Niraparib/Abiraterone Combo Is Linked With Improved rPFS in Select Patients With mCRPC

Patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations who received frontline treatment with niraparib (Zejula), abiraterone acetate (Zytiga), and prednisone 

experienced superior radiographic progression-free survival

 (rPFS) compared with those who received placebo plus abiraterone/prednisone, according to findings from the phase 3 MAGNITUDE trial (NCT03748641). These findings were presented during the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium.

In the BRCA1/2 population, the median rPFS was 16.6 months with niraparib/ abiraterone vs 10.9 months with placebo/ abiraterone (HR, 0.53; 95% CI, 0.36-
0.79; P = .0014) at a median follow-up of 18.6 months. The investigator-assessed rPFS was 19.3 months with niraparib/ abiraterone and 12.4 months with placebo/ abiraterone (HR, 0.50; 95% CI, 0.33-0.75; P = .0006).


Among all patients with HRR gene alterations, the median rPFS was 16.5 months vs 13.7 months, respectively (HR, 0.73; 95% CI, 0.56-0.96; P = .0217). Here, the investigator-assessed rPFS was 19.0 months and 13.9 months, respectively (HR, 0.64; 95% CI, 0.49-0.86; nominal P = .0022).

As many as 30% of patients with mCRPC will harbor alterations in genes associ- ated with HRR. Although these alter- ations reflect poor prognosis, they have also shown increased sensitivity to PARP inhibitors, such as niraparib. Notably, the addition of an antiandrogen agent like abiraterone has been theorized to augment responses in all-comers, serving as the rationale for the randomized, double-blind MAGNITUDE trial, which evaluated the value of adding niraparib to abiraterone in patients with mCRPC with and without HRR gene alterations.

“The MAGNITUDE study results support niraparib plus abiraterone as a new first- line treatment option for patients with mCRPC and alterations in genes associ- ated with HRR,” lead study author Kim N. Chi, MD, senior research scientist at the Vancouver Prostate Centre, chief medical officer and vice president for BC Cancer, medical oncologist at BC Cancer–Vancouver, and professor in the Department of Medicine at The University of British Columbia in Canada, said in a presentation of the data.

Chi KN, Rathkopf DE, Smith MR, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2022;40(suppl 6):12. doi:10.1200/JCO.2022.40.6_suppl.012

Frontline Nivolumab Plus Cabozantinib Is Linked With Superior Quality of Life in Advanced RCC


Patients with advanced renal cell carcinoma who received the frontline combination of nivolumab (Opdivo) plus cabozantinib (Cabometyx) maintained superior health-related quality of life (HRQOL) compared with those on sunitinib (Sutent), according to

onger follow-up of the CheckMate 9ER trial

 (NCT03141177). The maintained effects, which were presented during the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium, were seen across multiple defi- nitions of deterioration, suggesting that the benefit with the combination is sustainable in the long term.

In a 32.9-month follow-up, patient- reported outcomes (PRO) scores revealed that patients receiving nivolumab/ cabozantinib had maintained or improved HRQOL compared with patients in the sunitinib arm. The longitudinal changes from baseline consequently showed statis- tical significance (P < .05) in favor of the experimental regimen for all scores except FKSI-19 functional well-being.

In the 151 weeks following baseline, patients receiving nivolumab/cabozantinib experienced a –0.47 least square (LS) mean change from baseline FKSI-19 total score compared with a –2.84 decline with those in the sunitinib arm (overall difference in mean change, 2.37; P < .0001). For the FKSI-19 disease-related symptoms score, patients receiving nivolumab/cabozantinib experienced an LS mean change from base- line of 0.71 compared with –0.46 in the sunitinib arm (1.17; P < .0001).

Similarly, patients receiving nivolumab/ cabozantinib experienced an EQ-5D-3L health status score of 2.73 compared with –0.95 in the sunitinib group (3.68; P = .0001). The EQ-5D-3L UK utility index score demonstrated that patients receiving nivolumab/cabozantinib experienced an LS mean change from baseline of –0.01 compared with –0.06 in the sunitinib arm (0.05; P = .001).

At baseline, both arms demonstrated a high PRO completion rate of at least 90%. By week 151, the rates were over 75% and 73% in the nivolumab/cabozantinib and sunitinib arms, respectively. At baseline, both arms demonstrated relatively low symptom burden.

“At nearly 3 years of follow-up, patients continued to report improved HRQOL with nivolumab/cabozantinib compared with sunitinib,” lead study author and coinvestigator David Cella, FASCO, PhD, chair of the Department of Medical Social Sciences and director of the Institute for Public Health and Medicine at Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois, wrote in a poster presentation of the findings. “Treatment with [nivolumab/ cabozantinib] was observed to reduce the risk of clinically meaningful deterioration in HRQOL scores in comparison with suni- tinib, regardless of definition of deterioration.”

Cella D, Motzer RJ, Blum SI, et al. Health-related quality of life (HRQoL) in previously untreated patients with advanced renal cell carcinoma (aRCC): CheckMate 9ER updated results. J Clin Oncol. 2022;40(suppl 6):323. doi:10.1200/ JCO.2022.40.6_suppl.323

Darolutamide Prolongs OS in Patients With Nonmetastatic CRPC Plus Comorbidities and Concomitant Medications

Darolutamide (Nubeqa), an androgen receptor inhibitor,

yielded positive responses in patients with nonmetastatic castration-resistant prostate cancer

(CRPC), who were also being treated with concomitant medications or had comorbidities, according to phase 3 data presented at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Patients with nonmetastatic CRPC from the ARAMIS trial (NCT02200614) were randomized 2:1 to receive either darolutamide (n = 955) or placebo (n = 554) while continuing treat- ment with androgen deprivation therapy.

