8 questionnaire to identify vulnerable geriatric patients with cancer and the Cancer and Aging Research Group (CARG) scoring tool to calculate chemotherapy toxicity risk among patients aged 65 years or older. These tools are used to stratify those at-risk for severe adverse effects using information beyond age as a guide for treatment decisions and improve outcomes. The tools also aid in the referral of patients with vulnerabilities to external services for follow-up treatment.

Completion rate of these assessments is between 20% and 35% when administered by physicians and investigators sought to improve completion rates with assistance of nurse navigators.

Seven community cancer centers were included in the pilot program and the study period lasted from May 1, 2021, to December 31, 2021, G8 assessment was administered at all 7 sites and CARG plus G8 assessments were administered among patients with solid tumors receiving chemotherapy at 4 of the 7 sites.

In total, 1372 patients were eligible to undergo G8 assessment and 563 were eligible for CARG assessment. The completion rates of the assessments were 78.9% and 91.6%, respectively, when administered by a nurse navigator.

“Nurse navigators can successfully implement G8 and CARG toxicity tool in hematology-oncology clinics in a broad range of cancer types at a high rate with resultant referrals to multiple supportive services in real-world settings,” the study authors wrote in a poster of the data.

Referrals to external services were also initiated among the population and included 193 referrals for nutrition services, 30 for audiology, 18 for physical therapy, 5 for psychiatry, and 5 for neurology. The median age of patients in the eligible population was 74 years (range, 65-100) with a near even split between men (48%) and women (52%). Patients has a range of cancers including genitourinary (18%), breast (17%), upper gastrointestinal (15%), and thoracic cancers (13%).

The G8 assessment produces a score ranging from 0 to 17 based on fitness characteristics of patients.

Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties?

Mobility (ie, able to get out of bed/chair)

Neuropsychological problems (ie, severe dementia or depression)

Heath assessed in comparison with other individuals the patient’s age

The CARG tool is used to predict cardiac toxicity based on a range of factors including the following

Primary tumor site (ie, genitourinary or gastrointestinal cancer)

Laboratory results (ie, hemoglobin and creatinine clearance)

Socialization (ie, observed decreases because of physical and emotional health)

ASCO guidelines for geriatric oncology recommend that patients aged 65 years and older should undergo assessment to identify risks that not routinely captured in clinical assessments. The recommendations include both the G8 and CARG tools as supplemental assessments for geriatric assessment in the clinic.

Shaia JL, Liu R, Sun H, et al. Nurse navigator–initiated geriatric assessments in hematology/oncology clinics. 

. 2022;40(suppl 16):12051. doi:10.1200/JCO.2022.40.16_suppl.12051

Bellera CA, Rainfray M, Mathoulin-Pélisser S, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. 

. 2021;23(8): 2166-2172. doi:10.1093/annonc/mdr587

Kim J, Hurria A. Determining chemotherapy tolerance in older patients with cancer. 

. 2013;11(12):1494-502. doi:10.6004/jnccn.2013.0176

Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. 

Articles

Nurse navigators may play a key role in mitigating toxicities from chemotherapy and perform geriatric assessments for patients treated at hematology/oncology clinics.

Geriatric Assessment Rates Improve With Nurse Navigator Intervention

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.

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

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

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

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

G12C–mutated non–small cell lung cancer (NSCLC) experienced promising intracranial activity following treatment with adagrasib (MRTX849), according to preliminary findings from the phase 1/2 trial KRYSTAL-1 trial (NCT03785249). The results, which were presented during the 2022 ASCO Annual Meeting, indicated that the agent may effectively penetrate the central nervous system (CNS). 

In patients enrolled in the phase 1b portion of KRYSTAL-1 who received adagrasib, the intracranial objective response rate (ORR) was 32%, and the median overall survival (OS) and intracranial duration of response (DOR) were not reached.

G12C–mutant NSCLC are common and are associated with a poor prognosis. Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with 

G12C–mutant NSCLC and active untreated CNS metastases,” Joshua K. Sabari, MD, from Perlmutter Cancer Center, New York University Langone Health, said in his presentation.

For patients with this type of mutated NSCLC, about 27% to 42% will have CNS metastases at diagnosis, with a 5-month median OS for patients with active and untreated CNS involvement. Targeted therapies that penetrate the CNS improve outcomes for patients with these types of complications. Adagrasib has previously shown clinical activity in treated, stable CNS metastases, and tumor regression in animal models.

Patients with advanced solid tumors and a 

G12C mutation were given adagrasib as monotherapy or combined with pembrolizumab (Keytruda), cetuximab (Erbitux), or afatinib (Gilotrif) on KRYSTAL-1, a phase 1/2 multiple expansion cohort trial. The data that were presented look at the phase 1b cohort of patients with NSCLC and active, untreated CNS metastases treated with 600 mg of oral adagrasib twice daily. Safety and clinical activity were evaluated for this portion of the trial, including systemic and intracranial ORR by blinded independent central review (BICR), OS, DOR, and progression-free survival (PFS).

