Longkanker: Immuuntherapie met Nivolumab + chemotherapie geeft op 3-jaars meting bij patienten met operabele niet-kleincellige longkanker (NSCLC) betere ziektevrije overleving (57 procent vs 43 procent) in vergelijking met alleen chemotherapie

13 april 2023: zie ook literatuurlijst voeding en voedingssuppletie en niet of weinig belastende behandelingen specifiek gerelateerd aan longkanker van arts-bioloog drs. Engelbert Valstar

13 april 2013: Bron: Journal of Thoracic Oncology (maart 2023)

Wanneer patiënten met operabele niet-kleincellige longkanker stadium IB - stadium IIIA vooraf aan een operatie (neoadjuvant) eerst immuuntherapie krijgen met het anti-PD medicijn Nivolumab naast de chemotherapie met een dubbele platina chemo (zie richtlijnen welke chemo wordt geadviseerd) dan verbetert de ziektevrije overleving op 3-jaars meting met 14 procent (57 procent verus 43 procent) in vergelijking met alleen chemotherapie. Daarnaast verbeterde ook de recidiefvrije overleving bij de patiënten die een operatie kregen. 28 procent van de patiënten die een operatie ondergingen en nivolumab plus chemotherapie kregen, kreeg een recidief vergeleken met 42 procent met alleen chemotherapie. Ook hier dus een verbetering met 14 procent ziektevrije overleving.

Dat blijkt uit de resultaten van de fase III Checkmate 816 studie en gepresenteerd op het European Lung Cancer Congress, gehouden van 29 maart tot 1 april in Kopenhagen, Denemarken.

Patrick Forde, M.B.B.Ch., van het Johns Hopkins Kimmel Cancer Center in Baltimore, en collega's voerden drie jaar durende werkzaamheids-, veiligheids- en verkennende biomarkeranalyses uit van de fase 3 CheckMate 816-studie, die aanvankelijk statistisch significante en klinisch relevante verbeteringen in ziektevrije overleving (EFS) liet zien met neoadjuvante nivolumab plus chemotherapie bij operabele niet-kleincellige longkanker (NSCLC).

Tot de patiënten behoorden volwassenen met stadium IB tot IIIA operabele niet-kleincellige longkanker (NSCLC) die willekeurig werden toegewezen aan een behandeling met 360 mg nivolumab plus chemotherapie of alleen chemotherapie om de drie weken gedurende drie cycli gevolgd door een operatie.

De onderzoekers vonden een aanhoudende ziektevrije overleving met nivolumab plus chemotherapie in vergelijking met alleen chemotherapie bij een mediane follow-up van 41,4 maanden (hazard ratio, 0,68).
Na drie jaar was de ziektevrije overleving (EFS) 57 procent met nivolumab plus chemotherapie versus 43 procent met alleen chemotherapie.
Ziektevrije overleving verbeterde verder met nivolumab plus chemotherapie bij patiënten die een operatie hadden ondergaan, ongeacht de chirurgische benadering of de omvang van de resectie.
Achtentwintig procent van de patiënten die een operatie ondergingen en nivolumab plus chemotherapie kregen, kreeg een recidief vergeleken met 42 procent met alleen chemotherapie.

Van de patiënten die nivolumab plus chemotherapie kregen, waren de BL 4-gen inflammatoire signatuurscores numeriek hoger bij patiënten met een gedeeltelijke of complete remissie (pCR) dan bij patiënten zonder. De onderzoekers rapporteerden graad 3 tot 4 behandelings- en operatiegerelateerde bijwerkingen bij respectievelijk 36 en 11 procent van de patiënten die nivolumab plus chemotherapie kregen. De overeenkomstige percentages in de groep die alleen chemotherapie kreeg waren 38 en 15 procent.

Het volledig studierapport is verkrijgbaar tegen betaling. Hier het abstract zoals gepresenteerd op het European Lung Cancer Congress.

84O - Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816

30 Mar 2023

Session

Proffered Paper 2

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Nicolas Girard

Citation

Journal of Thoracic Oncology (2023) rsion="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD

Authors

N. Girard1, J. Spicer2, M. Provencio3, S. Lu4, C. Wang5, M. Awad6, T. Mitsudomi7, E. Felip8, S.J. Swanson6, G. Saylors9, K. Chen10, F. TANAKA11, M.(. Tran12, N. Hu13, J. Cai12, J. Bushong12, J. Neely12, D. Balli12, S.R. Broderick14

Author affiliations

Resources

Abstract 84O

Background

The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816.

Methods

Adults with stage IB (tumors ≥4 cm)–IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples.

Results

At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68; 95% CI, 0.49–0.93); 3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3–4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm.

Table: 84O

N + C	C	N + C vs C
n	EFS	n	EFS	HR(95% CI)
Median(95% CI), mo	3-y rate, %	Median(95% CI), mo	3-y rate, %
All randomized pts	179	NR(31.6–NR)	57	179	21.1(14.8–42.1)	43	0.68(0.49–0.93)
Surgical approach
Minimally invasive	44	NR(30.8–NR)	67	29	NR(9.5–NR)	53	0.61(0.28–1.29)
Thoracotomy or conversion	105	NR(40.4–NR)	61	106	42.1(18.2–NR)	51	0.74(0.48–1.13)
Extent of resection
Lobectomy	115	NR(44.4–NR)	64	82	34.3(16.6–NR)	49	0.62(0.40–0.96)
Pneumonectomy	25	NR(19.4–NR)	67	34	21.1(13.9–NR)	48	NCa
Completeness of resection
R0	124	NR(44.4–NR)	64	105	42.1(19.6–NR)	51	0.65(0.43–0.98)
R1/R2	21	NR(12.6–NR)	53	25	NR(10.8–NR)	57	NCa

Too few events (< 10 per arm) to calculate HR.

NC, not calculated; NR, not reached.

Conclusions

Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR.

Clinical trial identification

NCT02998528.

Editorial acknowledgement

Medical writing and editorial support for the development of this abstract, under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface; Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron; Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation.

J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche; Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView; Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft; Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons.

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca.

M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda.

S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche.

M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax; Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly.

T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer; Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho; Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, Former president: IASLC.

E. Felip: Financial Interests, Institutional, Research Grant: Fundación Merck Salud, Merck KGAa; Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda; Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY; Non-Financial Interests, Personal, Member of the Board of Directors: Grífols.

S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon.

F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono; Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda.

P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb.

N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb.

J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb.

J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb.

J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb.

D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb.

S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca.

All other authors have declared no conflicts of interest.

niet-kleincellige longkanker, immuuntherpaie, anti-PD medicijnen, nivolumab, chemotherapie, ziektevrije overleving, fase III CheckMate 816 studie