LuPSMA ‘promising alternative’ to cabazitaxel in mCRPC
medwireNews: The radiolabeled small molecule lutetium-177-prostate-specific membrane antigen-617 (LuPSMA) offers higher activity and better patient-reported outcomes (PROs) than cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC), research shows.
Writing in The Lancet, Michael Hofman (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) and co-authors say that data from the phase 2 TheraP trial, along with results from other trials, “provide compelling evidence that [LuPSMA] is an active treatment for men with castration-resistant prostate cancer who have progressed after docetaxel chemotherapy and androgen receptor-directed therapy.”
The study, conducted at 11 centers in Australia, included 200 men with prostate-specific membrane antigen (PSMA)-positive mCRPC who were randomly assigned to receive LuPSMA (6.0–8.5 GBq every 6 weeks for up to six cycles; n=99) or cabazitaxel (20 mg/m2 every 3 weeks for up to 10 cycles; n=101).
After a median 18.4 months of follow-up, the primary outcome of prostate-specific antigen (PSA) response rate (≥50% reduction from baseline) in the intention-to-treat population was significantly higher with LuPSMA than with cabazitaxel, at 66% versus 37%. The difference remained significant when the data were analyzed by treatment received, at 66% versus 44%.
At the same time as The Lancet publication, Hofman presented the secondary findings at the 2021 Genitourinary Cancers Symposium.
The researchers found that the 1-year progression-free survival (PFS) rate was significantly better in the LuPSMA arm than in the cabazitaxel arm, at 19% and 3%, respectively, and a hazard ratio (HR) of 0.63. Similar results were observed for radiographic and PSA PFS, with corresponding HRs of 0.64 and 0.60.
However, Hofman noted that median PFS was 5.1 months in both arms, which he said demonstrates that “the treatment effect was not constant with respect to time, with greater benefit emerging after 6 months.”
The investigators also looked at PROs using the EORTC QLQ-C30 tool. They found that, at the end of the follow-up period, global health status was similar with LuPSMA and cabazitaxel, at mean scores of 64 and 60 points, respectively.
However individuals in the LuPSMA arm reported, on average, significantly better outcomes for the fatigue (34 vs 40 points), social functioning (79 vs 73 points), insomnia (24 vs 29 points), and diarrhea (9 vs 16 points) domains.
Compared with cabazitaxel, LuPSMA was also associated with significantly lower rates of specific troublesome symptoms such as altered taste (54 vs 69%), dizziness (38 vs 53%), urinary symptoms (38 vs 62%), sore hands and/or feet (35 vs 43%), skin rash (14 vs 32%), and hair loss (10 vs 42%). And the authors point out that there were no PRO domains that had a superior outcome with cabazitaxel.
In terms of safety, grade 3 or 4 adverse events were similar to those previously reported for the treatments in question and occurred at rates of 33% and 53% in the LuPSMA and cabazitaxel groups, respectively.
Hofman concluded: “Lutetium-PSMA-617 represents a new class of effective therapy for men with metastatic castration-resistant prostate cancer.”
But he also cautioned that the findings “might not be applicable to men selected less carefully.”
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