April 2019 Edition Vol.12, Issue 4

Reducing and Monitoring Chemotherapy Toxicities: A Fundamental Pillar to Improving Quality and Reducing Costs in Cancer Care

By Gary Binder, Sr. Director, HEOR & Value-Based Medicine, Helsinn Therapeutics US, Inc.


As cancer treatments advance into ever-narrower, more precise, and more costly regimens, the need remains high for feasible strategies to improve quality and lower costs. With acute care representing the largest component of cancer costs,1 multiple studies suggest that avoiding, monitoring, and limiting common side effects of chemotherapy may pose the greatest opportunity to reduce acute care services, yielding benefits in terms of costs, quality, and survival.2,3

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and costly of these drivers of avoidable acute care.3 However, multiple factors cause considerable shortfalls in use of proven methods to avoid CINV.

Recent research illuminates these gaps in care and their impact on outcomes and cost. Resolving these gaps will require acknowledgement of their magnitude, and informed action to implement proven and practical tactics. The opportunity exists to achieve sizable gains in cost and quality of cancer care – and to conserve limited resources that can be re-applied to therapeutic intervention.

Impact of chemotherapy toxicities

Two landmark findings in 2017 contributed to oncologists’ understanding of the impact of chemotherapy toxicities on the costs and quality of cancer care.

First, in one of the largest studies ever conducted in cancer, the Centers for Medicare & Medicaid Services (CMS) evaluated over 300,000 patients in the 30 days following chemotherapy administration. The prevalence of acute care utilization (emergency department or inpatient hospitalization) involving one or more of 10 toxicities (Table 1) was assessed.3

The 10 toxicities were identified by an expert panel as “avoidable” causes of acute care use post-chemotherapy. Acute care use related to these toxicities occurred in 20% of patients undergoing chemotherapy. As a result, CMS instituted the first oncology outcomes measure, OP-35, and mandated that each hospital providing outpatient chemotherapy publicly report their experience and have their Medicare reimbursement raised or lowered depending on how their results compared to national averages. 

Second, in a plenary session at ASCO 2017, Dr. Ethan Basch presented results of his randomized trial showing that regular monitoring of 12 chemotherapy toxicities, including four overlapping with the CMS research (diarrhea, emesis, pain, and nausea), led to reductions in acute care use, improved quality of life, and 5 months increased survival.2

The findings from these two studies suggest that there is ample opportunity to improve cancer care quality and reduce costs by focusing on chemotherapy toxicities that are both principal drivers of avoidable resource use and cost, as well as contributors to improved quality of life and survival when prevented or caught and managed early.

Of these toxicities, pain is the most common3 and arguably the most impactful; however, given the existing high level of attention to pain, new action steps for cancer care may best focus on the other three overlapping toxicities, all gastrointestinal: diarrhea, emesis, and nausea.

Due to the limited available treatments to prevent or manage diarrhea, and its ranking as the least prevalent among the OP-35 toxicities,3 researchers at several National Comprehensive Cancer Network (NCCN) centers and other institutions studied these toxicities and focused their outcomes research on chemotherapy-induced nausea and emesis (CINV).

Focusing in on CINV

Historically, CINV has been one of the most challenging aspects of cancer treatment. Some forms of classic chemotherapy (e.g., platinum-based regimens) cause emesis and nausea in most patients within five days following chemotherapy administration, often leading to treatment interruptions and poor outcomes. The early 1990s introduction of 5-HT3 receptor antagonists (RAs) as prophylaxis for CINV, and the subsequent 2003 introduction of neurokinin 1 (NK1) RAs, were widely adopted and heralded by ASCO as among the top five advances in oncology.4

National cancer guidelines uniformly recommend these agents along with dexamethasone for highly emetogenic chemotherapy (HEC), which represents roughly one-sixth of infused chemotherapy regimens,5 and for some patients receiving moderately emetogenic chemotherapy (MEC). NK1 RAs are not recommended for most MEC therapy unless the patient has specific risk factors likely to lead to CINV such as female gender, young age, history of CINV, morning sickness, or motion sickness.6

In a study presented at the 2019 NCCN Annual Conference, researchers evaluated electronic health records data for more than 90,000 courses of chemotherapy from 2012-2018 to assess acute care use in the 30 days post-chemotherapy, and the levels of physician adherence to antiemetic prophylaxis guidelines for HEC as well as for non-HEC chemotherapy.7

All-cause acute care use was observed in roughly 30% of patients receiving HEC and in 20% of non-HEC cases. For HEC, three-quarters of all-cause acute care utilization involved one or more of the 10 toxicities linked by CMS to potentially avoidable acute care, suggesting that CMS performed well in selecting these impactful toxicities. CINV was a factor in about one-third of the acute care cases involving HEC.

With CINV consistently ranking among patients’ most feared and debilitating toxicities of chemotherapy, and with long-established guidelines recommending triple antiemetic prophylaxis for HEC, one might expect near-complete levels of physician adherence to these guidelines. However, researchers found overall physician prophylaxis adherence was only 65% to 75% for two of the most commonly used HEC chemotherapies: cisplatin and anthracycline + cyclophosphamide (AC). Carboplatin AUC>4 was used with triple prophylaxis in only 14% of cases prior to its classification as HEC in 2017; this level rose to 20% by late 2018.

