Sufferers with metastatic renal cell carcinoma (RCC) — a kind of kidney most cancers — didn’t expertise advantages after receiving a mixture of Opdivo (nivolumab) and Fotivda (tivozanib). Sufferers beforehand skilled illness development (worsening) on or after remedy with a PD-(L)1 inhibitor.
Findings have been based mostly on the part 3 TiNivo-2 research and offered on the 2024 ESMO Congress.
Examine highlights:
- Sufferers with metastatic renal cell carcinoma (RCC) who obtained Opdivo and Fotivda after experiencing illness worsening on a PD-(L)1 inhibitor didn’t expertise improved outcomes.
- Fotivda alone was proven to be a more practical possibility for these sufferers in comparison with the mix remedy.
- The research means that rechallenging sufferers with one other immune checkpoint inhibitor (ICI) after development on one is mostly not advisable.
- The optimum sequence of therapies for sufferers with RCC who progress on an ICI stays unsure.
“TiNivo-2 was the primary part 3 trial to guage the efficacy and security of a PD-1 inhibitor following development on or after remedy with a PD-[L]1 remedy,” Dr. Toni Choueiri of Dana-Farber Most cancers Institute in Boston, stated in a presentation of the info on the assembly. “TiNivo-2 is a damaging research, however I strongly imagine it’s necessary. It’s practice-changing, and it ought to make us suppose twice now. … These outcomes help [Fotivda] monotherapy at 1.34 kilograms as a second-line remedy possibility in sufferers following development on earlier immune checkpoint inhibitor [ICI] remedy.”
At a median follow-up of 11.8 months within the Fotivda plus Opdivo group with 171 sufferers and 12.5 months within the Fotivda monotherapy group with 172 sufferers, the median progression-free survival (PFS; time sufferers reside with out their illness worsening or spreading) was not improved with the doublet versus monotherapy. Findings from the first evaluation of PFS, which was the research’s major purpose, revealed that the median PFS was 5.7 months for the mix versus 7.4 months for Fotivda alone within the intention-to-treat inhabitants.
“This trial confirms and expands key conclusions from the [phase 3] CONTACT-03 research. [TiNivo-2] is the second part 3 trial in RCC and strong tumors that means that ICI rechallenge must be usually discouraged no matter remedy sequence. We [also] imagine that the diminished dose of [Fotivda] within the mixture [group] might have impacted the efficacy, and that displays within the decrease median PFS [observed],” Choueiri stated.
Affected person Traits and Examine Findings
Sufferers with regionally superior or metastatic clear cell RCC have been enrolled following illness development on one or two traces of remedy, one in all which was an ICI they progressed on throughout or following at the least six weeks of remedy.
Sufferers wanted to have an ECOG efficiency standing of 0 or 1, that means they have been in a position to carry out every day duties independently; measurable illness; and a time from the quick prior line of remedy obtained to their random project of six months or much less.
“What stays unknown, largely, is the optimum sequence [of therapies in RCC] in sufferers whose illness has progressed after remedy with an ICI. If we rechallenge with the identical or a distinct ICI, does this enhance medical outcomes?” Choueiri requested. He famous that following the encouraging efficacy seen within the part 1/2 TiNivo research with [Fotivda] plus nivolumab, TiNivo-2 was initiated.
Choueiri famous that the diminished dose was agreed upon with regulatory authorities as a result of potential danger of elevated charges of grade 3/4 (extreme to life-threatening) hypertension (hypertension) within the mixture remedy group.
The trial’s important purpose was PFS and secondary targets have been total survival (OS; time sufferers reside, no matter illness standing), goal response fee (ORR; proportion of sufferers whose tumors shrunk or disappeared), length of response and security/tolerability.
The median age of sufferers within the Fotivda plus Opdivo group was 64 years in contrast with 63 years within the Fotivda monotherapy group. Most sufferers have been male (73% for the mix versus 78% for Fotivda monotherapy), White (65% versus 62%), had an ECOG efficiency rating of 1 (55% versus 51%), obtained one prior line of remedy (65% versus 61%) and obtained an ICI as their most up-to-date remedy (71% versus 71%). Moreover, sufferers had favorable- (18% versus 18%), intermediate- (67% versus 66%) and poor- (16% versus 16%) danger illness and roughly one-third of sufferers didn’t obtain a previous VEGFR-TKI (31% versus 31%).
Extra Survival Findings for Sufferers With Metastatic Kidney Most cancers
When inspecting PFS by line of remedy, greater PFS charges have been noticed within the second-line setting, though Fotivda monotherapy outdid Fotivda plus Opdivo. The median PFS amongst sufferers who obtained Fotivda plus Opdivo (111 sufferers) within the second-line setting was 7.3 months versus 9.2 months amongst sufferers handled with the monotherapy on this setting.
Those that obtained remedy in TiNivo-2 as third-line remedy skilled a median PFS of 4.8 months within the doublet group of 60 sufferers versus 5.5 months within the monotherapy group with 67 sufferers.
“I imagine [these data] debunk the speculation that break and rechallenge is healthier,” Choueiri added.
Information revealed that the median OS was 17.7 months within the Fotivda plus Opdivo group in contrast with 22.1 months within the Fotivda monotherapy group. Nevertheless, Choueiri famous that OS knowledge weren’t mature as a result of on the knowledge cutoff, solely 32% of occasions had occurred in sufferers.
Moreover, the ORR was 19.3% within the doublet group versus 19.8% within the singlet group. One affected person in every group achieved a whole response, that means they not confirmed indicators of most cancers. Sufferers additionally skilled steady illness (43.3% versus 47.1%), progressive illness (28.7% versus 25%) or weren’t evaluable (8.8% versus 8.1%). The median length of response was 15.77 months with the doublet in contrast with 9.66 months with monotherapy.
Security Outcomes in Sufferers With Metastatic Kidney Most cancers
Unwanted side effects resulting in loss of life occurred in seven sufferers within the doublet group and 5 sufferers within the Fotivda monotherapy group. Sufferers skilled grade 2 (severe) or higher unwanted side effects (61% for the doublet versus 60% for the singlet), severe unwanted side effects (32% versus 37%) and treatment-emergent unwanted side effects resulting in discontinuation (16% versus 19%), dose interruption (49% versus 54%) and dose discount of Fotivda (11% versus 22%). The median length of remedy was 6.3 months and seven.4 months, respectively.
The commonest any-grade unwanted side effects noticed have been hypertension (37% versus 40%), fatigue (29% versus 40%), diarrhea (30% versus 36%) and nausea (16% versus 28%), within the doublet and monotherapy teams, respectively.
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