Pembrolizumab (Keytruda) has better response rates than ipi and has fewer side effects...not really news...but still good to know! In this study, Pembro had response rates of about 36% no matter the dosing frequency, while ipi only reached 13%. Interestingly, responders without further progression was higher with ipi, though by a small margin, at 75% vs 72 and 69% for pembro.
Pembrolizumab
versus ipilimumab for advanced melanoma: Final overall survival analysis of
KEYNOTE-006. ASCO 2016. #9504. J Clin Oncol 2016. Scachter, Ribas, Long, et al.
Background: In the phase III KEYNOTE-006
study (NCT01866319), pembro (anti–PD-1) provided superior OS and PFS and a
lower incidence of grade 3-5 treatment-related AEs compared with ipi
(anti–CTLA-4) in patients (pts) with advanced melanoma and ≤ 1 prior therapy.
Here, we present the final OS analysis. Methods: 834 pts were randomized
1:1:1 to 24 mo of pembro 10 mg/kg Q3W or Q2W or to 4 doses of ipi 3 mg/kg Q3W.
Clinically stable pts with radiologic progression could receive treatment until
confirmed progression. Response was assessed per RECIST v1.1 by central review
at wk 12, every 6 wk until wk 48, then every 12 wk thereafter. Survival
follow-up was every 12 wk. Final OS analysis occurred after all pts were
followed for ≥ 21 mo. Differences in OS were assessed in the intention-to-treat
population using the stratified log-rank test with the Hochberg procedure. Results:
As of Dec 3, 2015, median follow-up duration was 22.9 mo and 383 pts had died.
Pembro continued to provide superior OS, PFS, and ORR over ipi, with no
difference between pembro schedules (Table). Median OS was not reached for
pembro vs 16.0 mo with ipi; estimated 24-mo OS rates were 55% and 43%,
respectively. The PFS KM curves appeared to flatten after ~20 mo for all arms,
with estimated 24-mo rates of ~30% for pembro and 14% for ipi. KM estimates
suggest ~70% of responding pts have a response lasting greater than or equal to
72 wk. There was 1 treatment-related death (sepsis in the pembro Q2W arm). The
safety profile was consistent with that previously reported. Conclusions:
With an additional 9 mo of follow-up, median OS was not reached for pembro, and
the superiority of pembro over ipi for advanced melanoma was confirmed. Coupled
with the durability of response and manageable safety profile, these data
support pembro as a standard of care for advanced melanoma. Clinical trial
information: NCT01866319
Pembro 10 Q2W
N = 279 |
Pembro 10 Q3W
N = 277 |
Ipi
N = 278 |
|
OS,
median, mo
|
|||
Median,
mo
|
NR
|
NR
|
16.0
|
24-mo
rate, %
|
55.1
|
55.3
|
43.0
|
HRa
(95% CI)
|
0.68
(0.53-0.87)
|
0.68
(0.53-0.86)
|
—
|
PFS,
median, mo
|
|||
Median,
mo
|
5.6
|
4.1
|
2.8
|
24-mo
rate, %
|
31.2
|
27.8
|
13.5
|
HRa
(95% CI)
|
0.61
(0.50-0.75)
|
0.61
(0.50-0.75)
|
—
|
ORR,
%
|
36.9
|
36.1
|
13.3
|
Responders
without further progression, %
|
72.8
|
69.0
|
75.7
|
Pembrolizumab
(pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the
KEYNOTE-029 expansion cohort.
ASCO 2016. #9506. J Clin Oncol
2016. Long, Atkinson, Cebon, et al.
Background: Pembro (MK-3475), an
anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and
PD-L2, is approved in several countries for treating advanced melanoma. In
KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a
phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and
standard-dose ipi showed higher ORR and longer PFS than either checkpoint
inhibitor alone but was associated with increased toxicity. Preliminary data
from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose
pembro + reduced-dose ipi was safe and provided robust antitumor activity.
