High Overall Survival Rates Observed With Subsequent Platinum-Based Chemotherapy in mUC

Risa Wong, MD

Subsequent platinum-based chemotherapy (sPBC) was associated with higher rates of overall survival (OS) compared with patients who received subsequent non-platinum-based chemotherapy (sNPBC) for the treatment of metastatic urothelial carcinoma (mUC), according to retrospective data presented at the 2021 Genitourinary Cancers Symposium.

The current standard of care for mUC is first-line platinum-based chemotherapy. In later-line settings, the standard therapies used include erdafitinib (Balversa) and enfortumab vedotin (Padcev). For patients who are either ineligible for these agents or who have progressed on them, chemotherapy remains an option. Selecting which chemotherapy regimen to choose, however, remains unclear.

The retrospective study looked at the data on 296 patient with mUC. Of those patients, 135 received sPBC and 161 received sNPBC. Baseline characteristics between the 2 groups were similar. However, more patients in the sPBC group had achieved more stable disease and had higher hemoglobin values. For patients receiving sPBC, the median OS was 7.9 months and 5.5 months for the sNPBC group. Additionally, patients who received sPBC were more likely to achieve stable disease or response than those who received sNPBC (57.4% vs. 44.8%). 

In an interview with Targeted Oncology, Risa Wong, MD, a hematology/oncology fellow at the University of Washington, discussed platinum versus non-platinum containing chemotherapy as a later-line treatment for mUC.

TARGETED ONCOLOGY: Can you start with describing the type of patients who may require subsequent chemotherapy after prior chemotherapy or targeted therapy?

WONG: Patients with metastatic urothelial carcinoma who are fit enough to receive it, get first-line platinum-based combination chemotherapy as standard of care. In the past, after they subsequently progressed, there were very limited options for subsequent therapy, and providers ended up retreating many of these patients with chemotherapy, either rechallenging them with a platinum-based regimen or switching to a non-platinum-based chemotherapy regimen. Fortunately, in the last handful of years, there's been a lot of advances in the treatment of metastatic urothelial carcinoma. So now, immune checkpoint inhibitors, [such as] enfortumab vedotin and erdafitinib, are all options for later line therapy. However, there are still going to be patients who either can't receive those agents or who subsequently progressed despite receiving those therapies. And those are the patients who providers might consider treating again with chemotherapy.

Considering that the best form of chemotherapy is unknown for this patient population, what are outcomes generally like for this patient population?

Unfortunately, regardless of the type of subsequent chemotherapy that was used, median overall survival for the patients in our study was on the order of several months after initiating subsequent chemotherapy and median progression-free survival was only on the order of a few months.

Can you provide background on the retrospective study? What were the study methods?

So, this was a retrospective study using data from the retrospective international study of cancers of the urothelium, which is also known as RISK for short. And it included data from over 3000 patients with muscle-invasive or advanced urothelial cancers treated between the years 2005 and 2012, across 28 different international sites. For our study, we included patients if they had a diagnosis of metastatic urothelial carcinoma, if they had received platinum-based chemotherapy in the first-line setting for metastatic disease, and if they had received 2 or more cycles of additional chemotherapy in the later line setting. We did exclude patients if they had previously received platinum-based chemotherapy in the non-metastatic setting. For example, patients who previously had localized disease and received chemotherapy in the perioperative setting.

What notable differences did you observe between patients treated with platinum-based chemotherapy versus those who are not?

Patients treated with subsequent platinum-based chemotherapy had better overall survival than those patients that were treated with a non-platinum-based regimen. So, the median overall survival for the subsequent platinum group was 7.9 months compared to 5.5 months in the non-platinum group. This difference was statistically significant and the multivariable model that adjusted for baseline characteristics in the 2 groups. Also, we found that more patients in the subsequent platinum group derived clinical benefit, which we defined as achieving stable disease, partial response, or complete response to chemotherapy, compared to the non-platinum group, so 57% of patients achieved this clinical benefit in the platinum group versus only 45% in the non-platinum group.

Were there any baseline characteristics that impacted the results for these patients in either arm?

Since this was a retrospective study, we would expect that there would be some differences in baseline characteristics between the patients who received subsequent platinum-based chemotherapy and those that received non-platinum-based chemotherapy. For example, one might expect that the group that received subsequent platinum would be more fit than the group that received non-platinum or maybe that they had a better response to platinum-based chemotherapy in the first line setting that would make providers more willing to try platinum agents again.

We did find that patients in the subsequent platinum group at baseline had higher hemoglobin values. They were more likely to have achieved stable disease partial response or a complete response to first-line platinum and they had a longer amount of time elapse between completing first-line platinum-based chemotherapy in the metastatic setting and subsequent chemotherapy. However, we didn't find any difference in ECOG performance status or in comorbidity burden, as estimated by the Charlson Comorbidity Index between the 2 groups. And the difference in overall survival that I mentioned that was seen between the 2 groups remained statistically significant after adjusting for these baseline characteristics in a multivariable model, with the exception of hemoglobin, which we couldn't include in the multivariable model due to missing values.

We also did find in subgroup analysis that different baseline characteristics were associated with achieving stable disease, partial response, or complete response with subsequent chemotherapy. So in the subsequent platinum group, we found that patients were more likely to achieve stable disease, partial response, or complete response if they had done the same with first-line platinum-based chemotherapy, if there was a longer time between receipt of first-line platinum-based chemotherapy and subsequent chemotherapy, and also if they did not have liver metastases. But these same associations were not seen for the non-platinum group.

Overall, what do these findings suggest?

So overall, these findings suggest that in the situation where providers are considering further chemotherapy for a patient who has received first-line, platinum-based chemotherapy for metastatic disease, they should lean towards a platinum-based regimen again, if the patient is fit enough to tolerate it. Also, our subgroup analysis suggests that they might expect a higher likelihood of clinical benefit to the patient, if the patient had a good response to first-line platinum, if it has been a longer time since first-line platinum and also if the patient doesn't have any liver metastases.