SGO, FWC and GOG-F* Communique: Considerations When Treating Persons with Gynecologic Cancers in the Setting of Pegylated Liposomal Doxorubicin Shortages

On July 19, 2023, the American Society of Health-System Pharmacists website reported a pegylated (PEG) liposomal doxorubicin injection shortage. A prolonged U.S. shortage of PEG-liposomal doxorubicin first occurred in November 2011 and had largely resolved by 2015. This communication provides guidance for treating patients with gynecologic cancers in the context of limited PEG-liposomal doxorubicin availability.

Hospital systems or similar organizations are encouraged to facilitate open and frequent communication among multi-specialty teams, including gynecologic, medical, and radiation oncologists, pharmacists, infusion managers, advanced practitioners, and patient advocates. In doing so, the goal is to create institution and population-specific strategies to overcome anticipated treatment challenges.

Importantly, cancer care disparities may emerge or worsen in times of resource scarcity. As treatment recommendations are adjusted during this shortage, identifying patients at risk for experiencing structural barriers to care and having a plan to mitigate those barriers must be considered as part of each institution’s strategic plan. Therefore, the allocation of limited-supply drugs must be prioritized in a transparent and data-driven fashion to ensure thoughtful and equitable distribution. Hospital leadership, administrators, pharmacists, and payors must also facilitate considerable operational workflow resources to ensure adequate and equitable patient care.

Further information, including estimated drug resupply dates by manufacturer, is available from the American Society of Health-System Pharmacists website for doxorubicin liposomal injection.

A list of current and resolved drug shortages and discontinuations can be found on the FDA website. Please refer to the SGO rapid communiques dated April 21, 2023 and May 24, 2023, for details and guidance regarding platinum shortage.

General Principles

1. PEG-liposomal doxorubicin (Doxil, pegylated liposomal doxorubicin, Doxorubicin liposomal) is not bioequivalent to doxorubicin (Adriamycin). Do not substitute these drugs on a mg per mg basis.
2. PEG-liposomal doxorubicin does not have the same side-effect profile as doxorubicin. Doxorubicin has a significant risk of cardiotoxicity, requires additional cardiac monitoring, and central venous access is strongly encouraged.
3. PEG-liposomal doxorubicin does not have equal activity to doxorubicin. For the treatment of epithelial ovarian cancer, doxorubicin is a less effective agent.
4. If an alternative agent with comparable efficacy and safety is available, then PEG-liposomal doxorubicin should not be ordered. Refer to the NCCN standard of care guidelines for non-liposomal containing regimens².
5. PEG-liposomal doxorubicin should be prioritized for the treatment of ovarian cancer as well as frailer patients with uterine cancers or sarcomas if not candidates for doxorubicin.
6. To preserve PEG-liposomal doxorubicin at institutions in short supply, consider the following:
   1. For platinum-sensitive ovarian cancer, prioritize non-liposomal doxorubicin-containing regimens such as platinum-doublets with paclitaxel or gemcitabine +/- bevacizumab.
   2. For platinum-resistant ovarian cancer, prioritize non-liposomal doxorubicin-containing regimens such as single-agent paclitaxel, topotecan, or gemcitabine +/- bevacizumab or consider mirvetuximab for FOLR1+ disease.
   3. Preserve PEG-liposomal doxorubicin by rounding doses down to the nearest vial size.
   4. Consider PEG-liposomal doxorubicin 30mg/m2 rather than 40mg/m2 dosing, if appropriate².
   5. When combined with carboplatin, the starting dose for PEG-liposomal doxorubicin is 30mg/m2 on a 28-day cycle (not a 21-day cycle).
7. When unfamiliar with an alternative chemotherapy regimen, consider consultations with your institutional pharmacist and other gynecologic oncology or medical oncology colleagues. Use additional caution when writing and processing orders for chemotherapy drugs, especially when switching between chemotherapy agents.
8. Seek prompt institutional approval and implementation of order sets for alternative treatment regimens.

*Organizations involved in production of this communique include the Society of Gynecologic Oncology, the Foundation for Women’s Cancer, and The GOG Foundation, Inc.

Content is subject to updating as additional information becomes available.

These recommendations are not meant to be a substitute for clinical judgment at the individual patient level, nor should they supersede other policies at the institutional level. All decisions should be made in the context of the unique circumstances where members practice, including other local resource considerations. We encourage members to work closely with their institutions to meet patients’ needs and advocate for transparent allocation of limited drug supply. Sites participating in clinical trials should contact study sponsors (if applicable).

References:

1. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=969
2. Armstrong, D.K., et al., NCCN Guidelines(R) Insights: Ovarian Cancer, Version 3.2022. J Natl Compr Canc Netw, 2022. 20(9): p. 972-980.

The SGO, FWC, and GOG-F wish to acknowledge the following members and professionals for their contributions to this communique: Roisin O’Cearbhaill, MD; Michael Bookman, MD; Amanda Fader, MD; Renata Urban, MD: Brian Slomovitz, MD; Angeles Alvarez Secord, MD; Peter Rose, MD; Thomas Herzog, MD; Ginger Gardner, MD; Ms. Jenna Cummins; Ms. Elizabeth Kix; Ms. Katie Martino; Ms. Kayla Nixon; Ms. Jessica Oldham; Ms. Traci Schwendner.

For questions or further guidance, please email sgo@sgo.org.