Continuing Education: December 2021

Release Date: December 22, 2021

Expiration Date: December 22, 2022

This activity is provided free of charge.

STATEMENT OF NEED
This CE article is designed to serve as an update on cancer detection and prevention and to facilitate clinical awareness of current and new research regarding state-of-the-art care for those with or at risk for cancer.

TARGET AUDIENCE
Advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients may participate in this CE activity.

EDUCATIONAL OBJECTIVES
Upon completion, participants should be able to:
1. Describe new preventive options and treatments for patients with cancer
2. Identify options for individualizing the treatment for patients with cancer
3. Assess new evidence to facilitate survivorship and supportive care for patients with cancer

ACCREDITATION/CREDIT DESIGNATION STATEMENT
Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 0.5 Contact Hour.

DISCLOSURES/RESOLUTION OF COI
It is the policy of Physicians' Education Resource®, LLC (PER®) to ensure the fair balance, independence, objectivity, and scientific objectivity in all of our CE activities. Everyone who is in a position to control the content of an educational activity is required to disclose all relevant financial relationships with any commercial interest as part of the activity planning process. PER® has implemented mechanisms to identify and resolve all conflicts of interest prior to release of this activity.

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial interests pertaining to this activity.

METHOD OF PARTICIPATION
1. Read the articles in this section in their entirety.
2. Go to www.gotoper.com/go/December
3. Complete and submit the CE posttest and activity evaluation.
4. Download/Print your CE Certificate

OFF-LABEL DISCLOSURE/DISCLAIMER
This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical nursing purposes only and is not meant to substitute for the independent medical judgment of a nurse or other health care provider relative to diagnostic, treatment, or management options for a specific patient's medical condition.

The opinions expressed in the content are solely those of the individual authors and do not reflect those of PER®

Table of Contents

Multiple Myeloma: Daratumumab-Lenalidomide-Dexamethasone Combination May Become Preferred Treatment for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma

Cervical Cancer: Adding Pembrolizumab to Chemotherapy May Be
New Standard of Care for Frontline Treatment of Advanced Cervical Cancer

Daratumumab-Lenalidomide-Dexamethasone Combination May Become Preferred Treatment for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma

“Due to the favorable efficacy and safety profiles of daratumumab plus lenalidomide and dexamethasone, investigators speculate that the combination may become the new standard of care in multiple myeloma treatment.”

By Darlene Dobkowski, MA

Recent findings showed that older patients with newly diagnosed multiple myeloma demonstrated progression-free survival (PFS) and superior overall survival (OS) when treated with daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) compared with lenalidomide and dexamethasone (Rd).

The presentation at the International Myeloma Society’s 18th International Myeloma Workshop, held September 8 to 11, 2021, in Vienna, Austria, focused on updated efficacy and safety data for D-Rd compared with Rd at a median follow-up of nearly 5 years in the phase 3 MAIA study (NCT02252172). The updated results, part of a prespecified interim OS analysis, followed a primary analysis that occurred at a median follow-up of 28 months.2

“Those results, when looking at D-Rd, both for PFS and OS and a relatively good safety profile, I would say, are now establishing D-Rd as a new standard of care for patients [who] are not transplant eligible,” said Philippe Moreau, MD, professor of clinical hematology at University Hospital Hôtel-Dieu in Nantes, France, in a presentation of the findings.

Investigators analyzed data from 737 patients with newly diagnosed multiple myeloma. These patients were ineligible for high-dose chemotherapy and autologous stem cell transplantation because of their age (>65 years) or the presence of comorbidities. Patients were randomly assigned to receive D-Rd (n = 368) or Rd (n = 369). Patients had a median age of 73 years (range, 45-90 years). The primary end point was PFS, with key secondary end points including OS, among others. Longer treatment times resulted in much greater differences in PFS between the D-Rd and Rd groups. There was no significant difference in median PFS between D-Rd and Rd among patients either treated for less than 9 months or treated for 9 to 18 months (P = .3579 and P = .2480, respectively), but D-Rd produced a robust benefit in patients treated longer than 18 months (median PFS not reached and 54.8 months, respectively; HR, 0.57; 95% CI, 0.43-0.76; P < .0001). The 5-year PFS rates among patients treated longer than 18 months were 64.4% and 44.6%, respectively.