Addressing gaps in physician adherence to antiemetic guidelines

This average gap in overall physician adherence to the antiemetic guidelines masks a marked disparity among the adherence rates for individual physicians. The researchers evaluated antiemetic adherence rates for physicians administering more than five courses of HEC chemotherapy during the study’s time period and found that a substantial proportion of physicians adhered to guidelines for >90% of patients receiving cisplatin or AC, suggesting that 90% is a feasible target for physician compliance. However, most physicians fell well short of that level, with a considerable degree of variation between individual physicians.8

Gaps in physician adherence to antiemetic guidelines in HEC were consistent across tumor types, suggesting that oncologist specialty was not a factor in non-adherence. The researchers proposed several factors as contributors to the substantial gap in most oncologists’ adherence to antiemetic guidelines.

First, there may be incomplete awareness of the addition of carboplatin to the HEC category and/or physician beliefs that triple antiemesis prophylaxis is not required for this agent. Beyond carboplatin, past research indicates considerable gaps in antiemetic prophylaxis even for cisplatin, which is universally recognized as HEC.

The researchers cited several possible reasons for these gaps:

  • Subordination of physician attention to supportive care relative to therapeutic intervention
  • Physicians neither seeking nor receiving reports of actual CINV symptoms from patients
  • Clinical inertia

In some cases, the above factors may be exacerbated by cost pressure to avoid use of NK1 agents, omission of which was the predominant factor in non-adherence, according to the NCCN researchers.

To resolve this shortcoming in care, and to reduce avoidable acute care use in patients with cancer, the researchers recommended the following actions:

  • Ensure oncologist involvement in institutional or practice formulary committees deciding on chemotherapy “order sets,” which determine the associated antiemetic prophylaxis and other supportive care medications within electronic order systems
  • Assign a “champion” within each practice or institution to lead regular reviews of antiemetic guidelines, ensure order sets follow updated antiemetic guideline recommendations, and actively measure and manage physician adherence. (There is no evidence supporting a “watch and wait” approach to prophylaxis)
  • Continue to increase awareness regarding the increasing role of oncology outcome measures (such as CMS’ OP-35) and their association with future reimbursement
  • Consider the use of the most advanced and recently studied antiemetic prophylaxis agents and evaluate the economics in terms of “total cost of care” and quality of outcomes, without regard for impact on the pharmacy budget relative to the medical budget
  • Develop strategies to monitor patients’ common chemotherapy-induced symptoms between chemotherapy visits and take action as warranted; this has been shown to improve overall survival2

In Closing

The cost of a CINV hospitalization has been estimated at over $14,000,9 based largely on 4 to 5 days of typical duration. Optimizing antiemesis compliance rates and utilizing prophylaxis agents with high rates of CINV protection represent simple yet impactful steps that cancer centers can take to improve care, reduce costs, and potentially avoid acute care use and the consequent reduced ranking on the OP-35 outcomes measure, with its negative consequences for reimbursement.

An old saying states: “The stone that the builders rejected has become the chief cornerstone.” As oncologists focus on the latest treatments in an increasingly complex cancer care environment, it may make sense to also re-focus on one of the basic yet widespread interventions – CINV prophylaxis – as a way to make a broad and meaningful impact on the cost and quality of cancer care in their individual practices.

About the Author

Gary Binder is Senior Director, HEOR & Value-Based Medicine at Helsinn Therapeutics US, Inc. His experience has focused on generating and communicating value-based evidence, tools, and platforms in oncology and other therapy areas. He can be contacted at gary.binder@helsinn.com.


  1. Pyenson BS, Fitch KV, Pelizzari PM. Cost Drivers of Cancer Care: A Retrospective Analysis of Medicare and Commercially Insured Population Claim Data 2004-2014. Milliman, Inc. 2016. http://www.milliman.com/insight/2016/Cost-drivers-of-cancer-care-A-retrospective-analysis-of-Medicare-and-commercially-insured-population-claim-data-2004-2014/. Accessed February 5, 2019.
  2. Basch E, et al. Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment Symptom Monitoring with Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial, JAMA, June 4, 2017.
  3. Centers for Medicare & Medicaid Services, 2017 Measure Refinements Report for Dry Run: Admissions and Emergency Department (ED) – Visits for Patients Receiving Outpatient Chemotherapy. July 2017.
  4. ASCO, Top 5 Advances in 50 Years of Modern Oncology, accessed 2/12/19 at https://www.asco.org/research-progress/cancer-progress-timeline.
  5. Roeland E, et al, Avoidable Acute Care Use Associated with Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin, Fig 1, presented at the NCCN Annual Conference, March 2019.
  6. NCCN Antiemetic Guidelines, 2019.
  7. Roeland E, et al, op.cit.
  8. Roeland, E, et al., What the HEC? Physician variation and attainable adherence targets in antiemetic prophylaxis, presented at the Palliative and Supportive Care in Cancer Symposium, November 2018.
  9. Roeland, E, et al. Inpatient Hospitalization Costs Associated with Nausea and Vomiting Among Patients with Cancer, presented at Palliative and Supportive Care in Cancer Symposium, November 2018.



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