ASCO Michigan 2024: Dr. Shao Discusses Abstracts in Metastatic Urothelial Carcinoma

Presenter:

Yusra F. Shao, MD, Karmanos Cancer Institute

Conference:

ASCO Direct™ Michigan

The Bottom Line:

Results from three clinical trials presented at this year’s American Society for Clinical Oncology (ASCO) Meeting focused on current treatments for advanced bladder cancer (urothelial carcinoma, UC), which include enfortumab vedotin (EV) and combination therapy with nivolumab immunotherapy and gemcitabine/cisplatin (Nivo+Gem/Cis). Results from these trials, as summarized by oncologist Dr Yusra F. Shao, provide new insights into quality of life issues such as improvement in pain, and management of adverse events for patients on EV, as well as a subgroup of UC patients who may have a greater benefit with the Nivo+Gem/Cis regimen. 

Background:

The standard of care (SOC) treatment for patients with bladder cancer which has spread beyond the primary site of the tumor (metastatic urothelial carcinoma, mUC) had been platinum-based chemotherapy, with or without maintenance immunotherapy (avelumab).  Recent results however, showed that enfortumab vedotin (EV), in combination with another immunotherapy (pembrolizumab, P) led to improved progression-free survival (PFS), as well as overall survival (OS) compared to SOC platinum-based chemotherapy.  In addition, the combination of nivolumab immunotherapy and gemcitabine/cisplatin chemotherapy (Nivo+Gem/Cis) was also shown to improve both PFS and OS compared to chemotherapy alone. As such, either of these two options can now be considered for patients with mUC who are considered eligible for cisplatin chemotherapy (“cis-eligible”).  In her presentation at the ASCO Direct™ Michigan conference, Dr. Yusra F. Shao, MD, from Karmanos Cancer Institute, summarized findings from 3 abstracts on mUC, highlighting key take-aways and implications for current clinical practice.

Patient-Reported Outcomes for mUC Patients on Enfortumab Vedotin plus Pembrolizumab (EV+P)[Abstract #4502; Gupta et al.]

Previous results from the EV-302 Trial had shown that EV+P improved PFS and OS in (cis)-eligible and (cis)-ineligible patients as compared to chemotherapy.  The current results detailed patient-reported outcomes of time to pain progression (defined as time to worsening pain or initiation of opioids), and the change from baseline in pain scores, which were key secondary endpoints in the trial.  The results showed no significant difference in time to pain progression, and neither group had a change in pain score that was considered clinically meaningful (defined as a 2 point change in score).  When examining a subgroup of patients with moderate to severe pain at baseline, however, there was a greater improvement in moderate to severe pain, and a clinically meaningful improvement in quality of life (QoL) measures for patients on EV+P relative to those on SOC chemotherapy.  Summarizing the results, Dr Shao noted that patients with mUC and moderate to severe pain at baseline receiving EV+P experience not only improved survival compared to chemotherapy but also improved pain and QoL measures, which further supports the use of EV+P as the new SOC in mUC.  She also noted having seen such improvements in pain and QoL measures for some of her own patients on EV+P.

 Impact of Exposure on Outcomes with EV  [Abstract #4503; Petrylak et al.]

Dr Shao noted that previously reported safety results from EV-302 showed that 40% of patients did require a dose reduction during their treatment with EV, and up to 35% required treatment discontinuation due to adverse events such as neuropathy and rash, with peripheral neuropathy being the most common cause of treatment discontinuation. The current abstract sought to determine the relationship between overall EV exposure and efficacy, using pooled results from 3 clinical trials, 2 examining use of EV as a single agent, and 1 comparing EV to chemotherapy.  The results showed, overall, that similar response rates and OS were seen in patients within the top 2 groups for EV exposure, suggesting no decrement in EV efficacy after dose reduction.  Based on these results, and having noted the occurrence of these toxicities in her own patients on EV, Dr Shao suggested “Our patients will clinically require dose reductions for EV due to toxicity… and we should feel comfortable doing that, doing that early, and perhaps even considering frail patients being started at a lower dose…”

Nivo+Gem/Cis in Node-Only Metastatic Disease [Abstract #4509; Galsky et al.]

While long term survival for patients with mUC treated with chemotherapy is limited, some studies have shown that outcomes can be improved for patients whose disease spread is limited to the lymph nodes (LN only disease) with consolidative surgery.  Studies have also shown better survival for those with a complete response (>90% response) to initial chemotherapy. In the CheckMate 901 (CM901) Trial, Nivo+Gem/Cis was shown to improve both PFS and OS relative to Gem/Cis chemotherapy alone in cis-eligible patients.  In the current abstract, long term outcomes were studied in patients with LN only mUC who had a complete response to their initial treatment with Nivo+Gem/Cis in CM901.  The results showed that this subgroup of patients had a much better response to Nivo+Gem/Cis (median OS, 46.3 vs. 24.9 months) relative to the results in the CM901 population overall (median OS, 21.7 vs. 18.9 months).  In addition, in the LN only population, complete response rate with Nivo+Gem/Cis was 63% relative to the overall population, in which it was 21.7%.  Commenting on these results, Dr Shao noted that mUC patients with LN only disease represents a subset of patients with an especially good prognosis, and excellent response to treatment with Nivo+Cem/Cis (as well as EV+P, as seen in the EV-302 trial).

Conclusions and Faculty Insights:

When evaluating treatment options for upfront therapy in mUC, Dr Shao noted that, for patients receiving EV+P, pain and QoL scores do improve in those with moderate to severe pain scores at the start of treatment, and, while reducing the dose of EV is often necessary for her patients for adverse events like rash and neuropathy, clinicians can be reassured that reduced dosing does not impact clinical efficacy of EV.  Dr Shao also noted that Nivo + Gem/Cis is another excellent option for patients with mUC who are cis-eligible, but especially for those patients with LN only disease.

In terms of how to select between these two options, Dr Shao noted that while either treatment represents an excellent option over the previous SOC of platinum-based chemotherapy, Nivo + Gem/Cis also offers the benefit of fixed cycles of chemotherapy, and this is sometimes more desirable for patients. In addition, she notes that surgery can also be considered for those patients with limited metastatic involvement (“oligometastatic disease”) who have a complete response to their initial systemic treatment.

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Speaker Disclosure:  Dr. Shao reported no relevant disclosures for this presentation.