Concise Reviews of Studies Relevant to Hematology Oncology Pharmacy

JHOP - June 2018 Vol 8, No 2 - From the Literature
With Commentaries by Robert J. Ignoffo, PharmD, FASHP, FCSHP
Clinical Professor Emeritus, University of California, San Francisco; Professor of Pharmacy, College of Pharmacy, Touro University–California, Mare Island, Vallejo, CA
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In This Article

How Oncology Pharmacists Can Enhance Patient Quality of Care

BACKGROUND: The American Society of Clinical Oncology established the Quality Oncology Practice Initiative (QOPI) in 2006 to facilitate quality measurement of patient care, and to continuously improve cancer care. However, the extent to which pharmacists can affe ct patient care and its reimbursement through the QOPI metrics is unknown. Because pharmacists are a vital part of the care team, providing direct patient care and developing medication use guidelines and practice-based policies, a team of 3 pharmacists studied the 200 Fall 2016 QOPI measures for potential areas for pharmacist involvement.

METHODS: Among the 200 QOPI measures reviewed, the researchers analyzed 177 measures, which encompass disease- and domain-specific content areas. Using the Hematology/Oncology Pharmacy Association Scope of Practice document and a summary of oncology pharmacist services, they identified which practice domains and pharmacy services would be most appropriate for pharmacist involvement based on the selected QOPI measures.

RESULTS: A total of 67 (38%) metrics were identified as potential areas for pharmacist involvement. The majority of measures were related to optimizing drug therapy by creating and implementing pharmacy guidelines. The measures that pharmacists could intervene in successfully to improve quality of care pertained to symptom management, oral chemotherapy, and other measures regarding appropriate medication use and monitoring.

The 110 measures that were not deemed actionable for pharmacist intervention included documentation of patient-specific parameters, ordering of imaging, and genetic counseling. In addition, the researchers noted that 6 of the 16 oncology Merit-Based Incentive Payment System measures for 2017 aligned with 25 of the QOPI measures they identified that could benefit from pharmacist involvement.

“Our review demonstrates that multiple opportunities exist for pharmacists to directly impact the quality metrics that are measured by ASCO QOPI,” the researchers said.

“Practicing pharmacists have the education and training necessary to impact these measures as part of their current scope of work. Focusing new services and patient care activities to address validated quality metrics is a natural next step in the care that oncology clinical pharmacists provide to patients given the potential to improve patient care and enhance reimbursement for oncology practices,” they concluded.

Source: Vulaj V, Hough S, Bedard L, et al. Oncology pharmacist opportunities: closing the gap in quality care. J Oncol Pract. 2018 Jan 3. Epub ahead of print.

Commentary by Robert J. Ignoffo

This review by Vulaj and associates shows the potential for the impact of oncology clinical pharmacists on 67 QOPI quality metrics, which cover a substantial amount of care. The activities associated with these metrics generally fall into the realm of drug-related functions, an area of expertise familiar to pharmacists. By including an oncology clinical pharmacist on the healthcare team, a gap in quality care can be filled that could otherwise be missed by other healthcare professionals. However, more work is needed to show that oncology clinical pharmacists can truly make a difference in patient outcomes, especially those related to symptom management, oral chemotherapy, and other activities associated with appropriate medication use and monitoring. This research will require working with the healthcare team to identify new services and patient care activities that can improve patient outcomes and demonstrate financial gain.

A study by Ignoffo and colleagues showed that if board-certified oncology pharmacists were used to see patients for drug-related issues, these pharmacists could have between 2.5 million and 5 million 30-minute oncology visits by patients by 2020.1 If consistent outcomes can be shown for such pharmacist clinical activities, the gap in care quality will be narrowed.

  1. Ignoffo R, Knapp K, Barnett M, et al. Board-certified oncology pharmacists: their potential contribution to reducing a shortfall in oncology patient visits. J Oncol Pract. 2016;12:e359-e368.

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Metastasis-Free Survival for Prostate Cancer Longer with Apalutamide Than with Placebo

BACKGROUND: Androgen-deprivation therapy (ADT) with bilateral orchiectomy or drugs that suppress testosterone production is the mainstay of treatment for patients with metastatic prostate cancer, as well as for nonmetastatic prostate cancer. Although ADT is initially effective, it stops working in almost all patients with prostate cancer, leading to castration-resistant disease. Apalutamide is a nonsteroidal antiandrogen therapy that was developed for the treatment of prostate cancer. A phase 2 clinical trial of apalutamide treatment in men with nonmetastatic, castration-resistant prostate cancer (CRPC) at high risk for progression resulted in durable prostate-specific antigen (PSA) responses. In a phase 3 clinical trial, researchers evaluated the efficacy of apalutamide for metastasis-free survival in men with nonmetastatic CRPC and a PSA doubling time of ≤10 months.

METHODS: The international, randomized, double-blind, placebo-controlled, phase 3 SPARTAN trial included 1207 men with nonmetastatic prostate cancer that had stopped responding to ADT and had a rapid PSA doubling time. Patients were randomized 2:1 to apalutamide 240 mg daily (N = 806) or placebo (N = 401) and were evaluated every 16 weeks for signs of disease progression. ADT was continued for all patients. The primary end point was metastasis-free survival. Secondary end points included time to me­tastasis, progression-free survival (PFS), time to symptomatic progression, overall survival (OS), and time to cytotoxic chemotherapy initiation.

RESULTS: The median metastasis-free survival was >2 years longer in the apalutamide group (40.5 months) than in the placebo group (16.2 months). Time to metastasis, PFS, and time to symptomatic progression were significantly longer for patients who received apalutamide versus placebo (P <.001 for all comparisons). Furthermore, OS, time to the initiation of cytotoxic chemotherapy, and second PFS (ie, time from randomization to investigator-assessed disease progression) were longer with apalutamide than with placebo; the researchers noted that these particular findings support the clinical benefit of apalutamide.