At the final data cutoff date of November 15, 2019, overall survival (OS) and adverse events were evaluated in patients with a median of 6 or fewer or more than 6 comorbidities and 10 or fewer or more than 10 concomitant medications. Comorbidities evaluated included metabolic, cardio- vascular (CV), and other (osteoarthritis, arthralgia, back pain, benign prostatic hyperplasia, constipation, gastroesoph- ageal reflux, and renal insufficiency).

Concomitant medication classes/subclasses included gastrointestinal/metabolic, CV (antihypertensives and nonantihyperten- sives), pain/inflammation, and urologic.

“[Over] 50% of the patients in the ARAMIS trial, which was a very significant number of patients...had a minimum of 6 or more comorbidities of significance,” study coauthor Neal Shore, MD, FACS, US Chief Medical Officer of Surgery and Oncology at GenesisCare USA, and director of the Carolina Urologic Research Center, said in a presentation during the meeting. Specifically, 795 of the total cohort of 1509 patients had at least 6 comorbidities, and 813 patients had received at least 10 concomitant medications.

The investigators reported that, in patients with at least 6 and more than
6 comorbidities, darolutamide prolonged OS compared with placebo (HR, 0.65 and 0.73, respectively). The OS benefit for darolutamide was found to be consistent in patients with metabolic, CV, and other comorbid disorders (HR range, 0.39-0.88). OS was also prolonged in patients receiving at least 10 and more than 10 concomitant medications (HR, 0.76 and 0.66, respectively).

“Subgroups of [patients] receiving concomitant medications for gastrointes- tinal/metabolic disorders, CV disease, urologic disorders, and pain/inflammation achieved similar OS benefit with [darolut- amide vs placebo] with an [HR range of 0.45–0.80],” the authors wrote.

“What we’re showing here is that the OS benefit [and] the safety analysis [were rather significant], regardless of the number of comorbidities,” Shore said.

Fizazi K, Shore ND, Smith MR, et al. Efficacy and safety outcomes of darolutamide in patients with nonmeta- static castration-resistant prostate cancer with comor- bidities and concomitant medications from ARAMIS. J Clin Oncol. 2022;40(suppl 6):256. doi:10.1200/ JCO.2022.40.6_suppl.256


Neoadjuvant Enfortumab Vedotin Shows Potential in Cisplatin-Ineligible Muscle- Invasive Bladder Cancer


Patients with muscle-invasive bladder cancer (MIBC) who were not eligible for cisplatin 

experienced promising antitumor responses after receiving neoadjuvant enfortumab vedotin

(Padcev), according to preliminary findings from cohort H of the phase 1b/2 EV-103 trial (NCT03288545). These findings were presented during the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Investigators reported a pathological complete response rate of 36.4% (95% CI, 17.2%-59.3%) among those treated with enfortumab vedotin (n = 22) and a pathological downstaging rate of 50.0% (95% CI, 28.2%-71.8%).

“This first disclosure of data support the ongoing phase 2 and 3 programs evaluating enfortumab vedotin alone or in combi- nation with pembrolizumab (Keytruda) in MIBC,” lead study author Daniel P. Petrylak, MD, professor of medical oncology and urology at the Yale Cancer Center in New Haven, Connecticut, said in a presentation of the data.

Patients received 1.25 mg/kg of neoad- juvant enfortumab vedotin monotherapy on days 1 and 8 per 21-day cycle for 3 cycles. Within 4 weeks of treatment, patients underwent radical cystectomy plus pelvic lymph node dissection, followed by imaging every 12 weeks for the first 2 years, then every 24 weeks after.

The most common reason for cisplatin ineligibility was creatinine clearance between less than 60 and 30 or more mL per minute (50.0%), followed by grade 2 or greater hearing loss (40.9%). A total of 86% of patients completed all 3 cycles of neoadjuvant therapy.

Any-grade enfortumab vedotin–related treatment-emergent adverse events (TEAEs) were seen in all patients. Common TEAEs included fatigue (45.5%), alopecia (36.4%), dysgeusia (36.4%), diarrhea (27.3%), nausea (27.3%), peripheral sensory neuropathy (27.3%), dry eye (22.7%), and maculopap- ular rash (22.7%). Four patients experienced grade 3 or higher TEAEs, and no grade 4 TEAEs or deaths were reported. Grade 3 TEAEs related to treatment with enfortumab vedotin included asthenia, dehydration, erythema multiforme, and hyperglycemia.

In the safety analysis, 3 enfortumab vedotin–related TEAEs leading to dose interruptions, 2 TEAEs leading to dose reductions, and 3 TEAEs leading to discon- tinuations were observed. Most adverse events (AEs) of special interest were grade 1 and 2. Any-grade AEs of interest included peripheral neuropathy (36.4%), skin reac- tion (63.6%), hyperglycemia (22.7%), ocular disorder (40.9%), and infusion-re- lated reactions (9.1%). Grade 3 or greater AEs of special interest were skin reactions (9.1%) and hyperglycemia (13.6%).

“The observed safety profile of neoad- juvant enfortumab vedotin monotherapy in patients with cisplatin-ineligible MIBC is consistent with the known AE profile of enfortumab vedotin in other settings,” Petrylak said.