At a median follow-up of 56.2 months, the D-Rd group had a significant 32% reduction in the risk of death compared with the Rd group.Median OS was not reached in either group (HR, 0.68; 95% CI, 0.53-0.86; P = .0013). The estimated 5-year OS rate was 66.3% in D-Rd group group compared with 53.1% in the Rd group.Median PFS was not reached in the D-Rd group, whereas those assigned to Rd had a median PFS of 34.4 months (HR, 0.53; 95% CI, 0.43-0.66; P < .0001).

Longer follow-up did not yield new safety concerns. The most common grade 3 or 4 treatment-emergent AE was neutropenia, occurring in 54.1% of patients in the D-Rd group and 37.0% in the Rd group. Patients in the D-Rd group tended to remain on treatment longer than those in the Rd arm, with median treatment durations of 47.5 months and 22.6 months and with 42% vs 18% of patients remaining on study treatment, respectively. Patients in the D-Rd arm were less likely than the Rd arm to discontinue due to disease progression (27% vs 34%) or adverse events (AEs) (13% vs 23%).

Reference

Moreau P, Facon T, Kumar SK, et al. Overall survival and progression-free survival by treatment duration with daratumumab + lenalidomide/dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study. Presented at: 18th International Myeloma Workshop; September 8-11, 2021; Vienna, Austria. Oral abstract session. Accessed September 7, 2021. https://virtual.imw2021.org/live-stream/19803771/Oral-Abstract-Session

Facon T et al. N Engl J Med. 2019;380(22):2104-2115

Adding Pembrolizumab to Chemotherapy May Be
New Standard of Care for Frontline Treatment of Advanced Cervical Cancer

Data presented at the ESMO Congress 2021 suggest that pembrolizumab in addition to
chemotherapy with or without bevacizumab may become new standard of care in the frontline
setting of cervical cancer treatment.

By Kristi Rosa

Adding pembrolizumab (Keytruda) to chemotherapy with or without bevacizumab (Avastin) was shown to effectively improve survival rates patients with persistent, recurrent, or metastatic cervical cancer in the phase 3 KEYNOTE-826 trial (NCT03635567). Data from the trial’s first interim analysis were presented as part of the Presidential Symposium during the European Society for Medical Oncology (ESMO) Congress 2021, held September 16 to 21, 2021.

Platinum-based chemotherapy has been the standard treatment for patients with persistent, recurrent, or metastatic cervical cancer, with the preferred regimen being platinum-based chemotherapy, paclitaxel, and bevacizumab. Although prior studies have demonstrated the efficacy of PD-1 inhibitors, such as pembrolizumab and cemiplimab (Libtayo), as monotherapy in patients with previously treated cervical cancer, no data have been available regarding whether the addition of a PD-1 inhibitor to chemotherapy, with or without bevacizumab, would improve outcomes. To this end, investigators launched the double-blind KEYNOTE-826 trial, which enrolled patients with persistent, recurrent, or metastatic cervical cancer that was not amenable to curative treatment.

In the subset of patients with a PD-L1 combined positive score (CPS) of 1 or higher, the median progression-free survival (PFS) in the investigative (PEM) and control (PBO) arms was 10.4 months (95% CI, 9.7-12.3) vs 8.2 months (95% CI, 6.3-8.5), respectively (HR, 0.62; 95% CI, 0.50-0.77; P < .001). Median overall survival (OS) was not reached (NR; 95% CI, 19.8-NR) at the time of data cutoff in the PEM arm vs 16.3 months (95% CI, 14.5-19.4) in the PBO arm (HR, 0.64; 95% CI, 0.50-0.81;P < .001).

