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Taken together, a unique approach to introduce PD-1/PD-L1 therapy earlier in the metastatic disease paradigm, without either combination in the 1st line setting or compromising response rate with single agent use, is to create a new disease state. Patients that have received prior platinum therapy for metastatic urothelial carcinoma, who obtain a response or stable disease, are great candidates for maintenance therapy with PD-1/PD-L1 therapy. As a result, this is neither 1st line or 2nd line therapy. Many in the field have informally termed this the “1.5 line” of therapy. In addition to being a unique regulatory niche, this approach is pragmatic. By introducing lower toxicity agents to patients who may be suffering from significant chemotherapy-associated toxicities, patients may preserve quality of life with potentially improved efficacy outcomes. This kind of maintenance or consolidative approach justifies the designation of this new disease state.
In regards to ongoing trials in this space, avelumab is being tested in a phase 3 trial with the goal of improvement in overall survival for patients who do not progress after receipt of 4-6 cycles of prior platinum-based chemotherapy. Patients (n=668) are being randomized between avelumab and best supportive care. Best supportive care is very acceptable in this disease state, as most patients will practically take a chemotherapy break after 4-6 cycles of platinum-based chemotherapy. Meanwhile, the Hoosier Cancer Research Network has a 200 patient randomized phase 2 trial, using 6-month progression-free survival as the primary endpoint. Although this endpoint may not be viewed as noteworthy as overall survival, prolonging progression-free survival with pembrolizumab over placebo in this setting is still clinically meaningful, given the cumulative toxicities of chronic chemotherapy.
In conclusion, creating a new disease state for novel therapeutic testing is pertinent to our goals as clinicians if the endpoints and impact are of importance. In this situation, thoughtful consideration has gone into the development of the above-mentioned trials to ensure that patient needs are being met. Hence, we should wholeheartedly support these efforts by accruing and referring patients for these trials.
Highlighted 1.5 Line Metastatic Urothelial Cancer Trials
- Avelumab – JAVELIN Bladder 100 (NCT02603432)
- Pembrolizumab (NCT02500121)
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