Novartis’ highly-touted radionuclide remedy Pluvicto met its major endpoint in a section 3 trial as a second-line remedy for PSMA-positive metastatic castration-resistant prostate most cancers (mCRPC), however might not be the house run the corporate is hoping for.
The PSMAfore trial met its major goal of enhancing radiographic progression-free survival (rPFS) in sufferers beforehand handled with androgen receptor pathway inhibitor (ARPI) remedy, with a 59% discount on that endpoint in comparison with a change in ARPI – at present the principle remedy technique.
That distinction was seen at 7.3 months of follow-up, and the profit was confirmed in a second evaluation carried out at 15.9 months when the median rPFS was simply over 12 months with Pluvicto (lutetium [lu177] vipivotide tetraxetan) and 5.6 months within the management group.
Presenting the information on the ESMO congress, co-principal investigator Dr Oliver Sartor of Tulane College Faculty of Medication within the US described the profit as “spectacular” and in keeping with Novartis’ open-label VISION trial of Pluvicto in the identical remedy setting that was reported final yr.
The outcomes may “change the remedy paradigm for superior prostate most cancers by permitting sufferers to probably keep away from or delay taxane-based chemotherapy, which carries a heavy burden of unwanted side effects,” stated Novartis’ head of oncology growth Jeff Legos.
There was one subject within the PSMAfore trial, nevertheless, in that its means to offer a studying on total survival was stymied by a excessive charge of crossover from the ARPI group to Pluvicto earlier than the second interim evaluation.
After correcting for that crossover there was a pattern in the direction of enchancment, and Novartis remains to be following up the survival knowledge however isn’t anticipating an replace on that till subsequent yr. The corporate has indicated it would maintain off on submitting for approval of the drug as a second-line remedy till it’s accessible.
“The outcomes from the PSMAfore trial are attention-grabbing, however their influence on medical observe can be restricted with out affirmation of an total survival (OS) profit,” remarked Prof Nicholas James from the Institute of Most cancers Analysis and Royal Marsden Hospital within the UK, ESMO’s discussant for the information.
“We additionally want to think about price and the chance that remedy within the comparator arm was suboptimal,” added James. “Switching from one ARPI to another is understood to be a method with restricted efficacy in comparison with switching to chemotherapy.”
Pluvicto is seen as essentially the most promising drug in Novartis’ radionuclide arsenal, and is already permitted as a later-line remedy for PSMA-positive mCRPC after each ARPI and taxane-based chemotherapy have been tried. It’s rising rapidly, with annual gross sales already approaching blockbuster ranges in its first full yr available on the market, coming in at $707 million within the first 9 months of this yr.
The drug was added to Novartis’ portfolio by means of a $2.1 billion acquisition of Endocyte in 2018, and the drugmaker has stated it thinks gross sales may ultimately prime $2 billion if it expands into earlier strains of remedy in mCRPC in addition to metastatic hormone-sensitive prostate most cancers.