The rate of adverse events leading to treatment discontinuation was <11% in both arms—10.6% with apalutamide and 7.0% with placebo. Apalutamide was associated with higher rates of fatigue (30.4%), rash (23.8%), weight loss (16.1%), arthralgia (15.9%), falls (15.6%), and fractures (11.7%) versus placebo. The majority of adverse events were grade 1 or 2.

“The consistent increase in metastasis-free survival associated with apalutamide across all patient subgroups…suggests that the clinical benefits of apalutamide extend to patients with a high disease burden,” the researchers said.

Source: Smith MR, Saad F, Chowdhury S, et al. N Engl J Med. 2018;378:1408-1418.

Commentary by Robert J. Ignoffo

This study shows that apalutamide substantially prolongs metastasis-free survival in patients with nonmetastatic CRPC. This is the only trial to date that has used a competitive inhibitor of the androgen receptor in this patient population. It was conducted in an international patient population, and in more than 330 institutions worldwide.

Of note, after 40 months of observation, 58% of patients were alive and without metastases. Furthermore, in a secondary analysis, 83% of the patients in the apalutamide arm versus 10% of those in the placebo arm were without PSA progression at 12 months. Side effects of apalutamide were primarily grade 1 and 2 and were well-tolerated. Only 11% of patients discontinued therapy because of adverse effects.

In conclusion, patients with high-risk, nonmetastatic CRPC should be offered apalutamide, which has been added to the National Comprehensive Cancer Network guidelines for this indication.

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Nivolumab plus Ipilimumab Combination Improves Overall Survival in Untreated Renal-Cell Carcinoma

BACKGROUND: Among patients with untreated or treated advanced renal-cell carcinoma (RCC), nivolu­mab plus ipilimumab resulted in an objective response rate of 40% and a 2-year overall survival (OS) of 67% to 70%, depending on the dose. Researchers recently reported updated results from the CheckMate-214 trial that compared the efficacy and OS benefit of nivolumab plus ipilimumab combination versus sunitinib monotherapy in previously untreated advanced RCC.

“Approximately 75% of patients with advanced renal-cell carcinoma have intermediate- or poor-risk disease and have worse outcomes than those with favorable-risk disease,” the researchers said. “Combination therapy with nivolumab plus ipilimumab has shown promising efficacy in multiple tumor types, resulting in higher rates of response than either agent alone, and is approved for the treatment of advanced melanoma.”

METHODS: CheckMate-214 was a randomized, open-label, phase 3 trial that included 1096 patients with advanced RCC, with 847 classified as intermediate- or poor-risk. Patients were randomized in a 1:1 ratio to treatment with intravenous nivolumab (3 mg/kg over 60 minutes) plus ipilimumab (1 mg/kg over 30 minutes) every 3 weeks for 4 doses followed by nivolumab monotherapy (3 mg/kg) every 2 weeks, or oral sunitinib 50 mg daily for 4 weeks of each 6-week cycle. The co-primary end points were objective response rate, progression-free survival (PFS), and OS.

RESULTS: After a median follow-up of 25.2 months, the 18-month OS was 75% with the combination versus 60% with sunitinib. The median OS was not reached for the combination immunotherapy arm versus 26.0 months for the sunitinib arm. The combination therapy also produced better rates of objective response and complete response (42% and 9%, respectively) compared with sunitinib (27% and 1%, respectively). The combination arm also demonstrated longer median PFS than the sunitinib arm (11.6 months vs 8.4 months, respectively; P = .03), but this was not significant because the between-group difference did not meet the prespecified threshold (P = .009).

The majority of patients in both treatment groups had treatment-related adverse events. Grade 3 or 4 events were less common in the combination arm than in the sunitinib arm (46% vs 63%, respectively). Adverse events that led to therapy discontinuation were reported in 22% of patients receiving nivolumab plus ipilimumab compared with 12% of patients receiving sunitinib.

Source: Motzer RJ, Tannir NM, McDermott DF, et al. N Engl J Med. 2018;378:1277-1290.

Commentary by Robert J. Ignoffo

The National Comprehensive Cancer Network guidelines list several medications that are indicated for the first-line treatment of patients with advanced RCC, including sunitinib. This phase 3 clinical trial by Motzer and colleagues compared the combination of oral nivolumab and ipilimumab with sunitinib regarding OS and PFS outcomes. The results were analyzed for 3 scenarios: intermediate- and high-risk patients, low-risk patients, and intention-to-treat patients.

Notably, the benefit in OS and response rate was seen only in the intermediate- and poor-risk cohorts. For the low-risk patients, the OS at 18 months with the combination was not different from that with sunitinib. Furthermore, the PFS and objective response rate were significantly higher with sunitinib than with nivolumab plus ipilimumab in the low-risk group. Although patients with ≥1% PD-L1 expression had a better PFS and higher objective response rate with the combination versus sunitinib, PD-L1 expression was not entirely predictive of response to, and OS benefit with, the combination. Grade 3 or 4 adverse events occurred in 46% of patients in the nivolumab plus ipilimumab arm and in 63% of patients in the sunitinib arm; adverse events led to discontinuation in 22% and 12% of patients, respectively. Of the 436 patients receiving nivolumab plus ipilimumab who had immune-mediated reactions, 35% received treatment with high-dose corticosteroids (prednisone ≥40 mg daily).

In summary, this study showed that nivolumab plus ipilimumab is more efficacious and provides a greater survival benefit than sunitinib in the treatment of patients with intermediate- and poor-risk advanced clear-cell RCC.

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