(P 413) SUSTAINED EFFICACY DURING DRUG HOLIDAY ON ATEZOLIZUMAB IN PATIENTS WITH ALVEOLAR SOFT PART SARCOMA (ASPS)

Objective: Alveolar soft part sarcoma (ASPS) is a rare disease but more frequent in young adult patients (pts). FDA approved atezolizumab (Atezo) for pediatric and adult pts with metastatic ASPS based on the results of this phase 2 trial of single-agent Atezo (NCT03141684). [1] Pts who remained on single agent treatment for >2 years were given the option of going on a drug holiday (DH) for up to 2 years. We are reporting the response and toxicity data on pts who elected to take an Atezo DH.

Methods: In this ongoing phase 2 study, adult pts are administered intravenous Atezo at a fixed dose of 1200 mg. Atezo is given on Day 1 of each 21-day cycle. Only pts on monotherapy Atezo for >2 years have the option to go on DH. Primary objective is to assess objective response rate (ORR) for Atezo using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with the same response criteria being used to assess response during DH. Secondary objectives include assessment of duration of response and progression free survival (PFS). During a DH, imaging scans are required every 3 months for those who have not had progressive disease (PD). Upon progression, pts are to resume Atezo within 21 days of the scan, with new baseline imaging and reevaluation of eligibility, or go off-treatment. The treating physician, together with the Principal Investigator, may decide to end the DH early (before 2 years) and re-initiate treatment documenting the rationale. Pts reaching the end of a 2-year DH whose disease did not progress are formally taken off treatment and are ineligible to resume that treatment on this study. These pts are followed for response evaluation and follow up every 6 months (± 1 month) until PD, death, patient withdrawal, or enrollment in another protocol, whichever comes first. AEs are documented based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and survival is calculated using the Kaplan-Meier method.

Results: A total of 11 pts have gone on to DH (out of 51 adult pts enrolled) as of 6/10/2024 data cutoff. Among them, 7 (64%) are female, 6 (55%) are white, with a median age of 40 years (range 21-70). Seven patients (64%) had 0 prior lines of treatment (range 0-3), and all pts had ECOG 0-1 (Table 1). Two pts had complete response (CR) and 9 had partial response (PR) as their best response at the time of initiation of DH. On DH, 4 pts completed the study (2-year DH without progression), 1 patient came off due to pt’s choice, and 1 was lost to follow up. Two pts had PD develop during the DH; one of those individuals progressed from PR to PD after 24.4 months of DH and the other patient had CR as best response but developed PD in a non-target lesion (which was later resected) after 3.6 months of holiday. Neither patient reinitiated treatment. Three patients remain on DH.
Except for the two patients noted to have PD, the best response on most recent imaging is identical to best response at the time when pts started the DH (8 pts with PR and 1 patient with CR).
Mean duration since stopping treatment is 19.1 months (range 3.6 to 25.3 months) (Figure 1). Grade 2 or above treatment-related AEs (TRAE) that occurred in these 11 patients when the DHs began included one instance each of grade 2 pruritus, iron deficiency anemia, adrenal insufficiency, hot flashes, and anxiety. In addition, there was one instance of grade 3 glucose intolerance during treatment. Among these toxicities, pruritus, iron deficiency anemia, and adrenal insufficiency have resolved. No TRAEs occurred during DH (Table 2).

Conclusion: The efficacy of Atezo in ASPS continued despite holding treatment for up to 2 years. Two patients had PD on DH but were not reinitiated on atezo. As Atezo is approved in the United States for treatment of ASPS, real-world data are anticipated that will answer questions of response to retreatment.