SNMMI 2023: Re-SPECT: Patient Outcomes Following a Response Biomarker Guided Approach to Treatment Using 177Lu-PSMA-I&T in Men with mCRPC

(UroToday.com) The 2023 SNMMI annual meeting included a prostate cancer session, featuring a presentation by Dr. Andrew Nguyen discussing Re-SPECT, a study assessing patient outcomes following a response biomarker guided approach to treatment using ¹⁷⁷Lu-PSMA-I&T in men with metastatic castrate resistant prostate cancer (mCRPC). ¹⁷⁷LuPSMA is an effective treatment in mCRPC with trials, such as VISION and TheraP, adopting a standardized dose interval.^1,2

However, adjusting treatment intervals utilizing early response biomarkers may improve patient outcomes. Early PSA response has been associated with better overall survival, and patients with a >=20% increase in volume + the appearance of new lesions at 12 weeks (RECIP criteria) have worse survival (8.3 months vs 13 months). As such, this study evaluated progression-free survival and overall survival based on treatment interval adjustment utilizing ¹⁷⁷LuPSMA 24-hour SPECT/CT (¹⁷⁷Lu-SPECT) and early PSA response.

This was a retrospective study (May 2019 to April 2022) of 125 men treated on a clinical program with 6-weekly ¹⁷⁷LuPSMA-I&T (median 3 cycles, IQR 2-4) doses, with a median dose 8.0 GBq (95%CI 7.5-8.0). Inclusion criteria included progression on at least one line of androgen receptor signaling inhibition, either failed or were eligible for taxane chemotherapy, ECOG 0-2, eGFR >30 ml/min, hemoglobin > 70 g/L, and platelets > 70,000. Imaging screening involved ⁶⁸GaPSMA-11 PET/diagnostic CT, requiring the following:

SUVmax >= 15 on PSMA PET at >= 1 site
SUVmax >=10 at all measurable sites
No sites of PSMA negative soft tissue metastatic disease on diagnostic CT

¹⁷⁷Lu-SPECT/diagnostic CT were acquired following each therapy, and clinical assessments three times weekly. Following dose 2 (week-6), a composite of PSA and ¹⁷⁷Lu SPECT/CT response (partial response, stable disease and progressive disease) determined ongoing management:

Response group 1 (marked reduction in in PSA/imaging partial response): cease treatment until subsequent PSA rise, then re-treatment
Response group 2 (stable or reduced PSA and/or imaging stable disease): 6 weekly treatment until 6 doses or no longer clinically benefitting
Response group 3 (rise in PSA and/or imaging progressive disease): recommend change to an alternative treatment

Imaging response criteria were as follows:

Image response

Among the 125 men included in the study, the median age was 75 years with the full baseline characteristics as follows:

characteristics

Overall PSA50% response rate was 60% (75/125), median PSA-progression-free survival was 6.1 months (95% CI 5.5-6.7) and median overall survival was 16.8 months (95% CI 13.5-20.1). Stratified by response group, 35% (41/116) were classified as response group 1, 34% (39/116) response group 2, and 31% (36/115) response group 3. PSA50% response rate by response group were 93% (38/41) for response group 1, 74% (29/39) for response group 2, and 8% (3/36) for response group 3. The median PSA-progression-free survival for response group 1 was 12.1 months (95% CI 9.3-17.4), 6.1 months (95% CI 5.8-9.0) for response group 2, and 2.6 months (95% CI 1.6-3.1) for response group 3:

progression response

Overall survival was 19.2 months (95% CI 16.8-20.7) for response group 1, 13.2 months (95% CI 12-18.8) for response group 2, and 11.2 months (95% CI 8.7-15.6) for response group 3:

overall survival

The median months of 'treatment holiday' for response group 1 was 6.1 months (IQR 3.4-8.7). Additionally, 9 men received prior ¹⁷⁷Lu PSMA-617 and were retreated with ¹⁷⁷Lu PSMA I&T with a PSA50% response rate of 56% on re-treatment. There were several limitations of this study, including the retrospective design, some patients in response group 1 after a treatment holiday electing not to have more treatments, and the definition of visual disease response on SPECT not being well defined in >30% of patients.

Dr. Nguyen concluded his presentation discussing Re-SPECT with the following take home messages:

Personalizing dosing intervals using early response biomarkers with ¹⁷⁷LuPSMA has the potential to achieve similar overall treatment responses to that published for continuous dosing, while allowing treatment holidays in responders and early cross-over to potentially more effective therapies in non-responders
Further evaluation in prospective trials is warranted

Presented by: Andrew Nguyen, St. Vincent's Hospital, Sydney, Australia

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, Chicago, IL, Sat, June 24 – Tues, June 27, 2023.

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