In a latest interview, Joaquim Bellmunt, MD, PhD, affiliate professor, Drugs, Harvard Medical College and director, Bladder Most cancers Program, Beth Israel Deaconess Medical Heart, mentioned long-term information from the part 3 JAVELIN Bladder 100 trial of frontline upkeep avelumab (Bavencio) in sufferers with metastatic urothelial most cancers (mUC) who acquired first-line chemotherapy.1
The interview passed off earlier this yr throughout the 2022 GU Cancers Symposium, the place the up to date findings have been shared. Bellmunt additionally previews extra information from the JAVELIN Bladder 100 trial that will likely be offered on the 2022 ASCO Annual Assembly.
As a recap, what was noticed within the major evaluation of the JAVELIN Bladder 100 trial?
Bellmunt: The first evaluation of survival confirmed that the median total survival within the sufferers who obtain avelumab upkeep was 21.4. And in one of the best supportive care arm, it was 14.3 months. Meaning a 7-month enchancment in median total survival with a hazard ratio of 0.69.
The primary evaluation was executed in October 2019. And the evaluation offered at AUA was after not less than 2 years of follow-up with a knowledge cutoff of June 2021. So, with that, we see that the long-term follow-up of this trial is confirming the outcomes that have been already revealed within the New England Journal in 2020.
How was the long-term evaluation of the JAVELIN Bladder 100 trial carried out?
This trial was designed in sufferers with metastatic bladder most cancers that have been receiving remedy with platinum gemcitabine or carboplatin/gemcitabine and if the sufferers did not progress, which means if the sufferers have been in a position to acquire partial response, secure illness, or full response, then the sufferers have been randomized to obtain upkeep avelumab plus finest supportive care.
With this latest evaluation, what we’ve seen is that the median total survival within the avelumab upkeep is 23.8 months, and in one of the best supportive care arm it’s like 15.0 months, which means an 8-month distinction within the median. The hazard ratio is kind of the identical at 0.76, and the profit has been seen throughout totally different subgroup of sufferers. Unbiased of sufferers responding or not responding, all sufferers benefited from receiving avelumab upkeep.
The profit was seen in survival and was additionally seen in progression-free survival. So, on this up to date evaluation, the PFS within the total inhabitants of sufferers receiving avelumab was 5.5 months, it was 2.1 months in sufferers receiving finest supportive care. So, a considerable PFS prolongation was seen in these sufferers receiving avelumab upkeep.
One other evaluation being offered throughout AUA is round subsequent remedy the sufferers acquired as a result of clearly, we all know {that a} specific remedy generally impacts total survival. And what we noticed within the evaluation was that in sufferers that have been assigned obtain avelumab upkeep, 11.4% of sufferers acquired subsequent remedy with a PD-1 or PD-L1 inhibitor whereas in one of the best supportive care 53% of sufferers acquired a PD-1/PD-L1 inhibitor. Because of this giving upkeep avelumab sooner supplies a survival benefit.
What did longer follow-up train you about frontline upkeep avelumab remedy on this affected person inhabitants?
We now know that the share of sufferers who’re alive on this trial or at years is 49.8% within the avelumab upkeep inhabitants versus 38.4% in one of the best supportive care arm. We’ve not seen surprising hostile occasions, so it confirms the security of one of these method when utilizing swap upkeep to handle sufferers who don’t progress to chemotherapy within the first line.
These outcomes help the advice of avelumab first-line upkeep as an ordinary of care in urothelial most cancers, sufferers with metastatic illness receiving chemotherapy with platinum-based remedy, carboplatin, or cisplatin, and people who should not progressing. So, it is a new normal of care when managing metastatic bladder most cancers sufferers.
So, now the idea of avelumab upkeep as the usual of care has been included in all the rules.
What different kind of sub evaluation will likely be necessary from this examine?
Upcoming on the ASCO 2022 Annual Assembly, we’re going to replace extra information on what is the position of second-line therapies if the affected person will obtain chemotherapy as rescue remedy as a result of that is one thing that we do not know presently.
What can we do after the affected person has acquired chemotherapy, adopted by upkeep avelumab and so they progress? Some pointers say the following step is enfortumab vedotin, and in reality, there’s very restricted information on that. Within the evaluation that’s going to be offered at ASCO, we’re going to see the outcomes of a affected person receiving rechallenge with chemotherapy as a result of these sufferers have already responded to first-line chemotherapy, or not less than they haven’t progressed. The sufferers have a vacation interval the place they obtain avelumab upkeep after which once they progress, some sufferers can obtain once more platinum-based remedy. And that is one thing that we do not know, all these information have to be collected. So, what is the end result in these sufferers, both it is good to obtain subsequent chemotherapy, or perhaps there’s a probability to provide a focused remedy, however we presently do not know.
We all know that the blood most cancers panorama is altering so rapidly, we’re ready for brand new trials within the first line combining immunotherapy with an antibody-drug conjugate that could be altering the longer term in the way in which that we deal with first-line metastatic sufferers. As extra information are being analyzed from these trials, we can design one of the best technique by way of the best way to sequence remedy in sufferers with bladder most cancers as a way to present improved survival whereas preserving the standard of life. That is a vital factor.
Reference
1. Powles T, Park SH, Voog E, et al. Avelumab first-line (1L) upkeep for superior urothelial carcinoma (UC): long-term follow-up outcomes from the JAVELIN Bladder 100 trial. J Clin Oncol. 2022;40(suppl 6):487. doi:10.1200/JCO.2022.40.6_suppl.487