There were 25 patients enrolled, although not all were evaluable for efficacy of adagrasib. The median age in this cohort was 66 years (range, 47-89), and 52% of patients were female. A majority of patients were white (84%), had ECOG performance status of 1 (72%), and were current or former smokers (96%). About half of patients had received 1 prior line of therapy (20%), and the rest had received 0 (12%), 2 (20%), or 3 or more (16%) lines of therapy. Target CNS lesions at baseline were observed in 19 patients of the 25 patients and non-target lesions in 18 of the patients.

Among the overall evaluable population (n = 19), the ORR was 32%; for patients with only non-target lesions (n = 4) and target lesions with or without non-target lesions (n = 15), it was 50% and 27%, respectively. The complete response rate was 16% in the overall group, 50% in the non-target lesion group, and 7% in the target lesion group. Partial responses were also seen in 16% overall and 20% in patients with target lesions, but not in any patients with only non-target lesions.

Fifty-three percent of patients in both the overall and target lesion groups had stable disease (SD), while 50% had SD in the non-target lesion group. Investigators observed progressive disease in 11% of patients overall, 13% with target lesions, and none with non-target lesions. The disease control rate (DCR) was 84%, 80%, and 100%, for patients in the overall, target lesion, and non-target lesion groups.

“[In] the waterfall plot for BICR, intracranial disease control was broad, with intracranial tumor shrinkage of any magnitude occurring in 80% of radiographically evaluable patients with target lesions. One additional patient demonstrated 100% regression in the target lesions, however, [the patient] was non-evaluable due to the scans being performed too early,” Sabari noted.

There were objective intracranial responses observed in 32% of all patients (95% CI, 12.6%-56.6%). The intracranial DCR was 84% (95% CI, 60.4%-96.6%). Fourteen of the 16 patients who responded had concordance between systemic and intracranial disease control. Additionally, the systemic ORR by RECIST v1.1 was 37% (95% CI, 16.3%-61.6%) and the systemic DCR was 79% (95% CI, 54.4%-93.9%).

At median follow-up of 6.6 months, the median OS had not been reached. The median intracranial PFS was 4.2 months (95% CI, 3.8-not estimable [NE]). The median intracranial DOR had also not been reached (95% CI, 4.1-NE). Of the responders, 83% were still on therapy at the data cutoff of December 31, 2021.

An average Kp, uu of 0.47 was seen in 2 patients who had cerebrospinal fluid collected, which exceeds the values for patients who have received tyrosine kinase inhibitors that have shown CNS penetration and antitumor activity in CNS metastases. “Of note, both patients had evidence of CNS regression in their lesions via imaging compared to baseline. [One patient also] demonstrated a decrease in the edema compared to baseline,” Sabari said.

According to the safety profile, grade 1 or 2 treatment-related adverse events (TRAEs) occurred in 60% of the 25 patients who were evaluable for toxicity. There were no grade 4 or 5 TRAEs observed with adagrasib monotherapy. The most frequent grade 3 TRAEs were vomiting in 12%, and diarrhea, alanine transferase, and dizziness in 8% of patients each. Dose reductions/interruptions due to TRAEs were needed for 48% of patients, and discontinuation was needed in 1 patient (4%). CNS-specific TRAEs occurred in 6 patients, 5 reporting dizziness and 1 reporting grade 1/2 aphasia and insomnia.

 G12C inhibitor to demonstrate clinical activity in patients with 

G12C-mutated NSCLC with both treated as well as active, untreated CNS metastases,” Sabari stated. “An expanded-access program is open and enrolling patients with 

G12C-mutant solid tumors, including patients with active and untreated CNS metastases.”

Sabari JK, Spira AI, Heist RS, et al. Activity of adagrasib (MRTX849) in patients with KRASG12C-mutated NSCLC and active, untreated CNS metastases in the KRYSTAL-1 trial. 

. 2022;40(suppl 17):LBA9009. doi:10.1200/JCO.2022.40.17_suppl.LBA9009

The intracranial objective response rate was 32% among patients with KRAS G12C–mutant, non–small cell lung cancer who received adagrasib.

Adagrasib Demonstrates CNS Activity in KRAS G12C+ NSCLC

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

Findings from a subgroup analysis of the phase 2 MAIA trial (NCT02252172) demonstrated that daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) yielded superior responses over Rd alone in transplant-ineligible patients with newly diagnosed multiple myeloma–regardless of renal function or cytogenetic risk.

The findings, which were presented at the 

Daratumumab plus lenalidomide and dexamethasone bested standard therapy in producing rapid, deep, and durable responses across subgroups of patients with newly diagnosed multiple myeloma. 

ASCO Annual Meeting