The fixed-duration treatment of venetoclax (Venclexta) plus obinutuzumab (Gazyva) continued to deliver long-term survival benefit for unfit patients with chronic lymphocytic leukemia (CLL) with coexisting conditions, according to updated efficacy and safety data from the ongoing phase 3 CLL14 trial (NCT02242942) presented during the 2022 EHA Congress.

At a median follow-up of 65.4 months, the median progression-free survival (PFS) for patients treated with venetoclax plus obinutuzumab was not reached (NR) compared with 36.4 months among patients treated with chlorambucil (Leukeran) plus obinutuzumab (HR, 0.35; 95% CI, 0.26-0.46; 

 < .0001). The 5-year PFS rates were 62.6% and 27.0%, respectively. Most patients treated with fixed-duration venetoclax plus obinutuzumab (63%) remain without a PFS event 4 years post treatment.

“What is important for us in these longer follow-ups is to really understand what happens with the disease dynamics and what happens with the patients when they get off treatment,” Othman Al-Sawaf, MD, a physician at the University Hospital of Cologne in Germany said in a presentation of the findings.

PFS benefits with venetoclax plus obinutuzumab were also observed across subgroups. The median PFS for patients without a 

 deletion or mutation was NR in the investigational arm compared with 38.9 months in the control arm. Patients with a 

 deletion or mutation experienced a median PFS of 49.0 months and 19.8 months, respectively.

 status the median PFS was NR in the investigational arm compared with 59.9 months in the control arm. The median PFS for patients with unmutated IGHV was 64.2 months and 26.9 months, respectively.

The CLL14 study enrolled patients with previously untreated CLL and coexisting medical conditions deemed unfit, who were randomly assigned 1:1 to receive either venetoclax plus obinutuzumab (n = 216) or chlorambucil plus obinutuzumab (n = 216). To be eligible for the trial, patients needed to have a total cumulative illness rating scale (CIRS) score greater than 6 and/or a creatine clearance of less than 70 mL/min.

Patients in the venetoclax arm were treated with 12 cycles of venetoclax administered in a ramp-up dosing schedule with 6 cycles of obinutuzumab. In the control arm, patients received 12 cycles of chlorambucil with 6 cycles of obinutuzumab.

The primary end point was PFS. Key secondary end points included response, minimal residual disease (MRD), and overall survival (OS).

Baseline patient characteristics were well balanced between the 2 arms; the median age was 72 years and 71 years in the venetoclax plus obinutuzumab and chlorambucil plus obinutuzumab arms, respectively. The median total CIRS score were 9 (range, 0-23) and 8 (range, 1-28), respectively. The median estimated creatine clearance was 65.2 mL/min and 67.4 mL/min, respectively.

Patients in the investigational arm had low (14%), intermediate (64%), and high (22%) tumor lysis syndrome (TLS) risk. Patients also had Binet stage A (21%), B (35%), and C (44%) disease. Comparatively, patients in the control arm mostly had an intermediate TLS risk (68%) and Binet stage C disease (43%).

Most patients in both the investigational and control arms had unmutated 

 (61% vs 59%). Twelve percent of patients in both arms had deleted and/or mutated 

. Common cytogenic subgroups included deletion in 11q (17% vs 18%), trisomy in 12 (17% vs 19%), no abnormalities (24% vs 20%), and deletion in 13q alone (34% vs 36%).

Additional findings from the trial showed that the median time to next treatment (TTNT) was NR in the venetoclax arm compared with 52.9 months in the control arm. The 5-year TNNT rates were 72.09% and 42.84%, respectively (HR 0.42; 95% CI, 0.31-0.57; 

Thirty-one patients in the venetoclax arm progressed to a second line of treatment compared with 94 patients in the chlorambucil plus obinutuzumab arm. Most of these patients in both arms subsequently received a Bruton tyrosine kinase (BTK) inhibitor as their second line therapy (58.1% vs 54.3%). PI3K inhibitors and CD20 antibodies were used in 1 patient each, both in the chlorambucil plus obinutuzumab arm. Chemotherapy or chemoimmunotherapy were used as a second line treatment in less than a third of patients in both arms (25.8% vs 30.9%).

Notably, the median OS was NR in either arm. The 5-year OS rates were 81.9% and 77.0% in the investigational and control arms, respectively (HR 0.72; 95% CI, 0.48-1.09; 

Additionally, a longitudinal MRD assessment found that 4 years after treatment with venetoclax plus obinutuzumab 18.1% of patients had sustained MRD of less than 10-4. In the other arm, 1.9% of patients treated with chlorambucil plus obinutuzumab experienced sustained MRD of less than 10-4 4 years after therapy.

