At the 2023 ASCO Genitourinary Cancers Symposium, Srikala Sridhar, MD, Princess Margaret Cancer Center, Toronto, Ontario, Canada shares post hoc analyses of long-term outcomes by first-line chemotherapy regimen and overall survival from the start of first-line chemotherapy in the JAVELIN Bladder 001 trial. This analysis found, regardless of which chemotherapy regimen was used in the first-line setting, gemcitabine-cisplatin or gemcitabine-carboplatin, maintenance avelumab provided similar overall survival and progression-free survival benefits. Overall survival was also longer with avelumab, vs with best supportive care alone, regardless of first-line chemotherapy regimen.

Dr Sridhar concluded "These results further support avelumab first-line maintenance as the standard of care in patients with metastatic urothelial carcinoma who do not have evidence of disease progression following frontline platinum-based chemotherapy."

Transcript:

Hi, my name is Dr. Srikala Sridhar. I'm a medical oncologist at the Princess Margaret Cancer Center. This year at ASCO GU 2023, we presented the abstract: Avelumab first-line maintenance for advanced urothelial carcinoma: Long-term follow up from the JAVELIN Bladder 100 trials in subgroups defined by first-line chemotherapy regimen and an analysis of overall survival from start of first-line chemotherapy. In the randomized, stage 3 Javelin Bladder 100 trials, avelumab first-line maintenance plus best supportive care, significantly prolonged overall survival and progression-free survival from start of maintenance versus best supportive care alone in patients with metastatic urothelial carcinoma that did not have disease progression with front-line platinum-based chemotherapy. Results from this trial led to approval of avelumab first-line maintenance in various countries worldwide. With long-term follow-up, median overall survival was 23.8 months vs 15 months, respectively, and the median investigator-assessed progression-free survival was 5.5 vs 2.1 months, respectively.

In this post-hoc analysis, we looked at outcomes from the start of maintenance in subgroups defined by first-line chemotherapy regimen, be it gemcitabine-cisplatin or gemcitabine-carboplatin, and we looked at overall survival from the start of first-line chemotherapy in the overall population and by first-line chemotherapy regimen. Essentially, what we found was that maintenance avelumab was beneficial regardless of the first-line chemotherapy regimen. Of course, patients who received gemcitabine and carboplatin tended to be a little bit older, a little bit frailer, and had worse kidney function, which is not surprising. When we look at overall survival in the group that received gemcitabine and cisplatin, this came out to be 25.1 months in patients who had avelumab maintenance versus 17.5 months in patients who received best supportive care alone. The hazard ratio there was 0.79. When we look at the group that received gemcitabine and carboplatin, these numbers were slightly lower, 20.8 months for the group that received avelumab maintenance compared to 13 months in the group that received best supportive care alone. Hazard ratio there was 0.69. We also saw similar findings with investigator-assessed progression-free survival from the start of maintenance where the numbers were, again, slightly higher in the group that received gemcitabine and cisplatin compared to the group that received gemcitabine and carboplatin. Nonetheless, we saw a benefit to maintenance avelumab regardless of the first-line regimen in this post hoc, long-term, exploratory analysis.

In this abstract, we also reported on median overall survival measured from the start of front-line chemotherapy. Of course, remember in the original trial the time started ticking at the time that patients received maintenance. This was a subset analysis of patients who made it onto this trial, those who had not had any evidence of disease progression following front-line chemotherapy. We looked at overall survival measured from the start of first-line chemotherapy and found that it was also longer with avelumab plus best supportive care versus best supportive care alone, again, irrespective of the first-line chemotherapy regimen that was received. Long-term safety was similar in both the cisplatin plus gemcitabine and carboplatin plus gemcitabine subgroups.

It is interesting to look at the overall survival in the group of patients that made it onto this study from the beginning of chemotherapy. These numbers are now starting to approach 29.7 months versus 20.5 months. So this is really the group of patients who did not have any disease progression on front-line chemotherapy and made it onto this study, and I think this really highlights some of the advances that we've made in this disease over the last few years. Until quite recently, we were quoting overall survivals of only about 14 to 15 months. Of course, again, I highlight this is a subset of patients, but it's still really exciting to see the advances that are being made in terms of overall survival and outcome in this disease.

When we look specifically at the gemcitabine and cisplatin group from the time of front-line chemotherapy, the median overall survival was 31 months compared to 23 months in the group that received best supportive care alone. And when we look at the group that got gemcitabine and carboplatin, we see that the survival there was 25.8 months compared to 17.6 months. Again, patients receiving gemcitabine and cisplatin tend to do a little bit better. Now, whether that's due to the disease or due to the patients themselves is hard to know. In my practice, I tend to offer gemcitabine and cisplatin wherever possible to maximize the benefit the patient may be able to get from chemotherapy.

In summary, long-term follow-up from the JAVELIN Bladder 100 trial, with a median follow-up of greater than or equal to 38 months, confirmed that avelumab first-line maintenance provided similar overall survival and progression-free survival benefits irrespective of whether patients received standard of care first-line cisplatin- or carboplatin-based chemotherapy. The long-term safety of avelumab first line maintenance was similar in patients who had received first-line cisplatin or carboplatin plus gemcitabine. In the overall population, median overall survival with the full JAVELIN Bladder regimen, first-line cisplatin- or carboplatin-based chemotherapy followed by avelumab first-line maintenance was 29.7 months. Overall survival was longer with avelumab irrespective of the first-line chemotherapy regimen.

These results further support avelumab first line maintenance as the standard of care in patients with metastatic urothelial carcinoma who do not have evidence of disease progression following front-line platinum-based chemotherapy and provide a benchmark for ongoing and future clinical trial outcomes.

Thank you for your attention.

Source:

Sridhar SS, Powles T, Gupta S, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up from the JAVELIN Bladder 100 trial in subgroups defined by 1L chemotherapy regimen and analysis of overall survival (OS) from start of 1L chemotherapy. J Clin Oncol. 2023;41(6_suppl):508. doi:10.1200/JCO.2023.41.6_suppl.508