Petrylak DP, Flaig TW, Mar N, et al. Study EV-103 cohort H: antitumor activity of neoadjuvant treatment with enfor- tumab vedotin monotherapy in patients (pts) with muscle invasive bladder cancer (MIBC) who are cisplatin-inel- igible. J Clin Oncol. 2022;40(suppl 6):435. doi:10.1200/ JCO.2022.40.6_suppl.435

Articles

PARP inhibitors emerge as frontline treatment in metastatic castration-resistant prostate cancer, immunotherapy combinations improve quality of
life in advanced renal cell carcinoma, and antibody drug conjugates show promise in cisplatin-ineligible urothelial cancer.

Nurse Takeaways: 2022 ASCO Genitourinary Cancers Symposium at a Glance

Trastuzumab Deruxtecan Improves OS in Select Gastric/GEJ Cancer


Updated trial survival results from the phase 2 DESTINY-Gastric01 trial (NCT03329690) revealed that fam-trastuzumab deruxtecan-nxki (Enhertu) 

reduced mortality rates by 40% compared with standard chemotherapy

among patients with HER2-positive gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma. The data were presented during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The updated median overall survival (OS) with trastuzumab deruxtecan remained at 12.5 months (95% CI, 10.3-15.2) compared with 8.9 months (95% CI, 6.4-10.4) with chemotherapy (HR, 0.60; 95% CI, 0.42-0.86).

In January 2021, the FDA approved trastu- zumab deruxtecan for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarci- noma who have received a previous trastu- zumab (Herceptin)-based regimen.

“With continued follow-up after the primary analysis, trastuzumab deruxtecan demonstrated a clinically meaningful OS benefit and clinically relevant improve- ment in [objective response rate] compared with standard chemotherapy in HER2- positive advanced gastric or GEJ cancer,” lead study author Kensei Yamaguchi, MD, of The Cancer Institute Hospital of the Japanese Foundation for Cancer Research in Tokyo, Japan, said in a presentation during the meeting.

Yamaguchi K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2–positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01). 

. 2022;40(suppl 4):242. doi:10.1200/JCO.2022.40.4_suppl.242

FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. News release. FDA; January 15, 2021. Accessed January 15, 2021. http://bit.ly/35KBZ8T

Ivosidenib Maintains Quality of Life in Patients With Cholangiocarcinoma 

promising preservation of health-related quality of life 

among patients with advanced chemotherapy-refractory cholangiocarci- noma and an IDH1 mutation, according to a long-term follow-up of the ClarIDHy study (NCT02989857). The data were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Investigators specifically assessed how the oral targeted therapy impacted patients’ physical function, pain, and appetite loss compared with placebo. In terms of phys- ical function, the changes between baseline and 27 days of treatment did not reach the prespecified 12- to 13-point threshold— marking a lack of clinically meaningful decline among those treated with ivosidenib.

However, patients who received placebo demonstrated clinically meaningful dete- rioration across multiple cycles. Similarly, for pain, appetite loss, and eating, the least square means of change were reported for patients receiving ivosidenib compared with those on placebo.

“Cholangiocarcinoma is a rare and aggressive cancer, and treatment options
are primarily limited to chemotherapy. Mutations in the IDH1 protein have been found to occur in approximately 1% to 3% of intrahepatic cholangiocarcinomas and 1% of extrahepatic cholangiocarcinomas globally,” Christina X. Chamberlain, PhD, of Servier, explained in a presentation of the findings.

“Overall, patients who remain on ivosid- enib tend to maintain their health-related quality of life based on the least squares mean changes over time from baseline through cycle 27, day 1, which corresponds approximately to year 2,” she said.

Chamberlain CX, Hua Z, Gliser C, et al. Longitudinal trends in health-related quality of life (HRQoL) among patients treated with ivosidenib (IVO) for 

-mutated cholangiocarcinoma (CCA) in the ClarIDHy study. 

. 2022;40(suppl 4):388. doi:10.1200/JCO.2022.40.4_suppl.388

Adding Nivolumab to Encorafenib/ Cetuximab Yields High Response Rates in MSS, BRAF V600E+ Metastatic CRC 

Patients with refractory microsatellite stable, BRAF V600E–mutant metastatic colorectal cancer 

experienced high response rates and manageable adverse events 

after receiving nivolumab (Opdivo) in addition to encorafenib (Braftovi) plus cetuximab (Erbitux), according to data from a phase 1/2
trial (NCT04017650), presented during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The results highlighted an overall response rate of 50% (95% CI, 28%-72%) among those treated with the combina- tion, with all patients achieving partial responses. The disease control rate was 96% (95% CI, 77%-100%).

“Encorafenib, cetuximab, and nivolumab appears to be a safe and well-tolerated combination,” lead study author Van K. Morris, MD, an assistant professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, said during a presentation of the data. “The efficacy of this combination appears promising when considering the precedent of encorafenib and cetuximab alone from the previ- ously reported BEACON [CRC] study [NCT02928224].”

The study regimen included a 300-mg dose of oral encorafenib that was administered daily, 500 mg/m2 of cetuximab intravenously every 14 days, and 480 mg of nivolumab intravenously every 28 days.

Morris VK, Parseghian CM, Escano M, et al. Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAF V600E metastatic colorectal cancer. 

. 2022;40(suppl 4):12. doi:10.1200/JCO.2022.40.4_suppl.012

Ivosidenib maintains quality of life in cholangiocarcinoma, immunotherapy outperforms chemotherapy in select gastric/gastroesophageal junction adenocarcinoma, and nivolumab induces high response rates are observed among patients with BRAF V600E–mutant metastatic colorectal cancer.