The depth of remission beyond 10-4 correlates with long-term PFS, which indicates the value of ultra-sensitive MRD assessments, Al-Sawaf noted. Patients treated with venetoclax plus obinutuzumab with MRD of at least 10-4 experienced a shorter OS compared with those with MRD less than 10-4.

In terms of safety, the most common adverse events (AEs) grade 3 or higher that occurred with venetoclax plus obinutuzumab included neutropenia (51.9%), thrombocytopenia (14.2%), anemia (7.5%), and febrile neutropenia (4.2%). After treatment, common grade 3 or greater AEs included neutropenia (4%), pneumonia (3.0%), and anemia (2%).

In the chlorambucil plus obinutuzumab arm, the most common grade 3 or higher AEs reported during treatment included neutropenia (47.2%), thrombocytopenia (15%), and infusion-related reactions (9.8%). After treatment, common grade 3 or higher AEs included neutropenia (1.9%), pneumonia (1.4%), and anemia (0.5%).

Secondary primary malignancy (SPM) events occurred in 55 patients and 44 patients in the investigational and control arms, respectively. Patients had at least 1 SPM at a rate of 20.8% and 15.0%, respectively. Common SPMs included non-melanoma skin cancer (9.0% vs 8.4%), solid organ tumors (7.1% vs 4.7%), and melanoma (3.8% vs 1.4%). Investigators noted that there was no statistical difference in the cumulative incidence of SPMs between the 2 arms.

“So far, there were no new safety signals [with venetoclax plus obinutuzumab],” Al-Sawaf concluded. “Secondary malignancies remain statistically not significant between the arms, but [we will] continue to follow-up on safety and survival in this study.”

Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5- year results of the randomized CLL14 study. Presented at: 2022 EHA Congress; June 9-17, 2022; Vienna, Austria. Abstract S148

Articles

An updated safety and efficacy analysis of the ongoing CLL14 trial showed that venetoclax plus obinutuzumab continues to be an effective treatment for patients with chronic lymphocytic leukemia and coexisting conditions.

Venetoclax/Obinutuzumab Continues to Show Efficacy in Unfit Patients with CLL 

Each month, we take a look back at the most popular 

Topics from June 2022 include the evolving role of social media in bridging patients together, nurse perspectives on future directions in CAR T-cell therapy development, and the potential limitations surrounding the CDC’s newly proposed opioid prescribing guidelines. Other top stories include a conversation with Ohio End of Life Options founder and executive director, Lisa Vigil Schattinger, MSN, RN, about her personal experience with medical aid in dying and ongoing research to determine whether music can help reduce chemotherapy-induced nausea.

5. The Future of CAR T-Cell Therapy: Will Off-the-Shelf Options Soon Enter the Playing Field?

Approval of off-the-shelf CAR T-cell therapy options may provide greater accessibility and benefit to patients according to experts. In this feature, 

 speaks with Brittney Baer, BSN, RN, and Kelly Garvin, BSN, RN, OCN, about the evolution of CAR T-cell therapy options and whether off-the-shelf options may become available in the near future.

4. Does the CDC’s Proposed Opioid Prescribing Guideline Fall Short on Drug Testing?

Although the CDC has put forth a strong effort to improve its opioid guidelines, many providers still feel that more can be done. In this feature story, Jack Kain, PharmD, discusses the recent changes to clinical guidelines and what questions remain surrounding optimal care with opioid therapy.

3. What Oncology Nurses Should Understand About Medical Aid in Dying

Lisa Vigil Schattinger, MSN, RN, discusses her experience with medical aid in dying, and what oncology nurses need to understand when supporting patients at the end of their lives.

2. Prescribing 20 mg of Mozart for Chemotherapy-Induced Nausea

Might the day come when the oncology nurse delivers acetaminophen alongside 20 mg of Mozart? Hear from Jason Kiernan, PhD, RN, ACNP, a Michigan State University investigator, who is preparing to expand on an encouraging pilot study that used a music-listening intervention to influence chemotherapy-induced nausea.

How Social Media Helps AYA Patients With Cancer Find Support

The rise of social media platforms has helped foster a community for adolescent and young adult patients with cancer. Hear as our partners with CancerCare outline how social media can positively fill a unique social need for this patient population.

To stay on top of all the latest news and features

Each month, we take a look back at the most popular Oncology Nursing News® stories. Here are the top 5 stories from June 2022.

