Pembrolizumab efficacy durable for long-term management of bladder cancer
Long-term data from the KEYNOTE-045 trial showed ongoing superiority of the programmed death 1 (PD-1) inhibitor pembrolizumab compared with chemotherapy for advanced and metastatic bladder cancer, according to results presented at the ASCO Genitourinary Cancers Symposium 2018 (ASCO GU 2018).
After a median follow-up of 27.7 months, overall survival (OS) was still significantly longer among patients randomized to receive pembrolizumab (n=270) vs chemotherapy (n=272) (median, 10.3 months vs 7.3 months; hazard ratio [HR], 0.70; p<0.0002). [ASCO GU 2018, abstract 410]
Objective response rate (ORR) was also shown to be higher (21.1 percent vs 11 percent), with a longer median duration of response (not reached vs 4.4 months), among patients treated with pembrolizumab vs chemotherapy.
Moreover, a greater proportion of responses lasted for more than 12 months in patients who received pembrolizumab vs chemotherapy (68 percent vs 35 percent).
The OS benefit with pembrolizumab vs chemotherapy was also seen in all programmed death ligand-1 (PD-L1) expression subgroups (HR: combined positive score [CPS] <1, 0.82; CPS ≥1, 0.58; CPS <10, 0.75; CPS ≥10, 0.56).
Responses to pembrolizumab were maintained regardless of age, Eastern Cooperative Oncology Group performance status (ECOG PS), prior therapy, liver metastases, baseline haemoglobin, time from last chemotherapy, histology, risk factor group, and choice of chemotherapeutic agents.
In terms of toxicity profile, lower rates of adverse events (AE) were seen with pembrolizumab vs chemotherapy (any grade, 62 percent vs 90.6 percent; grade ≥3, 16.5 percent vs 50.2 percent).
“After 2 years of follow-up, more patients in the pembrolizumab arm were still alive as compared with the chemotherapy arm [27 percent vs 14.3 percent]. This survival rate is similar to what has been seen with other immune-sensitive cancers such as melanoma,” primary investigator Professor Joaquim Bellmunt of the Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, US, pointed out.
“The results are exciting because they are the most mature data we have so far in the modern era of immunotherapy,” commented discussant Professor Robert Jones of the University of Glasgow and Beatson West of Scotland Cancer Centre, UK.
“This is a step forward and a breakthrough news for our patients, although this benefit is seen in only around 20 percent of patients. The field is now moving towards combination therapies and searching for predictive biomarkers to identify patients who will benefit the most from these new treatments,” added Bellmunt.
“There are four currently ongoing trials testing immunotherapy in combination or compared with chemotherapy in the first-line setting. Hopefully, we can improve the outcome beyond 20 percent in our patients with bladder cancer,” said Bellmunt.
Interim analysis of the KEYNOTE-045 trial demonstrated that pembrolizumab was associated with significantly longer OS (median, 10.3 months vs 7.4 months; HR, 0.73; p=0.002) and a lower rate of AEs (any grade, 60.9 percent vs 90.2 percent; grade ≥3, 15 percent vs 49.4 percent) vs chemotherapy as second-line treatment for advanced urothelial carcinoma. [N Engl J Med 2017;376:1015-1026]