Here, we present data from a larger population of patients (pts) treated with
pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts
had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior
immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1
mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity,
progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk
until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled
in the expansion, 107 had greater than or = to, 18 wk of follow-up (median 6.4
mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for
analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant,
13% received greater than or = to, 1 prior therapy, and 12% received a prior
BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, greater than 1%
staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi
doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related
AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to
discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and
pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated
AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts.
ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central
review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg
in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile
and provides robust antitumor activity in pts with advanced melanoma. Clinical
trial information: NCT02089685
The following has been beat to death by the media and Merck...but still pretty damn good..... Interesting that the OS data at 36 months was NO different for the ipi treated and ipi naive patients.
Three-year
overall survival for patients with advanced melanoma treated with pembrolizumab
in KEYNOTE-001. ASCO 2016. #9503. J Clin Oncol 2016. Robert, Tibas, Hamid, Daud, Wolchok, Weber, et
al.
Background: The anti–PD-1 antibody
pembro (pembro; MK-3475) prevents PD-1 from binding to its ligands, PD-L1 and
PD-L2, and is approved for treating advanced melanoma at a dose of 2 mg/kg
every 3 wk (Q3W). Pembro demonstrated superior PFS over chemotherapy for
ipilimumab (ipi)-refractory melanoma (KEYNOTE-002) and superior OS and PFS over
ipi for advanced melanoma (KEYNOTE-006). We present 3-year OS data for all
patients (pts) with melanoma enrolled in the phase 1b KEYNOTE-001 study
(NCT01295827). Methods: Pts were enrolled in ipi-naive and ipi-treated
cohorts and received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable
toxicity, progression, or investigator decision. Clinically stable pts with
radiographic progression could remain on pembro until progression was
confirmed. Response was assessed by RECIST v1.1 every 12 wk. After pembro
discontinuation, pts were contacted to assess survival every 3 mo. OS was
estimated using the Kaplan-Meier method. Results: Of the 655 pts
enrolled, 24% had BRAFV600mutation, 78% had stage M1c
disease, 38% had elevated LDH, 75% had greater than or = to, 1 prior therapy, and 52% had prior ipi.
As of the Sep 18, 2015, data cutoff date, median follow-up duration was 32 mo
(range 24-46) and 358 (55%) pts had died. The 36-mo OS rate was 40% and median
OS was 23.8 mo, with similar results for each dose.
36-mo OS rates were 41% in both ipi-treated and ipi-naive pts and 45% in
treatment-naive pts. Examination of the OS curve suggests a long-term
OS benefit for a fraction of pts treated with pembro. Additional data,
including PFS, ORR, duration of response, and safety, will be available for
presentation. Conclusions: Pembro provides long-term survival benefit in
pts with ipi-naive and ipi-treated advanced melanoma, with 40% of pts alive at
3 years. These data support the use of pembrolizumab in pts with advanced
melanoma regardless of prior treatment. Clinical trial information: NCT01295827
N
|
Median OS
(95% CI), mo |
24-mo OS Rate, %
|
36-mo OS Rate, %
|
|
Pembro
2 Q3W
|
162
|
23.5
(18.3-35.0)
|
49
|
38
|
Pembro
10 Q3W
|
313
|
22.9
(18.5-31.1)
|
49
|
39
|
Pembro
10 Q2W
|
180
|
25.9
(18.9-41.8)
|
52
|
43
|
Ipi
treated
|
342
|
20.0
(17.8-27.1)
|
46
|
41
|
Ipi
naive
|
313
|
28.8
(23.1-32.2)
|
54
|
41
|
Treatment
naive*
|
149
|
32.0
(27.1-NR)
|
60
|
45
|
So the games have begun. I will group and report out data as best I can. My thoughts, or data I feel hits the crux of the matter, will be in red. Otherwise...the abstracts are presented as is. Roll on ratties....roll on!!!! - c
All I can say is you are awesome! Keep it coming❤️
ReplyDeleteThanks so much, Celeste!
ReplyDelete