2022 ASCO Gastrointestinal Cancers Symposium Highlights

Oncology Nursing News® regrets to inform our readers that our beloved chairman and founder of MJH Life Sciences®, Michael J. Hennessy Sr, has passed away. Hennessy was a fierce supporter of oncology nurses and was devoted to improving the lives of patients with cancer. 

Hennessy spent his career turning his passion for building businesses and creating jobs into a run of successful ventures and brands. Following his graduation from Rider University in 1982, he started his career in medical publishing as a sales trainee, eventually advancing to the position of chief operating officer. In 1986, Hennessy became chief operating officer of Medical World Business Press, which was part of the launch of medical newspapers and other media products. The company prospered and was eventually sold to a Boston-based venture capital firm.

Hennessy launched Multimedia Healthcare Communications, LLC, in 1993 and built a portfolio of award-winning clinical journals. In 2001, Freedom Communications, Inc, acquired Multimedia Healthcare, about the time that Hennessy was pioneering a new approach to print and digital publishing with Intellisphere®, LLC (now part of MJH Life Sciences®). Guided by the principles of innovation and entrepreneurial spirit and reflecting its founder’s dedication to improving quality of life through health care research and education, Intellisphere® publishes a variety of integrated print and digital products focusing on a range of topics in research and clinical medicine. 

Hennessy’s commitment to improving the lives of patients with cancer is deeply rooted within the halls of MJH Life Sciences®. As a complement to the industry-leading OncLive® platform, he developed the Giants of Cancer Care® awards to recognize the leaders and pioneers who often go unrecognized for their contributions to advancing oncology care. He further strengthened his commitment to education by acquiring CURE Media Group in 2014, followed by the purchase of the Chemotherapy Foundation Symposium, in his quest to provide oncology professionals with focused education on innovative cancer therapy.

Later, in 2019, Hennessy elevated his role to chairman while naming his son Mike Hennessy Jr to assume the leadership role of the organization and carry on the family legacy. Under Mike Jr’s leadership, the company enhanced its global potential by entering into a long-term partnership with BDT Capital Partners, LLC, in November 2021.

Because of his broad business and educational experience and understanding of the challenges facing New Jersey, Hennessy’s counsel and insight had been sought out by several organizations including Rider University, where he served on the Board of Trustees and was elected to the executive committee. In addition to being active in state and national politics, Hennessy also had a long record of service at the local level, where he was a strong advocate for veterans and environmental issues.

Hennessy’s true passion was his relationship with his wife, Patrice “Patti” Hennessy. After meeting her in college, Hennessy devoted his life to Patti and his family, raising 4 wonderful children, Shannon, Ashley, Mike Jr, and Chris. Hennessy was Patti’s rock as she bravely battled cancer for almost 10 years until her death in January 2020. Hennessy recently honored Patti by making a donation to Rider University to expand the Science and Technology Center at their alma mater. The Mike and Patti Hennessy Science and Technology Center is set to be completed in 2022.

Hennessy’s legacy and “family first” mantra will live on through his children; their spouses Matt, Phil, Rachel, and Jordan, and his 10 grandchildren. He will be greatly missed by his family, friends, and MJH Life Sciences® family.

Hennessy spent his career turning his passion for building businesses and creating jobs into a run of successful ventures and brands.

Remembering Michael J. Hennessy Sr

Immunotherapy May Represent New Standard of Care in Metastatic TNBC 

Pembrolizumab (Keytruda) plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) vs chemotherapy alone in patients with previously untreated, locally recurrent, inoperable, or metastatic triple-negative breast cancer (TNBC) with a PD-L1 combined positive score (CPS) of 10 or higher, 

according to updated data from the phase 3 KEYNOTE-355 trial 

Furthermore, a PD-L1 CPS of at least 10 was found to be a reasonable cutoff to define the population of patients expected to derive the most benefit from this regimen. Results showed that the combination of pembrolizumab and chemotherapy yielded a median OS of 23.0 months vs 16.1 months with chemotherapy alone in patients with a CPS of 10 or higher (HR, 0.73; 95% CI, 0.55- 0.95; P = .0093). The 18-month OS rates were 58.3% with pembrolizumab vs 44.7% with placebo or chemotherapy. 

Moreover, the median PFS elicited by the combination was 9.7 months vs 5.6 months in patients with a CPS of at least 10 (HR, 0.66; 95% CI, 0.50-0.88). The 12-month PFS rate was 39.1% with pembrolizumab and 23.0% with placebo or chemotherapy. 

“These results provide further support for pembrolizumab in combination with chemotherapy as the new standard-of-care treatment regimen for patients with locally recurrent, unresectable, or metastatic TNBC whose tumors express a PD-L1 CPS of 10 or more,” said lead study author Javier Cortés, MD, PhD, head of breast cancer and gynecological cancers at Hospital Universitario Ramón y Cajal in Madrid, Spain, in a presentation of the data.

Cortes J, Cescon DW, Rugo HS, et al. Final results of KEYNOTE-355: randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.

Do Oral SERDs Hold Potential to Change Outpatient Practices?

The selective estrogen receptor degrader (SERD) elacestrant (RAD1901) led to a 30% reduction in the risk of disease progression or death compared with standard of care (SOC) in patients with estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer who previously received CDK4/6 inhibition, 

according to results from the EMERALD trial

Data from the phase 3 trial showed that the median progression-free survival (PFS) by independent review was 2.79 and 1.91 months with elacestrant and standard therapy, respectively, in the intentto-treat population (HR, 0.697; 95% CI, 0.552-0.880; P = .0018). Standard therapy included either fulvestrant (Faslodex) or an aromatase inhibitor. 

