Balance needed for short- vs long-term immunotherapy risks, benefits in mUC
medwireNews: Patients with cisplatin-ineligible metastatic urothelial carcinoma (mUC) have decreased short-term overall survival (OS) when receiving immunotherapy versus carboplatin-based chemotherapy in the first line, but increased long-term survival, study findings indicate.
Therefore, “clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy,” write Emily Feld (University of Pennsylvania, Philadelphia, USA) and co-authors in European Urology.
Feld and team retrospectively reviewed the electronic health records of 2017 US patients (median age 78 years, 73% men) with cisplatin-ineligible mUC receiving first-line carboplatin-based chemotherapy (n=1530) or immunotherapy (single-agent nivolumab, pembrolizumab, atezolizumab, durvalumab, or avelumab; n=487) between 2011 and 2018.
Using inverse probability of treatment weighting (IPTW) to adjust for confounding by factors associated with treatment selection, the researchers found that median OS was 9 months with immunotherapy and 11 months with chemotherapy.
At 12 months, patients in the immunotherapy group had a significant 37% increased likelihood for death relative to those in the chemotherapy group, with IPTW-adjusted OS rates of 39.6% versus 46.1%.
However, among the patients who survived the first 12 months, there was a significant 50% lower risk for death beyond this point with immunotherapy than with chemotherapy. At 36 months, the IPTW-adjusted OS rates were 28.3% and 13.3%, respectively.
The researchers comment that their “observation of decreased short-term survival with immunotherapy is consistent with the preliminary results from data monitoring committees’ early review of two ongoing first-line immunotherapy trials” and may represent a subgroup of patients who either do not respond to immunotherapy or who have hyperprogression.
“Therefore, some populations (eg, those with symptomatic or high-volume disease) may instead benefit from chemotherapy as initial therapy,” they write.
In exploratory analyses the team found that, at 6 months, survival was highest for PD-L1-positive patients and lowest for PD-L1-negative patients treated with immunotherapy versus chemotherapy.
This supports “the EMA and FDA label revision restricting immunotherapy use to mUC patients whose tumors are PD-L1 positive (approximately 30% of all tumors),” the researchers remark.
Feld et al conclude that their “findings of improved short-term survival with carboplatin-based chemotherapy but superior long-term survival with immunotherapy provide a rationale for considering first-line combination of chemotherapy and immunotherapy in an effort to achieve maximal survival for all patients.”
“This is currently being explored in the ongoing trials KEYNOTE-361 and IMVigor-130.”
By Laura Cowen
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