Yes. I think the results ratties provided have finally gotten it through most researchers heads (though not the heads of all oncologists) that targeted therapy (via the BRAF/MEK combo for BRAF positive melanoma peeps) and immunotherapy WORK IN THE BRAIN!!!! I have been reporting on this trial CheckMate 204 since 2015. Now, there's this:
Efficacy and safety of the combination of
nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma
brain metastases (CheckMate 204). 2019 ASCO. Tawbi, Forsyth, Hodi...Hamid...Postow, Pavlick...et al. J Clin Oncol 37, 2019 (suppl; abstr 9501)
Background: We previously reported efficacy and safety of NIVO+IPI in patients (pts) with untreated, asymptomatic, melanoma brain metastases (MBM) from the CheckMate 204 study. Here, we provide the first report of NIVO+IPI in pts with symptomatic MBM, and report updated data in pts with asymptomatic MBM. Methods:In this phase II trial, pts with greater than/= to 1 measurable, nonirradiated MBM 0.5–3.0 cm were enrolled into two cohorts: (1) those with no neurologic symptoms or steroid Rx (asymptomatic; cohort A); and (2) those with neurologic symptoms, whether or not they were receiving steroid Rx (symptomatic; cohort B). In both cohorts, pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, then NIVO 3 mg/kg Q2W until progression or toxicity. The primary endpoint was intracranial clinical benefit rate (CBR; proportion of pts with complete response [CR] + partial response [PR] + stable disease [SD] greater than/= to 6 mo). As of the clinical cutoff date on May 1, 2018, all treated pts (101 in cohort A and 18 in cohort B) had been followed for ~6 mo or longer. Results: In this updated analysis of cohort A (median follow-up of 20.6 mo), the CBR was 58.4% (Table). In cohort B, pts received a median of 1 NIVO+IPI dose and 2 of 18 pts (11%) received all 4 doses. At a median follow-up of 5.2 months in cohort B, intracranial objective response rate was 16.7% and the CBR was 22.2%. Grade 3/4 adverse events occurred in 54.5% of pts in cohort A and in 55.6% of pts in cohort B (6.9% and 16.7% in the nervous system, respectively), with one death related to treatment in cohort A (immune-related myocarditis). Conclusions: In pts with asymptomatic MBM, our updated results show a high rate of durable intracranial responses, further supporting NIVO+IPI as a first-line treatment in this population. Intracranial antitumor activity was observed with NIVO+IPI in pts with symptomatic MBM, but further study is needed to understand the biologic mechanisms of resistance to immunotherapy and to improve treatments in this challenging population. Clinical trial information: NCT02320058
Intracranial
response
|
Asymptomatic
(Cohort A; n = 101) |
Symptomatic
(Cohort B; n = 18) |
Best
overall response, n (%)
|
||
CR
|
29 (29)
|
2 (11)
|
PR
|
26 (26)
|
1 (5.6)
|
SD ≥6
mo
|
4 (4)
|
1 (5.6)
|
CBR, %
(95% CI)
|
58.4
(48.2–68.1)
|
22.2
(6.4–47.6)
|
While I am glad to note those responses, you would be hard pressed to convince me to go with ipi/nivo alone...given all we have learned about the positive response systemic therapy COMBINED with radiotherapy provides. You can read a zillion articles on the combo here:
Radiation for melanoma
I am not even going to try to note ALL the posts and discussions I have reported regarding the ipi/nivo combo! We have long known that the 15% response rate to ipi alone and the 40% average response rate to either anti-PD-1 product alone jumps to around 50+% with the ipi/nivo combo. Just put "ipi/nivo" in the search bar to read the history for yourself. Now, there's this:
Long-term follow-up of CA209-004: A phase I dose-escalation study of combined nivolumab (NIVO) and ipilimumab (IPI) in patients with advanced melanoma. 2019 ASCO. Akins, Kirkwood, Wolchok, ..., Postow, ...Sznol. J Clin Oncol 37, 2019.
Background: We previously
reported a 3-year overall survival (OS) rate of 63% with NIVO+IPI concurrent
therapy in the initial phase I dose-escalation study for the combination,
conducted in patients (pts) with advanced melanoma. Here, we report OS after 5
years of overall study follow-up and assess survival rates after stopping
treatment. Methods: Adults
with previously treated or untreated unresectable stage III or IV melanoma, and
ECOG performance status of 0 or 1, received NIVO + IPI Q3W × 4 as mg/kg in one
of the following cohorts: (1) NIVO 0.3 + IPI 3; (2) NIVO 1 + IPI 3; (2a) NIVO 3
+ IPI 1; (3) NIVO 3 + IPI 3; (8) NIVO 1 + IPI 3. Cohorts 1-3 received
maintenance with NIVO Q3W × 4, then NIVO + IPI Q12W × 8 at assigned doses;
cohort 8 received NIVO Q2W for up to 96 weeks. Patients were followed for the
primary endpoint of safety and the secondary endpoints of response and
progression-free survival for up to 2.5 years, then for the survival
exploratory endpoint for up to an additional 3 years, for a maximum study
participation of 5.5 years. Results: At
a median follow-up of 43.1 months in all cohorts (N = 94), the
4- and 4.5-year OS rates were both 57%. The 4-year OS rates
for pts with normal (n = 58) versus elevated LDH (n = 36) were 62% versus 49%; for pts with wild-type (n = 66) and mutant (n = 24) BRAF tumors, 4-year OS rates were
54% and 61%, respectively. Following the last dose of study
drug (for any reason), overall post-treatment 1-, 2-, and 3-year OS rates were
74%, 65%, and 56%, respectively; in pts who
discontinued due to study drug toxicity (n = 32), post-treatment 1-, 2-, and
3-year OS rates were 84%, 75%, and 65%, respectively,
and in pts who discontinued for disease progression (n = 30), these were 52%, 34%, and 24%, respectively. Conclusions: This updated analysis
from study CA209-004 showed favorable survival outcomes with NIVO+IPI, regardless
of BRAF or LDH status, and
provided evidence of long-term survival following discontinuation of treatment
in pts with advanced melanoma. Clinical trial information: NCT01024231
Yep. "...analysis from study CA209-004 showed favorable survival outcomes with NIVO+IPI, regardless of BRAF or LDH status, and provided evidence of long-term survival following discontinuation of treatment in pts with advanced melanoma." NOW! Let's make these numbers even better!!!
We are beautiful before, during, and after...
...the storm. ~ c
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