In a subgroup of patients with ESR1 mutations, elacestrant was linked with a median PFS of 3.78 months vs 1.87 months with standard therapy. This led to a 45% reduction in the risk of disease progression or death in this subgroup (HR, 0.546; 95% CI, 0.387-0.768; P = .0005). 

Elacestrant, an oral SERD that blocks ER in a dose-dependent manner, has previously shown clinical activity in postmenopausal women with ER-positive, HER2-negative metastatic breast cancer.

Notably, experts have expressed that continued positive trial outcomes with oral SERDs have the potential to change outpatient practice by eliminating the need for intramuscular fulvestrant injections.

“Because it is an oral agent, the [main] thing to consider is that it does cause nausea,” stated Aditya Bardia, MD, MPH, Dana-Farber Harvard Cancer Center, 

in an interview with Oncology Nursing News®

 “It can also cause upper GI [gastrointestinal] discomfort. So, those are important education pieces for patients. If a patient is having a lot of acidlike symptoms, then the use of a proton pump inhibitor or other anti-acid [antacid] medications would be very reasonable. If a patient really has severe nausea, then the use of antinausea medication would be reasonable. But overall, the drug is well tolerated.”

Bardia A. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: results of EMERALD phase 3 trial. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.

Bihani T, Patel HK, Arit H, et al. Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), has antitumor activity in multiple ER+ breast cancer patient–derived xenograft models. 

. 2017;23(16):4793-4804. doi:10.1158/1078-0432.CCR-16-2561

Bardia A, Kaklamani V, Wilks S, et al. Phase I study of elacestrant (RAD1901), a novel selective estrogen receptor degrader, in ER-positive, HER2-negative advanced breast cancer. 

 2021;39(12):1360-1370. doi:10.1200/JCO.20.02272

Dr Tolaney on the safety profile of SAR439859 in ER+/HER2 metastatic breast cancer. OncLive®. December 10, 2020. Accessed December 22, 2021. 

https://www.onclive.com/view/dr-tolaney-on-the-safety-profile-of-sar439859-in-er-her2--metastatic-breast-cancer

Breast Cancer–Related Lymphedema Rate Is Higher in Black Women Than White Women

Data presented at the 2021 San Antonio Breast Cancer symposium revealed that in patients with breast cancer

 treated with axillary lymph node dissection (ALND) and radiotherapy there is a 3.5-fold increased incidence of lymphedema among Black women compared with non-Black women.

The results also indicated that Hispanic women have a 3-fold increased incidence of breast cancer–related lymphedema compared with White women. However, Andrea V. Barrio, MD, FACS, an associate attending physician in the Breast Service, Department of Surgery at Memorial Sloan Kettering Cancer Center in New York, New York, remarked that more data are needed to confirm this observation. 

“Notably, the number of Hispanic women in our study was small,” explained Barrio, lead study author, in a presentation of the data during a press briefing ahead of the conference. 

At the beginning of her presentation, Barrio noted that results from epidemiological studies have shown that Black women with breast cancer have an increased susceptibility to developing lymphedema. However, as she discussed, there are very few prospective clinical trial data confirming those results. 

“The aim of our study was to assess the incidence of lymphedema in a prospective cohort of patients treated with ALND to identify risk factors associated with lymphedema development and to evaluate the impact of race and ethnicity on lymphedema incidence and severity,” she said. 

To evaluate this incidence, Barrio and her colleagues enrolled 827 women age 18 years and older with breast cancer in the trial. Patients also had to have received a unilateral ALND either in the primary setting or after a sentinel lymph node biopsy to be eligible for inclusion in the analysis. 

At a median follow-up of 22.6 months, 56 patients had developed lymphedema. The results demonstrated that the 12-month lymphedema rate was 8.8% (95% CI, 5.9%- 13%) and that the 24-month rate was 24.7% (95% CI, 19.2%-31.5%). The highest incidence of lymphedema observed was among Black women, with a 24-month lymphedema rate of 39.4%. That rate was 27.7% in Hispanic women, 23.4% in Asian women, and 20.5% in White women. 

The results also showed that receipt of neoadjuvant chemotherapy was associated with a higher 24-month lymphedema rate compared with up-front surgery at 30.9% vs 11.1% (P = .0066). Of note, among women with lymphedema, disease severity did not vary across racial and ethnic groups with similar relative volume changes observed. 

“We observed a higher incidence of lymphedema in Black women treated with ALND and radiotherapy after adjustment for other variables. Similar findings were observed in Hispanic women, but confirmation in a larger data set is needed,” Barrio concluded.

Barrio AV, et al. Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: results of a prospective screening study. Abstract presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX.

Combination therapy, selective estrogen receptor degraders, and more were covered at the 2021 San Antonio Breast Cancer Symposium.

SABCS 2021 Highlights & Conclusions

Acalabrutinib Provides Long-Term Survival Benefits vs Standard of Care in Relapsed/Refractory CLL 

Treatment with acalabrutinib (Calquence) for relapsed/refractory chronic lymphocytic leukemia was effective out to 3 years and demonstrated a progression-free survival (PFS) benefit over standard of care, 

according to a 3-year follow-up of the ASCEND study 

Long-term follow-up data from ASCEND, which were presented by Wojciech Jurczak, MD, PhD, head of the Department of Hematology at Maria Sklodowska-Curie National Research Institute of Oncology in Kraków, Poland, also demonstrated that acalabrutinib was well tolerated with no new safety findings. 

