Pembro/chemo combo shows promise in small cell/neuroendocrine bladder and prostate cancer

Treatment with pembrolizumab (Keytruda) plus cisplatin-based chemotherapy was found to be safe and tolerable in patients with small cell bladder cancer and small cell/neuroendocrine prostate cancer, according to data from a phase 1b trial (NCT03582475) published in Cell Reports Medicine.¹

Arnold I. Chin, MD, PhD

“The combination of pembrolizumab and chemotherapy presents a promising new treatment approach for these challenging-to-treat, rare cancers and could be a major breakthrough for patient care,” said senior author Arnold I. Chin, MD, PhD, in a news release on the findings.² Chin is professor of urology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

In total, the study enrolled 15 adult patients through UCLA.³ Of these, 7 patients had advanced or metastatic small cell bladder cancer (cohort 1), and 8 patients had primary small cell or neuroendocrine prostate cancer (cohort 2).

The overall response rate (ORR) among all patients and within each cohort was 43% (95% CI, 0.06-0.080).

At 12 months, overall progression-free survival (PFS) was 64% (95% CI, 0.44-0.95). Specifically, PFS was 86% (95% CI, 0.63-1.00) in cohort 1 and 43% (95% CI, 0.18-1.00) in cohort 2. At 24-month follow-up, PFS was 50% (95% CI, 0.30-0.84) overall. Stratified by cohort, PFS was 86% (95% CI, 0.63-1.00) in cohort 1 and 14% (95% CI, 0.2-0.88) in cohort 2.

Similarly, at 12 months, overall survival (OS) was79% (95% CI, 0.60-1.00) across both cohorts. Within each cohort, OS was86% (95% CI, 0.63-1.00) in cohort 1 and71% (95% CI: 0.45, 1.00) in cohort 2. At the 24-month time point, OS was 71% (95% CI, 0.51-1.00) across both cohorts. OS was86% (95% CI: 0.63, 1.00) in cohort 1 and 57% (95% CI, 0.30-1.00) in cohort 2.

The median PFS and OS were not reached in cohort 1 at the time of data report. In cohort 2, the median PFS was 7 months, and the median OS was 27 months. According to the authors, the historical median OS for small cell bladder cancer is approximately 7 to 13 months, and 7 to 9 months for small/cell neuroendocrine prostate cancer.

Chin noted, “These results suggests that the combination therapy could provide a substantial survival benefit [to these patients].”²

The authors also explained, “Although our [small cell bladder cancer] cohort 1 had more favorable results then our prostate cohort 2, there may be many reasons for this disparity.” For starters, they note, “In cohort 1, 71% were AJCC stage III and 29% stage IV compared to all stage IV in cohort 2.”

The investigators also observed that clonal expansion of diverse T cell repertoire correlated with improved progression-free survival.

Regarding safety, treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 40% of patients overall, consisting of 57% (n = 4) of patients in cohort 1 and 25% (n = 2) of patients in cohort 2.

According to the authors, “The most common treatment-related adverse events were weakness and fatigue, skin-related diseases including rash or pruritus, diarrhea, peripheral neuropathy, and hypothyroidism.”

No grade 5 events were reported, and no patients discontinued treatment due to toxicity.

The authors suggest that larger clinical trials are needed to confirm these findings.

References

1. Gu Y, Ly A, Rodriguez S, et al. PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers. Cell Rep Med. 2024;5(11):101824. doi:10.1016/j.xcrm.2024.101824

2. Combination approach shows promise for treating rare, aggressive cancers. News release. University of California – Los Angeles Health Sciences. November 12, 2024. Accessed December 2, 2024. https://www.eurekalert.org/news-releases/1064057

3. Pembrolizumab with combination chemotherapy in treating participants with locally advanced or metastatic small cell/​neuroendocrine cancers of urothelium or prostate. ClinicalTrials.gov. Last updated September 19, 2024. Accessed December 2, 2024. https://clinicaltrials.gov/study/NCT03582475