July 2019 Edition Vol.11, Issue 7

Drug Costs: Putting Oncologists in the Driver’s Seat

By Christina Bennett, MS

The cost of cancer care—particularly new innovative high-cost drugs—is a growing concern for patients, and while oncologists do not control the launch price of drugs, they do decide how drugs are used and are responsible for their proper utilization.1 With this is mind, several studies at the 2019 American Society of Clinical Oncology (ASCO) annual meeting proposed avenues for reining in costs without compromising the quality of care.

Dosing Overhaul for Pembrolizumab and Nivolumab

An analysis of cancer patients receiving the checkpoint inhibitors, pembrolizumab or nivolumab, revealed that if these high-priced medications were dosed by a patient’s weight and providers participated in vial-sharing practices, the collective cost-savings each year could potentially reach $1 billion worldwide.2 Vial sharing is the practice of using residual medicine from one patient to treat a subsequent patient on the same day.

“Pembrolizumab and nivolumab are a major source of cancer drug spending,” said study presenter Evan Hall, MD, MPhil, Stanford School of Medicine.

In 2018, the two drugs exceeded an estimated $14 billion of combined sales worldwide, and it was recently reported that an estimated 43.6% of cancer patients in the United States are eligible for checkpoint inhibitor therapy.3,4

“The potential market for these drugs is increasing all the time,” said Dr. Hall.

There is evidence that fixed-dosing of pembrolizumab and nivolumab increases spending, compared to weight-based dosing, even though weight-based dosing alone can result in significant drug wastage—to the tune of more than $1.8 billion each year.5 Vial sharing could minimize wastage. However, vial sharing is not a common practice in the United States, and one reason for this may be the lack of incentive: The Centers for Medicare & Medicaid Services reimburses for any unused drug left in the vial.

Given this, Dr. Hall and colleagues proposed a dose minimization scheme that incorporated both weight-based dosing and vial sharing. Using data from 271 patients who received 1,029 doses of pembrolizumab or nivolumab during a four-month period at three Stanford sites, the researchers calculated the potential cost-savings if the dose minimization scheme had been implemented.

For pembrolizumab, dosing by weight without vial sharing had little impact—spending was reduced by only $0.05 million (–0.7%). When vial sharing was included, the savings ballooned to $1.11 million (–17.3%). In contrast with nivolumab, a similar reduction in spending of about $0.30 million (–9%), was predicted regardless of vial sharing.

The difference in impact of vial sharing on drug spending can be attributed to pembrolizumab being available in the United States only as a 100-mg vial, whereas nivolumab is available in three vial sizes (40-, 100-, and 240-mg), thus minimizing the opportunity for drug wastage.

“The success of implementation of this strategy will depend on multiple things, primarily, on payer contracts,” said study discussant Kerin Adelson, MD, Chief Quality Officer, Yale University, noting that if practices were to give lower doses, they may miss out on revenue. She stressed, “The oncology reimbursement model must shift to reward many of the unreimbursed services that we provide our patients and decrease practice dependence on drug revenue.”

In a similar study reported at ASCO, researchers investigated another aspect of checkpoint inhibitors that could cut costs: dosing frequency.6

“The current FDA-recommended dosing likely gives way more drug exposure than is necessary to be effective,” said lead study author Cody Peer, PhD, Clinical Pharmacology Program, National Cancer Institute.

Using a literature-based simulation model, Dr. Peer and colleagues demonstrated that nivolumab (currently dosed at 240 mg every 2 weeks or 480 mg every 4 weeks) could be dosed at 480 mg every 8 weeks after the first 2 doses. Specifically, they found that dosing every 8 weeks maintained effective concentrations in nearly 90% of patients. Currently, treatment with nivolumab costs a single patient more than $150,000 annually, but if the drug were dosed every 8 weeks, the cost could be cut in half.

Although this study alone will not change dosing paradigms, the FDA does take simulation modeling “seriously,” said Dr. Peer. “It’s not just an academic exercise to them.” For instance, the FDA’s decision to allow patients to receive nivolumab 480 mg every 4 weeks was based on simulation modeling alone.

A clinical trial to confirm these findings is in the very early stages. Dr. Peer said a protocol of the trial is being written and he’s gathering support from as many clinical sites as he can around the country and internationally. “[Funding] has yet to be ultimately decided, but we’re keeping our options open,” he said.

Remember the Guidelines

A study evaluating the real-world prescribing patterns of granulocyte colony stimulating factor (GCSF) showed that physician prescribing patterns can significantly impact healthcare spending.7

At a single health network, two prescribing patterns were retrospectively identified for prostate cancer patients receiving docetaxel. The first pattern identified was prophylactic administration of pegfilgrastim, typically on day 2 of the chemotherapy cycle. The second pattern was as-needed administration of filgrastim, as determined by nadir check on day 8 of the chemotherapy cycle; patients who were neutropenic were then eligible for filgrastim.

A cost analysis of the two prescribing patterns revealed that the average per-cycle cost of as-needed filgrastim for each patient was about $600, whereas the cost of prophylactic pegfilgrastim was about $7,300—a greater than 10-fold difference. The total cost of treatment in the study for patients who received as-needed filgrastim was about $120,000, whereas the total cost of treatment for patients who received prophylactic pegfilgrastim was about $1.1 million.

However, neither of the prescribing patterns are supported by ASCO guidelines. Dr. Adelson stated the actual difference in growth factor costs between the two groups would be even greater if the as-needed approach was guideline adherent and limited to patients who developed fever.