During follow-up, patients treated with acalabrutinib monotherapy had significantly prolonged PFS compared with those treated with idelalisib (Zydelig)/rituximab (Rituxan) or bendamustine (Bendeka)/rituximab (median, not reached [NR] vs 16.8 months; HR, 0.29; 95% CI, 0.21-0.41; P < .0001). More patients in the acalabrutinib group achieved 36-month PFS compared with those in the investigator–selected treatment group (63% vs 21%). When investigators assessed the groups separately, they observed similar benefits regarding PFS when comparing acalabrutinib with idelalisib/rituximab (median, 16.2 months; HR, 0.31; P < .0001) and with bendamustine/rituximab (median, 18.6 months; HR, 0.25; P < .0001). 

“Overall, these data support the use of acalabrutinib in patients with relapsed/ refractory chronic lymphocytic leukemia, including those with high-risk features,” Jurczak said during the presentation.

Jurczak W, Pluta A, Wach M, et al. Three-year follow-up of the ASCEND trial: acalabrutinib vs rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia. Presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA.

Ibrutinib Plus FCR Shows Encouraging Activity as Time-Limited Option for Younger Patients With CLL 

The addition of ibrutinib (Imbruvica) to fludarabine, cyclophosphamide, and rituximab (Rituxan; iFCR) resulted in a higher rate of complete responses (CRs) with bone marrow undetectable minimal residual disease (BM-uMRD) in younger, fit patients with chronic lymphocytic leukemia (CLL), 

according to long-term data from a phase 2 study 

Moreover, these results included patients with unmutated IGHV, a population who rarely has durable responses, according to Matthew S. Davids, MD, MMSc, director of clinical research in the Division of Lymphoma at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School. 

“Other studies have suggested that patients treated with ibrutinib-based therapy have variable benefits, even with IGHV-unmutated disease. However, we have not seen larger data yet for the combination of ibrutinib with FCR,” said Davids during a presentation of the data. “We hypothesized that combining ibrutinib with FCR as initial therapy would lead to a high rate of CR with BM-uMRD in a broad population of younger, fit patients [with CLL].” 

The median number of ibrutinib maintenance cycles was 24 (range, 0-81). In the intent-to-treat (ITT) population, the rate of CR with BM-uMRD improved to 55% (n = 47) and the best rate of BM-uMRD remained at 84% (n = 71). The CR rate deepened with ibrutinib maintenance therapy, from 34% to 81% as the best rate. This was similar among the IGHV-mutated and -unmutated patients, up from 41% to 88% and up from 28% to 76%, respectively, as the best rates. Lastly, the BM MRD-negative rates in the ITT population were 91% in the 81 patients with the TP53 mutation. With the time-limited novel agent plus chemoimmunotherapy, 3-year progression-free and overall survival rates were 97% and 99%, respectively. Thirteen patients (21.3%) who discontinued ibrutinib have had recurrent BM-MRD, including 5 patients with clinical progression of CLL. Seven patients restarted treatment with ibrutinib, all of whom have experienced partial responses. The median time on retreatment is 12.8 months (range, 4.2-26.2).

Davids MS, Brander DM, Tyekucheva S, et al. Longer-term follow-up of a multicenter, phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, rituximab (iFCR) as initial therapy for younger patients with chronic lymphocytic leukemia. Abstract presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA.

Cilta-Cel Continues to Impress With Durable and Deep Responses in Relapsed/Refractory

Ciltacabtagene autoleucel (cilta-cel) elicited a 97.9% objective response rate (ORR) and an 82.5% stringent complete response (sCR) rate in patients with relapsed/refractory multiple myeloma at a median of approximately 2 years of follow-up, 

from the phase 1b/2 CARTITUDE-1 trial (NCT03548207).

Additionally, the 2-year progression-free and overall survival (OS) rates were 60.5% and 74.0% in all patients, respectively, and minimal residual disease (MRD) negativity was achieved in 92% of evaluable patients for MRD (n = 61). The 2-year progression-free survival (PFS) rates were improved in those who had MRD negativity sustained for at least 6 and 12 months, at 91% and 100%, respectively, as well as the 2-year OS rates at 100% and 100%. 

“These data are encouraging, and they suggest that cilta-cel will be an important treatment option for patients with multiple myeloma,” said lead study author Thomas Martin, MD, a clinical professor of medicine in the Adult Leukemia and Bone Marrow Transplantation Program, and associate director of the Myeloma Program at the University of California, San Francisco, in a presentation on the data. 

Cilta-cel is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy with 2 BCMA-targeting single-domain antibodies that are designed to confer avidity. A biologics license application seeking approval for the agent is currently under priority review with the FDA for its use in adult patients with relapsed and/or refractory multiple myeloma. 

In November 2021, the FDA extended the Prescription Drug User Fee Act target date for the application to review recently submitted data linked with an updated analytical method following the agency’s request for information request that was issued by the agency.

 The new action date is February 28, 2022.

Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2Study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T-cell therapy, in patients with relapsed/refractory multiple myeloma. Abstract presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA.

US Food and Drug Administration grants BCMA CAR-T cilta-cel priority review for the treatment for relapsed/refractory multiple myeloma. News release. Legend Biotech Corporation. May 26, 2021. Accessed December 13, 2021. 