In the all-comers population, the median PFS was 10.4 months (95% CI, 9.1-12.1) in the PEM arm vs 8.2 months (95% CI, 6.4-8.4) in the PBO arm (HR, 0.65; 95% CI, 0.53-0.79; P < .001). The median OS in this population was 24.4 months (95% CI, 19.2-NR) with pembrolizumab vs 16.5 months (95% CI, 14.5-19.4) with placebo (HR, 0.67; 95% CI, 0.54-0.84; P < .001).

In the group of patients who had a PD-L1 CPS of 10 or higher, the median PFS with pembrolizumab plus chemotherapy with or without bevacizumab was 10.4 months (95% CI, 8.9-15.1) vs 8.1 months (95% CI, 6.2-8.8) with chemotherapy with or without bevacizumab (HR, 0.58; 95% CI, 0.44-0.77; P < .001). The median OS was also NR (95% CI, 19.1-NR) in the PEM arm vs 16.4 months (95% CI, 14.0-25.0) in the PBO arm (HR, 0.61; 95% CI, 0.44-0.84; P = .001).

“Adding pembrolizumab to chemotherapy with or without bevacizumab provides statistically significant, clinically meaningful improvements in PFS and OS in patients with persistent, recurrent, or metastatic cervical cancer. The significant benefit was observed in all primary analysis populations and was generally consistent across protocol-specified subgroups,” lead study author Nicoletta Colombo, MD, director of the Gynecologic Oncology Division at the European Institute of Oncology and associate professor of obstetrics and gynecology at the University of Milan-Bicocca in Milan, Italy, said in a presentation of the findings. “Data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care for the treatment [of patients with this disease].”

Eligible patients had an ECOG performance status of 0 or 1 and could not have previously received systemic chemotherapy. Prior radiotherapy and chemoradiotherapy were allowed. A total of 617 participants were randomized 1:1 to receive pembrolizumab at 200 mg every 3 weeks for up to 35 cycles plus paclitaxel and cisplatin or carboplatin every 3 weeks for up to 6 cycles with or without bevacizumab at 15 mg/kg every 3 weeks (n = 308). The PBO arm (n = 309) received the same regimen, but with placebo instead of pembrolizumab. Patients in both arms had the option of adding bevacizumab to their regimen, and 63.1% received this drug.

Stratification factors included metastatic disease at diagnosis (yes vs no), PD-L1 CPS (<1 vs 1 to <10 vs ≥10), and planned bevacizumab use (yes vs no). The dual primary end points of the study were investigator-assessed OS and PFS per RECIST v1.1 criteria; secondary end points comprised overall response rate, duration of response, 12-month PFS, and safety. Patient-reported outcomes were evaluated using the EuroQoL EQ-5D-5L Visual Analog Scale (VAS) score and served as an exploratory end point In the all-comers population, the median age between the arms was 50.5 years (range, 22-82). Moreover, 43.3% of patients had an ECOG performance status of 1, 72.3% had squamous cell disease, and 48.3% had previously received chemoradiation or radiation.

The safety profile of the pembrolizumab regimen was manageable. The rates of all-cause and treatment-related grade 3 or higher and serious adverse events (AEs) were all numerically greater in the immunotherapy-containing arm. However, patients receiving pembrolizumab were generally on treatment longer than those receiving placebo, according to Colombo.

The most frequent all-cause AEs of any grade reported on the PEM and PBO arms included anemia (61.2% vs 53.4%), alopecia (56.4% vs 57.9%), nausea (39.7% vs 43.7%), diarrhea (35.5% vs 29.8%), and fatigue (28.7% vs 27.2%), among others. The most common immune-mediated AEs of any grade were hypothyroidism (18.2% vs 9.1%) and hyperthyroidism (7.5% vs 2.9%, respectively).

“Approximately one-third of patients on the [PEM] arm discontinued any treatment component due to an AE,” Colombo said. “The incidence of AEs leading to death [was] similar in the treatment arms. The incidence of immune-related AEs was higher in the [PEM] arm.”