“Furthermore,” she said, “the cost in both groups would be lower if the doctors just followed the guidelines.”

Making “Super-utilizers” Less Super

Identifying high-risk patients—or “super-utilizers”—and intervening with a twice weekly phone call successfully reduced hospital admissions and cut costs for the multi-specialty group practice Crystal Run Healthcare, a participant of the Oncology Care Model (OCM).8

The strategy involved nurse practitioners performing a risk stratification assessment of each patient during their initial orientation visit. Patients who were deemed potential super-utilizers were called twice weekly between 8 am and 10 am.

“It’s the quietest time of the day, patients are likely to still be at home, and it’s early enough in the day that options still exists,” said study presenter Manuel Perry, MD, Crystal Run Healthcare.

Over the course of one year, hospital admissions dropped from 21.3 to 18.7 per 100 Medicare beneficiaries (12.2%). Cost per Medicare beneficiary per month also dropped from $979 to $885 (9.6%). The annual cost reduction totaled to approximately $600,000 for the practice’s cohort of 600 OCM patients. In addition, patient satisfaction scores improved.

“Although we have had great success, there have been some challenges,” said Dr. Perry. For instance by using nurse practitioners, the intervention was costly and time intensive. In addition, the practice continued to have patients who required admission to the hospital but were not identified as high risk. Lastly, he said, “Our most recent OCM feedback report showed an increase of 0.8 admissions for 100 beneficiaries, which may suggest that we have achieved a plateau in the benefits of our intervention.”

Dr. Adelson applauded the study but highlighted a particular challenge with care management strategies: “Outside of OCM, no care management services are actually reimbursed.”

   Drug Prices Take Center Stage at ASCO Town Hall

This year, the ASCO Town Hall was dedicated solely to the issue of drug pricing and featured a discussion with Rodney Whitlock, PhD, McDermott+Consulting, that was moderated by Jeffery Ward, MD, Swedish Cancer Institute Medical Oncology – Edmonds. Dr. Whitlock offered insights across a swath of policy changes in the pipeline.

When asked whether the politics could change about the US government setting drug prices, Dr. Whitlock said the government has a “renewed interest” and “openness” to set drug prices. Congress is under pressure to pass legislation that would stop surprise medical bills. Surprise billing “at its core” allows certain providers to set a price and get that price, and if prices can be controlled there, “it’s a gateway drug to larger price controls,” Dr. Whitlock said.

Last fall, the International Price Index model was put forth as a way to lower Medicare Part B drug prices by more closely aligning with other countries’ prices, but the anticipated proposed rule was not announced in the spring. Dr. Whitlock speculated that this policy, and several others in the drug pricing space, sit as bargaining chips in what may come together as a larger deal in the fall.

In early May, a rule was finalized that will require drug manufacturers to include their list prices in direct-to-consumer television advertisements for certain drugs covered by Medicare or Medicaid.

“What you’re going to end up seeing is one hell of a fight in the courts involving first amendment lawyers as to whether or not commercial speech is protected as free speech,” Dr. Whitlock said when asked about this potential change.

“Current proposals seem to have potential for chaos,” said Dr. Ward. “Is there a cautious way forward?”

To this, Dr. Whitlock replied, “A lot of the things you see moving through Congress right now are what I would describe as baby steps. There’s no click-your-heels-together-three-times solution to drug pricing that makes it all better.”

“What we’ll be seeing is how much are members of Congress able to make the case that they’re trying to do things that make a difference without being able to delivery very quickly, because it doesn’t happen quickly,” said Dr. Whitlock.

Editor’s Note:  As OBR went to press, several actions took place that changed the status of some drug policy initiatives mentioned above.  The Senate committee voted in favor of moving its surprise billing proposal forward to the Senate floor. A federal judge struck down the rule that would have required the inclusion of drug list prices in direct-to-consumer television advertisements the day before it was scheduled to take effect. (Although not included above, the rule that would have banned after-the-point-of-sale rebates was also abandoned.)

The International Pricing Index proposal is still being pursued by the administration. 


  1. American Society of Clinical Oncology. American Society of Clinical Oncology position statement on addressing the affordability of cancer drugs. J Oncol Pract. 2018;14(3):187-192.
  2. Hall ET, Zhang J, Kim E-J, et al. Economic analysis of alternative pembrolizumab and nivolumab dosing strategies at an academic cancer center. J Clin Oncol. 2019;37:(suppl; abstr 6504).
  3. Philippidis A. Top 10 best-selling cancer drugs of 2018. https://www.genengnews.com/a-lists/top-10-best-selling-cancer-drugs-of-2018/.  Published online April 22, 2019. Accessed June 12, 2019.
  4. Haslam A and Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open. 2019;2(5):e192535.
  5. Bach PB, Conti RM, Muller RJ, Schnorr GC, and Saltz LB. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016;352:i788.
  6. Peer CJ, Goldstein DA, Ratain MJ, and Figg WD. A modeling and simulation study of less frequent dosing of nivolumab 480 mg. J Clin Oncol. 2019;37:(suppl; abstr 3115).
  7. Barrett C, Park SJ, Gaertner K, and Mao S. The financial impact of physician practice patterns: An analysis of as-needed filgrastim versus prophylactic pegfilgrastim in patients with prostate cancer receiving docetaxel. J Clin Oncol. 2019;37:(suppl; abstr 6506).
  8. Perry M, Rudy-Tomczak K, Lalanne J, et al. A process to reduce hospital admissions in the OCM population through focused intervention of super-utilizers. J Clin Oncol. 2019;37:(suppl; abstr 6505).

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