Liso-Cel Outperforms Standard Therapy in Improving QoL in Relapsed/Refractory LBCL

Lisocabtagene maraleucel (liso-cel; Breyanzi) fostered a better quality of life (QOL) in patients with relapsed/refractory large B-cell lymphoma (LBCL) compared with current standard of care (SOC), 

according to data from a comparative analysis of the phase 3 TRANSFORM trial 

Evaluable patients who received the chimeric antigen receptor (CAR) T-cell therapy (n = 47) experienced a mean change in cognitive functioning of 2.21 (range, –1.48 to 5.90) vs –2.09 (range, –6.00 to 1.83) in those who received SOC (n = 43); this translated to a difference of 4.30 (range, –0.76 to 9.36) on day 126 from baseline. 

Those in the liso-cel arm also experienced a mean change in fatigue of –1.95 (range, –7.40 to 3.51) compared with 3.75 (range, –2.17 to 9.68) in the SOC arm, equating to a difference of –5.70 (range, –13.24 to 1.84) on day 126 from baseline. In these domains, the liso-cel group improved, whereas the SOC group deteriorated. 

The liso-cel group also experienced mean changes in physical functioning and pain of –2.75 (range, –6.76 to 1.25) and –11.14 (range, –16.37 to –5.92), respectively, compared with –2.17 (range, –6.64 to 2.30) and –15.56 (range, –21.25 to –9.88), respectively, for the SOC group. The differences between the 2 arms in physical functioning and pain were –0.58 (range, –6.17 to 5.01) and 4.42 (range, –2.72 to 11.56), respectively. 

“Overall QOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL who received liso-cel as second-line treatment,” presenting study author Jeremy Abramson, MD, director, Jon and Jo Ann Hagler Center for Lymphoma, associate professor of medicine, Massachusetts General Hospital Cancer Center, said during a presentation of the data. “These findings corroborated with previously reported health-related QOL associated with liso-cel treatment.” 

Abramson J, Solomon S, Arnason J, et al. Improved quality of life (QOL) with lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, compared with standard of care (SOC) as second-line (2L) treatment in patients (pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): results from the phase 3 TRANSFORM study. Poster presented at: 63rd American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA.

Oral Bruton tyrosine kinase inhibitors make notable strides in CLL treatment. Chimeric antigen receptor T-cell therapy continues to command attention by besting standard-of-care therapies. 

63rd American Society of Hematology Annual Meeting and Exposition: Major Nurse Takeaways 

The rise of the COVID-19 pandemic has dramatically increased staffing shortages and burnout among nursing professionals.

®, 3 experienced oncology nurses share their experiences working throughout the pandemic—particularly in light of the recent Omicron surge. The oncology nurses explain how their institutions have responded to the various crises, how staffing shortages have affected with the quality of care that patients receive and how, in their opinion, hospital administrators can work with nurses to create a more effective care delivery model moving forward.

Out of respect for the nurses’ privacy and their wishes, 

 has agreed to omit their names and institutions from the interview.

®: How long have you been working in health care?

I have been an oncology nurse for 25 years, since 1997.

I have been working in health care for 30 years.

What subspecialty of nursing do you currently work in?

I am an oncology nurse, with specialization in hematologic malignancies and advanced cancers. I have a clinical practice in the care of adults with these cancers. I also am a full-time faculty member and researcher at a prominent school of nursing and cancer center.

I work in oncology, in a bone marrow transplant (BMT)/chimeric antigen receptor therapy (CAR-T) outpatient setting.

How has your institution responded to the omicron surge?

I am not authorized to speak on specific policies at my University, however; what I am seeing and hearing is tremendous strain in our cancer centers across the country, both in inpatient and outpatient settings. The surge of COVID-19 cases has flooded inpatient settings, so patients have to wait longer for beds, tests, and inpatient treatments. Another impact is that, due to space constraints, patients with cancer may be admitted to non-oncology floors, so they are not benefiting from the specialized care that oncology nurses offer.

In the outpatient setting, clinics need to maintain physical distancing, so fewer infusion and treatment spaces are open. Shortages of nurses, phlebotomists, radiology, and pharmacy personnel, among others, translates to longer wait times for patients and the need to reschedule patients.

Many cancer centers have shifted to virtual visits for clinically stable patients who may not need a physical exam. Centers have also tried to redistribute patients to other settings within their system to reduce the pressure. Some centers are also rapidly launching home infusion services for certain patients who meet certain criteria.

As the staffing shortages persist or worsen, cancer centers are facing the tough decision of triaging treatment times for patients. This is very unsettling, as we want to deliver care to all patients we serve. Yet, it may not be possible to do so and some centers are drafting guidance principles for prioritizing appointments for cancer treatment.

I have observed that several local hospice services are not accepting new patients. This places a huge burden on the cancer care team to deliver exceptional end-of-life care to patients in a setting of reduced inpatient capacity and suboptimal options to manage patients outside of the inpatient setting.

 My institution has responded by pausing elective procedures, restricting the number of permitted visitors for inpatients (only 2 caregivers are allowed to visit hospice care), not allowing caregivers in infusion suites—except for in extenuating circumstances, allowing only 1 support person to attend in-person office visits. 

In addition, since the pandemic began, we require all visitors and staff to wear masks. We require all employees to be vaccinated as a condition of employment.

They have tried their best to increase both proactive and reactive testing for associates, but it has sometimes been difficult to schedule because you may have to wait on the phone with occupational health for over an hour.

Furthermore, it’s been difficult for people who have tested as positive outside the hospital at other clinics to report this to occupational health as follow-up. This places stress on management as well because many associates want to report positive tests only to their managers, who are not equipped to provide follow-up advice and clearance to return to work. The initial 2 weeks of the surge were extremely stressful on staff and resulted in increased staffing shortages for several weeks.

How has your institution responded to the staffing shortage?