Oncology Nursing News Top Stories: June 2022

Lindsay Fischer is the Associate Editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

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

Microvascular free tissue transfer with reconstruction has been in practice for 40 years now since its introduction in the early 80s, according to Eitan Prisman, MD, MA, FRCSS. 

 However, Prisman noted that accuracy and quality-of-life outcomes with reconstruction continue to represent an unmet need in head and neck cancer care.

Prisman, who is an associate professor of otolaryngology and head and neck surgery at the University of British Colombia, discussed the challenges of the standard practice during the 2022 Annual Supportive Care in Cancer conference. He also discussed how the application of virtual planning tools for surgical reconstruction may improve outcomes for patients with head and neck cancer.

“[During the procedure] we have a resected segment of the mandible or maxilla that we need to take free tissue transfer from other parts of the body with a microvascular suturing of the vessels. When we construct the mandible and maxilla, it’s really key to do it accurately so that we can restore not just cosmesis but function—swallowing, chewing, [and] breathing,” he said.

“[But] not all reconstructions are accurate. There’s [approximately] a 5% to 30% rate of nonunion of the bony reconstruction. There’s a 20% rate of plate extrusion. [And there are] a lot of things that we still do not completely comprehend in terms of patient’s quality of life after surgery. [However], a lot of software has been introduced to try to improve these reconstructions.”

Enter virtual surgical planning (VSP) into the equation, he said.

VSP is an important tool for oncologic osseous reconstruction of the mandible and midface, which is considered to be more precise than traditional methods.

 VSP begins with a CT scan, which allows surgeons to develop a 3-dimensional (3D) model of the mandible and radiologically define the segments of jaw that should be removed in order to achieve the preferred oncological ablation. When virtually preplanning, surgeons have as much time as they need, as well as the assistance of available mathematics and software to optimize a reconstruction plan.

After the resection is planned and defined in the virtual space, surgeons can print a 3D print cutting guide. “Once we commit to a virtual reconstruction, we can create a cutting guide for the fibula,” he said. “We print it on a 3D printer, sterilize it, bring it into the operating room, place it on the patient’s fibula and perform the cuts in the slots in order to achieve that optimal reconstruction.”

“Because virtual surgical planning allows surgeons to take time to curate a reconstruction guide to help them in the operating room, it allows for shorter surgery times,” Prisman said.

He shared a chart showing that the operation room time in minutes between patients whose surgeons used VSP for maxillary surgery (n = 10) and those who did not (n = 18), was 256 minutes vs 448 minutes, respectively. Further, the percentage of patients who needed tracheotomy was 20% vs 72%, respectively. The deviations between the plan and execution in surgery was a mean Δ mm of 7.5 vs 11.7.

“Historically, because the surgeries were longer there was more edema, we would [use a tracheostomy tube on] every one of our patients, [but] now our trach rate is approximately 20%,” Prisman said. “We rarely trach patients now because the surgeries are so much shorter. In addition, the length of [hospital] stay has decreased.”

Similarly, the literature suggests that VSP is associated with favorable outcomes in mandibular surgery as well.2 One study found that the mean distance between the actual mandibular osteotomy compared with the virtual mandibular osteotomy was 2.00 ± 1.12 mm.

 In a closer analysis of the fibular segments, with mean distance between the 2 was 1.30 ± 0.59 mm and the mean percentage overlap of actual plate to virtual plate was 58.73% ± 8.96%.

In a chart of mandible benefits that Prisman shared in his presentation, the deviations between the plan and execution in mandibular width, projection, and volumetric overlap were 2.32 ± 3.91, 2.39 ± 1.72, and 0.59 ± 0.51 mm respectively.

 There was also a significant reduction in operative time and length of stay, and no significant difference in complication rates.

Further, the non-union rates were 7.3% and 18.8%, respectively.

“Anyone who does dental implants knows that we can’t implant the patient that doesn’t achieve union,” explained Prisman. “With virtual surgical plans, [it is] much more common to achieve union compared [with] freehand surgery, and that’s because we’re optimizing the variables that we can control.”

“Are we accurate [with VSP]?” he asked. “We pretty much are: our width and projection and volume overlap is within 2 mm.”

VSP allows surgery to feel more confident that everything will go according to plan, he concluded. It represents a good opportunity to improve accuracy.

One potential complication of VSP that Prisman noted is its relationship to increased cost. The planning, model, and cutting guides can result in an increased surgical procedure costs; however, some experts not that less time in surgery may results in decreased operating room use charges.

 The cost analysis is an ongoing debate and will most likely continue to be an area of further focus and examination.

