16 januari 2018: Lees ook dit artikel

https://kanker-actueel.nl/bepaalde-darmbacterien-kunnen-de-effectiviteit-van-immunotherapie-met-anti-pd-medicijnen-verhogen-bij-de-behandeling-van-melanomen.html

12 mei 2016: lees ook dit artikel:

https://kanker-actueel.nl/NL/immuuntherapeutische-behandelingen-met-ipilimumab-en-nivolumab-gelijktijdig-gegeven-geeft-spectaculaire-resultaten-80-procent-tumorreductie-bij-melanoompatienten-met-uitgezaaide-vergevorderde-vooraf-intensief-behandelde-ziekte.html

12 mei 2016: 34% van de mensen waarbij nivolumab in eerste instantie aansloeg overleeft de 5 jaar. Zelfs bij de 5 patienten die een recidief kregen na een eerste behandeling met nivolumab en daarmee waren gestopt kwamen opnieuw in een remissie en blijven dat tot aan de 5 jaar. Volgens de onderzoekers betekent het dat wie 5 jaar overleeft met alleen nivolumab zichzelf als genezen kan beschouwen. En dan te bedenken dat deze groep van patienten zwaar voorbehandeld was voordat ze aan nivolumab begonnen.

F. Stephen Hodi, MD

“Based on this analysis, survival appears to plateau at around 48 months and then stays durable. If you make it to 48 months, your chances of survival are excellent. This represents the longest survival follow-up of patients who received anti–PD-1 [programmed cell death protein 1] therapy in a clinical trial, and long-term survival is durable,” said lead author F. Stephen Hodi, MD, of Dana-Farber Cancer Center and Ludwig Center at Harvard, Boston.

Wat zal er gebeuren bj patienten die nog nooit zijn behandeld en direct immuuntherapie met nivolumab krijgen?

Kernpunten uit de Fase 1 studie

Immuuntherapie voor Advanced Melanoma

1/3 van de patienten met gevorderde melanomen en behandeld met nivolumab waren 5 jaar na de start van de behandeling nog in leven.
Deze patiënten waren zwaar voorbehandeld met een verwachte medinae overleving van 11 maanden.
5 patiënten stopten tijdens de studieduur met de behandeling in eerste instantie, kregen daarna een recidief en begonnen opnieuw met nivolumab. En kwamen opnieuw in een remissie.
Deze resultaten bevestigen dat nivolumab duurzame remissies kan bewerkstelligen en bij kan dragen aan overleving.

Overall overleving cijfers
	NIVO 3 mg/kg (n=17)	All Patients (N=107)
OS rate, % (95% CI)*
12-month	64.7 (37.7-82.3)	62.7 (52.6-71.2)
24-month	47.1 (23.0-68.0)	48.0 (38.1-57.2)
36-month	41.2 (18.6-62.6)	42.1 (32.4-51.4)
48-month	35.3 (14.5-57.0)	34.8 (25.7-44.1)
60-month	35.3 (14.5-57.0)	33.6 (24.6-42.9)
Median OS, months (95% CI)	20.3 (7.2-NR)	17.3 (12.5-37.8)
*Based on Kaplan-Meier estimates. NR, not reached.

Het abstract van de studie is gepresenteerd op ASCO 2016: klik op de volgende link of zie onderaan artikel.

Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial

Lees ook dit artikel:

This analysis represents the longest survival follow-up of pts who received anti-PD-1 therapy in a clinical study. In this heavily pretreated population of Melanome patients, these results suggest durable, long-term survival following NIVO monotherapy, with 34% of patients alive at 5 years.

Source: ASCO 2016

Abstract Number:

CT001

Presentation Title:

Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial

Presentation Time:

Sunday, Apr 17, 2016, 3:45 PM - 4:05 PM

Location:

La Nouvelle Orleans Ballroom, Morial Convention Center

Webcast Status:

Webcast Status Unknown

Author Block:

F. Stephen Hodi¹, Harriet Kluger², Mario Sznol², Richard Carvajal³, Donald Lawrence⁴, Michael Atkins⁵, John Powderly⁶, William Sharfman⁷, Igor Puzanov⁸, David Smith⁹, Philip Leming¹⁰, Evan Lipson⁷, Janis Taube⁷, Robert Anders⁷, Christine Horak¹¹, Joel Jiang¹¹, David McDermott¹², Jeffrey Sosman⁸, Julie Brahmer⁷, Drew Pardoll⁷, Suzanne Topalian⁷. ¹Dana-Farber Cancer Institute, Boston, MA; ²Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; ³Columbia University Medical Center, New York, NY; ⁴Massachusetts General Hospital Cancer Center, Boston, MA; ⁵Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; ⁶Carolina BioOncology Institute, Huntersville, NC; ⁷The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; ⁸Vanderbilt University Medical Center, Nashville, TN; ⁹University of Michigan, Ann Arbor, MI; ¹⁰The Christ Hospital Cancer Center, Cincinnati, OH; ¹¹Bristol-Myers Squibb, Princeton, NJ; ¹²Beth Israel Deaconess Medical Center, Boston, MA

Abstract Body:

Background: In previously treated MEL patients (pts), the results of an early phase I trial with NIVO monotherapy (CA209-003) demonstrated tumor responses that were durable even after treatment discontinuation (Topalian et al. J Clin Oncol 2014;32:1020). We report extended follow-up with 5-year overall survival (OS) data from this study.

Methods: IPI-naïve pts (N=107) who had received 1-5 prior systemic therapies for MEL were treated with NIVO (0.1, 0.3, 1, 3, or 10 mg/kg) every 2 weeks for ≤96 weeks. Pts were followed for OS, progression-free survival (PFS), long-term safety, and response duration after discontinuing NIVO treatment. Pts began treatment in October 2008, and current data were analyzed in October 2015 with a minimum follow-up of 45 months (time from when the last pt received his or her first dose of NIVO).

Results: Median age of the pts was 61 years, 67% were male, 97% had an ECOG performance status of 0 or 1, 62% had received ≥2 prior systemic therapies, and 36% had elevated lactate dehydrogenase levels at baseline. In all 107 pts, the 60-month OS rate was 34% (95% confidence interval : 25-43) and median OS was 17.3 months (95% CI: 12.5-37.8) (Table). OS rates appeared to plateau at ~48 months, although further follow-up is needed. Similar results were observed with NIVO at 3 mg/kg, the currently approved monotherapy dose (Table). At the last timepoint for tumor assessment, PFS rates at 30 months were 18.6% and 25.7% for all pts and those who received NIVO at 3 mg/kg, respectively.

Conclusions: This analysis represents the longest survival follow-up of pts who received anti-PD-1 therapy in a clinical study. In this heavily pretreated population of MEL pts, these results suggest durable, long-term survival following NIVO monotherapy, with 34% of pts alive at 5 years. Characteristics of long-term survivors and updated safety data will also be presented.

OS rates
	NIVO 3 mg/kg (n=17)	All Patients (N=107)
OS rate, % (95% CI)*
12-month	64.7 (37.7-82.3)	62.7 (52.6-71.2)
24-month	47.1 (23.0-68.0)	48.0 (38.1-57.2)
36-month	41.2 (18.6-62.6)	42.1 (32.4-51.4)
48-month	35.3 (14.5-57.0)	34.8 (25.7-44.1)
60-month	35.3 (14.5-57.0)	33.6 (24.6-42.9)
Median OS, months (95% CI)	20.3 (7.2-NR)	17.3 (12.5-37.8)
*Based on Kaplan-Meier estimates. NR, not reached.