SGO, FWC, GOG-F* Communique: Considerations When Treating Patients with Gynecologic Cancers on Clinical Trials in the Setting of Chemotherapy Shortages

1. Whether a patient is treated on a clinical trial or is receiving standard-of-care therapy, cisplatin and carboplatin should be prioritized for patients receiving treatment for curative intent or when prolonged clinical benefit is anticipated.
2. Patients receiving platinum-based regimens as either standard-of-care or on clinical trial should be given equal prioritization during the drug shortage.
3. For institutions anticipating a prolonged platinum drug shortage, consider discussion with oncology colleagues at institutions without similar chemotherapy drug shortages regarding potential new patient trial referrals.
4. For platinum-based investigator-initiated trials or cooperative group studies in which referral to another institution is not feasible, avoid enrollment of new study participants until confirmation of an adequate and sustainable institutional drug supply. Investigators should communicate with their local IRBs and with the study chairs/principal investigators if a pause in enrollment is anticipated.
5. In settings in which an institutional drug shortage develops when patients are already enrolled on a platinum-based clinical trial, the respective study chairs/principal investigators should be contacted to discuss each situation on a case-by-case basis.
   1. Although drug shortages are known to lead to protocol deviation in clinical trials and may impact data interpretation, patient safety and outcomes must be prioritized^[3]. Additionally, based on upon the Department of Health and Human Services (HHS) regulations 45 CFR 46.103(b)(4)(iii), which provide robust protections for human research study subjects, it is reasonable to consider modifications to trials in the setting of commercial drug shortages^[4]. Modifications to consider for patients enrolled on platinum-based trials include:
      1. Utilizing the lowest effective dose of platinum (i.e., carboplatin AUC 4-5 IV or cisplatin 50-75 mg/m2 IV every 21 days)
      2. Substituting cisplatin for carboplatin or carboplatin for cisplatin at institutions in which these drug shortages do not overlap.
      3. Delaying the next chemotherapy cycle briefly if drug supply is anticipated soon.
      4. Omitting the platinum-based therapy but continuing with other study treatment if receiving a multi-drug regimen.
6. When a drug shortage exists, patients enrolled on clinical trials must be informed of any treatment delays or modifications, as well as potential associated risks^[4]. Any treatment modifications and associated patient counseling should also be documented in the patient’s medical record and reported to the institutional IRB.
7. The following NRG trials currently utilize a platinum regimen either as a primary regimen or drug substitution^[5]:
   1. Cisplatin
      1. NRG-GY019
      2. NRG-GY024
   2. Carboplatin
      1. NRG-GY018
      2. NRG-GY019
      3. NRG-GY022
      4. NRG-GY026
      5. NRG-GY027
8. The following GOG-F trials currently utilize a platinum regimen either as a primary regimen or drug substitution^[6]:
   1. Cisplatin
      1. GOG 3053 (KEYNOTE B51)
      2. GOG 3064 (KEYNOTE C93)
      3. GOG 3068 (HOTT)
   2. Carboplatin
      1. GOG 3025 (DUO-O)
      2. GOG 3031 (RUBY)
      3. GOG 3035 (FLORA 5)
      4. GOG 3036 (KEYLYNK 001)
      5. GOG 3053 (KEYNOTE B51)
      6. GOG 3064 (KEYNOTE C93)
      7. GOG-3076 (On Prime)
9. The SGO, FWC, and GOG-F continue to monitor the supply shortage closely. This document is subject to an update as more information is learned.
   

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

The SGO, FWC, and GOG-F wish to acknowledge the following members and professionals for their contributions to this communique: Amanda Fader, MD; Leslie Randall, MD; Thomas Herzog, MD; Bhavana Pothuri, MD, MS; David O’Malley, MD; Angeles Alvarez Secord, MD, MHSc; Roisin O’Cearbhaill, MD; Peter Rose, MD; Deborah Armstrong; MD; Paul DiSilvestro, MD; Eloise Chapman-Davis, MD; Ginger Gardner, MD; Navya Nair, MD, MPH; Ms. Katherine Campbell; 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.

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