Cancer centers are facing the harsh reality of having to operate with fewer personnel. In some cases, appointments need to be rescheduled or relocated, which is inconvenient to patients and families.

 In the inpatient setting, up to $10,000 sign-on bonuses have been offered for some open positions, travel nurses have been hired; MAs, CNAs, and student nurses in their junior/senior year have been hired to help the inpatient surge. Additionally, some registered nurses in non-clinical roles have been required to return to bedside roles in some capacity.

By increasing the rate at which they are offering travel nurses—sometimes up to $200/hour. There are also some efforts to make more positions flexible. For example, my institution currently allows more part-time positions as well as flexible sets of four 10-hour shifts, instead of a mandatory Monday through Friday. There are also some instances of remote working part-time options for positions that require a lot of patient coordination and patient triage outpatient. For example, example for nurse navigators or BMT coordinators.

I think this is critical to help the profession attract and attain nurses in the market looking for more flexible working hours due to family or more work/life balance overall. If institutions are able to do this, along with provide strong salaries and solid benefits (especially time off for vacation and sick leave) then I think staffing shortages will alleviate.

How has essential care been compromised by the lack of available nurses?

The field is in a perilous time. We are challenged with trying to deliver the very best care to patients and families, while we have staffing and resource constraints. That means less time for patient and family education, and [there is a lower] ability to monitor and act on treatment side effects.

Prior work on missed oncology nursing care has shown that care coordination with the cancer team is the second most frequent missed care item. In the current crisis, it's likely that coordinating care for patients and assuring safe discharges to home or other settings are more difficult. Visitor restrictions place an additional burden on patients and families as fewer loved ones can be by the patient's side during treatment. What we know from the literature is that when staffing levels are low, patients are less likely to receive needed ambulation, mouth care, assistance with toileting, and delayed medication administration.

Sometimes you have one nurse doing the role of 4 or 5 positions, especially in the outpatient setting. This means there are less patient education opportunities, providers (physicians, NP’s, etc.) are frustrated with slow patient coordination, and management is unhappy with slow growth of a program. Moreover, the staff that remains is burnt out. For patients waiting for a BMT, the timing of transplant is key to prevent relapse of disease. With no/low staff to coordinate, patients have to wait longer for essential services, such as transplant and CAR-T therapy.

How have the longer shifts negatively impacted both patients and employees in your institution?

As we see more staff vacancies, either due to turnover or COVID-19 exposure, management is often asking nurses to stay longer or pick up more shifts. We know that extra-long shifts are associated with higher likelihood of patient safety events and that additional overtime shifts contribute to higher levels of burnout. We need to be careful to spread this extra burden around equitably.

This pandemic has taught us that crisis may not resolve swiftly. It's okay for a nurse to decline to stay late or accept another shift to attend to their own needs and wellness. Nurses' mental health is really important to monitor and address right now.

Although the nurse-to-patient ratios have not changed, the ability to fill these ratios consistently has led to a higher patient load. Patients with cancer are extremely empathetic and understanding and see how hard the nurses are working and are hesitant to ask for anything! Nurses are exhausted and leave work feeling guilty for not doing more, but they’ve given all that they have. Experienced nurses have left the inpatient setting for non-clinical roles, positions in ambulatory care, or have retired completely, leaving a gap of knowledge that will not be able to be replaced.

[There is]definitely burnout and sometimes caregiver fatigue. You see staff leaving the hospital unhappy. When they reach home, they are too tired to spend quality time with their family and/or do important things such as exercise or cook healthy meals. I’m really worried about the overall physical and mental health of healthcare workers, especially those who are covering multiple positions.

In your opinion, what is the best way to alleviate the burden that is currently being placed upon nursing professionals?

 I challenge nurse leaders to critically examine the practice environments for oncology nurses: Have you down all that you can to reduce administrative burdens so that nurses have the majority of their time devoted to patient care? Have you streamlined documentation and other administrative tasks to the bare, required minimum? Have you engaged your nursing team in a discussion about how they want to practice? 

If we don't attend to these critical items, I fear the staff shortages we are experiencing now will only worsen. We can't wait to resolve this when the pandemic eases nor can we assume that things will return to normal. Now is the time for oncology nurses and their leaders to envision and enact a better care delivery model that serves patients, families, and clinicians.

One way is to allow more flexible schedules for all staff in regard to time; help is needed around the clock. If someone can work 3 am until 7 am, or noon until 5pm, let them!

Allow job sharing of all roles, rather than posting for permanent full-time—ask the staff what they want and what could help them and do it! Some experienced nurses who have resigned or retired would have liked to continue to work 1 or 2 days a week or part-time, work in a float position, or with telehealth visits, but they weren't allowed!

Administrators should reconsider allowing fully vaccinated/masked caregivers in the infusion centers. Family members are usually waiting in their cars in the parking lot so that they are close by, so why not let them come inside and get a blanket for their loved one, or get them a glass of water and therefore allow the nurses to monitor patients and triage calls?

Lastly, partner experienced nurses with novice nurses, we can learn a lot from each other. Revisit team nursing rather than primary nursing. Hire LPNs and ADNs. Pause accreditation visits.

 Employers need to do all they can to attract and attain staff. Listen to their concerns and act. Have impressive paid time off practices where employees can catch up on work life balance and feel they are valued for the extra hours they put in working. Also, employers need to pay well or other institutions will offer bonuses and better salaries and their employees will leave.

Seasoned oncology nurses share how the COVID-19 pandemic has affected the standard of care at their institution, the consequences of the staffing shortage, and how they believe the oncology community can work together to create a better working environment.

By ONN Staff

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