1. Prisman E. Virtual surgical planning in maxilla and mandible reconstruction. Presented at: 2022 Supportive Care in Cancer Annual Meeting; June 23-25, 2022; Toronto, Ontario.

2. Myers PL, Nelson JA, Rosen EB, Allen RJ Jr, Disa JJ, Matros E. Virtual surgical planning for oncologic mandibular and maxillary reconstruction. 

. 2021;9(9):e3672. doi:10.1097/GOX.0000000000003672

3. Rosen EB, Allen RJ Jr, Nelson J, Matros E. Inset guide for the osteocutaneous fibula flap with endosseous implants in oncologic jaw reconstruction. 

. 2019;7(10):e2475. Published 2019 Oct 10. doi:10.1097/GOX.0000000000002475

4. Wang E, Durham JS, Anderson DW, Prisman E. Clinical evaluation of an automated virtual surgical planning platform for mandibular reconstruction. 

. 2020;42(12):3506-3514. doi:10.1002/hed.26404

Mandible reconstruction and maxilla reconstruction surgeries might be optimized with virtual surgical planning, according to an expert speaker at the 2022 Supportive Care in Cancer Annual Meeting.



Virtual Planning For Surgical Reconstruction May Improve Outcomes for Patients With Head and Neck Cancer

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

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



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

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

At the 2022 Supportive Care in Cancer Annual Meeting, Jeffrey Crawford, MD, highlighted the potential value of biosimilars in reducing gaps in care for the treatment of febrile neutropenia. 

Biosimilars May Reduce Disparities in Febrile Neutropenia Treatment

Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

Data from the phase 1/2 EPCORE NHL-2 trial suggest that the combination of epcoritamab and R-CHOP is both effective and manageable in treating patients with high-risk diffuse large B-cell lymphoma.

Frontline Epcoritamab/R-CHOP Combination Induces 100% ORR in Patients With High-Risk DLBCL

Utilization of specialty nurse practitioner driven teams and use of individualized pain protocols for patients admitted with vaso-occlusive pain crisis improves quality of life for patients with sickle cell disease, and decreased hospital stay times.

Implementation of Individualized Pain Management in Vaso-occlusive Pain Crisis 

The FDA has approved lisocabtagene maraleucel as a second-line treatment for patients with relapsed or refractory large B-cell lymphoma. 

FDA Approves Liso-Cel for Second-Line Large B-Cell Lymphoma 

Updated data from the phase 3 BELIEVE trial revealed a sustained reduction in the need for red blood cell transfusions among patients with β-thalassemia who received treatment with luspatercept-aamt.

Luspatercept Linked With Maintained Reduction in Transfusion Dependence Among Patients With β-Thalassemia

This year’s congress showcased strategies for communicating sensitive topics, patient experiences with immunotherapy treatments, updates in the utility of
medical cannabis, and more. 

ONS Annual Congress Focuses on Increasing Nurse Comfort and Patient Understanding in Cancer Care

Laura J. Zitella, MS, RN, ACNP-BC, AOCN, recounts key nursing considerations with targeted therapy for chronic lymphocytic leukemia, and third-line diffuse large b-cell lymphoma options.  

Zitella Weighs In On Overarching Treatment Strategies in Hematologic Malignancies

This year’s conference highlighted advances in natural killer cells, CD39 and KRAS G12C inhibitors, and CAR T-cell therapies. 

A Quick Look at the 2022 AACR Annual Meeting

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

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

Heavily pretreated pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia maintained response with tisagenlecelucel according to long-term follow-up data from the phase 2 ELIANA trial. 

Pediatric/Young Adult Patients With B-ALL Continue to Derive Benefit From Tisagenlecluecel at 5-Year Follow-Up

Dr. Jackson is a certified oncology and bone marrow transplant clinical nurse specialist with clinical expertise in hematology/stem cell transplantation/cellular therapy. She is currently unit director–providing oversight of the clinical and fiscal operations of an inpatient hematology unit. Dr. Jackson is also a member of the National Association of Clinical Nurse Specialist, American Asociation of California Nurse Leaders, and the Oncology Nurses Society.

Approximately 140 in 100,000 pregnant women receive a cancer diagnosis. Of these diagnoses, 0.1% are considered malignant tumors.

Caring for a Pregnant Patient With Cancer

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

Top Medical News

Venetoclax/Obinutuzumab Continues to Show Efficacy in Unfit Patients with CLL

Oncology Nursing News Top Stories: June 2022

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

Virtual Planning For Surgical Reconstruction May Improve Outcomes for Patients With Head and Neck Cancer

Oncology Nursing News’ Top ASCO Picks

Most Recent