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4 februari 2016: Lees:  Minister Schippers heeft nivolumab voor gevorderde longkanker in het basispakket opgenomen per 1 maart 2016. 

10 mei 2015: Bron: Journal of Clinical Oncology

Nivolumab, een anti PD-medicijn (PD = programmed Death) zorgt voor spectaculaire resultaten bij zwaar voorbehandelde niet-kleincellige longkanker.  Aldus een fase I/II studie met totaal 126 patiënten met uitgezaaide vergevorderde niet-klein-cellige longkanker.

Overall overleving:

Mediane overall overleving voor alle gebruikte doses was 9.9 maanden, met 1-jaars, 2-jaars, en 3-jaars overleving van respectievelijk 42%, 24% en 18%. Let wel dit is een grope patiënten die in het eindstadium van hun ziekte verkeerden. Dat dan nog 18% de 3 jaar overleeft is wel heel bijzonder voor niet-klein-cellige longkanker. Onder de patiënten met plaveiselcarcinoom en niet-plaveisel carcinoom karakter was de mediane overall overleving respectievelijk 9.2 maanden en 10.1 maanden, met 1-jaars, 2-jaars, en 3-jaars overleving van 41%, 24%, en 19% en  42%, 27%, en 16% respectievelijk. Onder de 37 patiënten die de hoogste dosering van 3 mg/kg, hadden ontvangen bleek de 1-jaars, 2-jaars, en 3-jaars overeleving resepctievelijk 56%, 42%, en 27%. Dus bijna 1 op de 3 patiënten die de hoogste dosis nivolumab hadden ontvangen leefden nog na drie jaar. Dit is ongehoord voor deze groep van patiënten.

Nivolumab grafiek bij longkanker

Ik zal komende dagen de studieresultaten nog verder vertalen maar heb nu te weinig tijd daarvoor. Maar zie dit volledige studie rapport: Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer kunt u gratis inzien. 

Het abstract staat onderaan dit artikel maar hier de studieresultaten uit het originele studierapport..

Study Details

In the study, 129 patients with advanced NSCLC enrolled from 12 U.S. sites between November 2008 and January 2012 received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed (RECIST version 1.0) after each cycle. Patients had to have one to five prior systemic treatments for advanced NSCLC, progression on at least one platinum- or taxane-based regimen, and at least one measurable lesion.

Patients had a median age of 65 years (range = 38–85 years), 61% were male, 98% had Eastern Cooperative Oncology Group performance status of 0 or 1, and histology was nonsquamous in 58% and squamous in 42%. The number of prior systemic treatments was one or two in 46% and three or more in 54%; prior treatment included platinum-based therapy in 99%, tyrosine kinase inhibitors in 28%, surgery in 66%, radiotherapy in 58%, and hormonal, immunologic, or biologic therapy in 12%. EGFR mutation status was mutant in 9%, wild-type in 43%, and unknown in 47%; and KRAS mutation status was mutant in 16%, wild-type in 28%, and unknown in 56%.

Response Rates

Median follow-up was 39 months. Across all nivolumab dose levels, the objective response rate was 17.1% among all patients, including response rates of 16.7% in patients with squamous histology and 17.6% in those with nonsquamous histology. Response rates in patients receiving the 3-mg/kg dose selected for further development were 24.3% among all patients, including 22.2% in those with squamous histology and 26.3% in those with nonsquamous histology. Median duration of response among all responders was 17.0 months (range = 1.4+ to 36.8+ months), including median duration not reached in patients with squamous NSCLC, 14.2 months in those with nonsquamous histology, and 17.0 months in those receiving 3 mg/kg. 

Eleven (50%) of the 22 responses were documented at the first 8-week tumor assessment. Median progression-free survival in responders was 20.6 months (range = 4.7+ to 40.3+ months). Response was ongoing in 41% of responders at the time of analysis. Among 18 responders who discontinued nivolumab for reasons other than disease progression, 9 (50%) had responses of  over 9 months after the end of treatment. Stable disease of 24 weeks or more was observed in an additional 10% of patients.

Overall Survival

Median overall survival across all doses was 9.9 months, with 1-, 2-, and 3-year rates of 42%, 24%, and 18%. Among patients with squamous and nonsquamous histology, median overall survival was 9.2 months and 10.1 months, with 1-, 2-, and 3-year rates of 41%, 24%, and 19% and 42%, 27%, and 16%. Among 37 patients receiving 3 mg/kg, 1-, 2-, and 3-year survival rates were 56%, 42%, and 27%.

Immune-Pattern Responses

Unconventional immune-pattern responses—ie, persistent reduction in target lesions in the presence of new lesions or regression of target lesions after initial growth—were observed in an additional six patients (5%). Overall survival in these patients was 7.3, 11.2, 16.7, 26.7, 34.5+ (ongoing), and 54.3+ months at the time of analysis.

Toxicity

The most common treatment-related adverse events of any grade were fatigue (24%), decreased appetite (12%), and diarrhea (10%). Treatment-related grade 3 or 4 adverse events occurred in 14%, with fatigue (3%) being most common. Any-grade treatment-related adverse events of special interest included skin events in 15% of patients, gastrointestinal events in 12%, and pulmonary events in 7%. Grade ≥ 3 pneumonitis occurred in four patients (3%). Death considered related to treatment occurred in three patients (2%), in association with pneumonitis in each.

The investigators concluded: “Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.” Ongoing phase III trials include comparisons of nivolumab vs docetaxel in previously treated advanced squamous and advanced nonsquamous NSCLC and a comparison vs platinum-based therapy in previously untreated advanced PD-L1–positive disease.

Scott N. Gettinger, MD, of Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Bristol-Myers Squibb and Ono Pharmaceutical. For full disclosures of the study authors, visit jco.ascopubs.org.

Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.

Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer

  1. Julie R. Brahmer

+ Author Affiliations

  1. Scott N. Gettinger and Mario Sznol, Yale Cancer Center, New Haven, CT; Leora Horn, David P. Carbone, and Jeffrey A. Sosman, Vanderbilt University Medical Center; David R. Spigel, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Leena Gandhi, David M. Jackman, and F. Stephen Hodi, Dana-Farber Cancer Institute; Rebecca S. Heist and Lecia V. Sequist, Massachusetts General Hospital Cancer Center; David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Scott J. Antonia and Mary C. Pinder-Schenck, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Naiyer A. Rizvi, Richard D. Carvajal, and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; David C. Smith, University of Michigan, Ann Arbor, MI; Philip Leming, Christ Hospital Cancer Center, Cincinnati, OH; Suzanne L. Topalian, Drew M. Pardoll, and Julie R. Brahmer, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; and Vindira Sankar, Christoph M. Ahlers, Mark Salvati, Jon M. Wigginton, Georgia D. Kollia, and Ashok K. Gupta, Bristol-Myers Squibb, Princeton, NJ.
  1. Corresponding author: Scott N. Gettinger, MD, Yale Cancer Center, 333 Cedar St, FMP127, New Haven, CT 06520; e-mail: scott.gettinger@yale.edu.
  1. Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, May 31-June 4, 2013; the 15th World Conference on Lung Cancer, Sydney, New South Wales, Australia, October 27-30, 2013; the 50th ASCO Annual Meeting, Chicago, IL, May 30-June 3, 2014; and the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, October 30-November 1, 2014.

Abstract

Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non–small-cell lung cancer (NSCLC) receiving nivolumab in this trial.

Patients and Methods Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle.

Results Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis.

Conclusion Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.


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