Helpt u ons aan 500 donateurs om kanker-actueel online te houden?

Raadpleeg ook onze literatuurlijsten van arts-bioloog drs. Engelbert Valstar

1 november 2018: Zie ook dit artikel: 

https://kanker-actueel.nl/olaparib-als-onderhoudsbehandeling-voor-brca-12-uitgezaaide-platinum-gevoelige-eierstokkanker-geeft-70-procent-minder-kans-op-overlijden-in-vergelijking-met-placebo.html

1 augustus 2018: Bron: The Lancet

Uit twee onafhankelijk van elkaar uitgevoerde studies blijken zowel olaparib en niraparib, twee zogeheten parpremmers, indien gegeven als onderhoudsbehandeling aan patiënten met gevorderde eierstokkanker die nog steeds gevoelig zijn voor op platinum gebaseerde chemo, de kwaliteit van leven niet aan te tasten. In tegendeel de kwaliteit van leven verbeterde parallel aan de verbetering van de overall overleving.

Beide studies waren placebo gecontroleerde gerandomiseerde studies en werden de effecten van toegevoegde parpremmers olaparib en niraparib op de kwaliteit van leven dus vergeleken met een placebo. Beide studies zijn gepubliceerd in The Lancet

Afbeeldingsresultaat voor images of parp inhibitors

Uit de  SOLO2/ENGOT Ov-21 studie met olaparib:

Deze analyse van de SOLO2 / ENGOT Ov-21 studie rapporteert de kwaliteit van leven bij eierstokkankerpatiënten met op platina gebaseerde chemo gevoelig recidief van gevorderde eierstokkanker die olaparib kregen versus placebo-onderhoud. Overall overlevingstijd zonder significante symptomen van toxiciteit en op kwaliteit van leven gecorrigeerde progressievrije overleving waren significant langer met olaparib versus placebo.

  • Deze analyse van het SOLO2 / ENGOT Ov-21-onderzoek toont de kwaliteit van leven bij patiënten met platinagevoelige recidiverende eierstokkanker die olaparib kregen als onderhoudsbehandeling versus placebo. Overall overlevingstijd zonder significante symptomen van toxiciteit en op kwaliteit van leven gecorrigeerde progressievrije overlevingstijd waren significant langer met olaparib in vergelijking met een placebo.

  • Olaparib werd niet geassocieerd met enig nadelig effect op de kwaliteit van leven, terwijl het de progressievrije overleving verbetert.

Uit de ENGOT-OV16/NOVA studie met niraparib:

Astrazeneca gaf een persbericht uit over de studie met olaparib (klik op de titel voor het persbericht):

AstraZeneca’s PARP Drug Is First to Help New Ovarian Cancer Patients

Over the past few years, a new class of drugs known as “PARP” inhibitors has begun to change how ovarian cancer is treated. Data released by AstraZeneca and partner Merck this morning, from a Phase 3 study of the drug olaparib (Lynparza), could continue the trend.

AstraZeneca (NYSE: AZN) and Merck (NYSE: MRK) said that olaparib succeeded in a study known as “SOLO-1.” The drug helped stop cancer from spreading longer than a placebo when used as a maintenance therapy for advanced ovarian cancer patients who had responded to chemotherapy. These patients all have a mutated BRCA gene, a known driver of ovarian cancers. About 15 percent of ovarian cancer diagnoses are tied to a BRCA mutation, according to the Dana-Farber Cancer Institute.

The two companies didn’t disclose the details of the study, so it’s unclear how significant the drug’s benefit was. They also said, without specifics, that the drug’s side effects were “consistent with previous trials.” AstraZeneca and Merck will dish details at a future medical meeting and begin discussions with regulators in the U.S. and Europe about possible approval.

Olaparib blocks an enzyme, PARP, that tumors use to repair DNA damage. After some initial clinical setbacks, three PARP blockers have won FDA approval since 2014: olaparib, Tesaro’s (NASDAQ: TSRO) niraparib (Zejula) and Clovis Oncology’s (NASDAQ: CLVS) rucaparib (Rubraca). Olaparib was first, approved for patients with certain forms of ovarian cancer and defective BRCA genes who have failed multiple chemo regimens. Rucaparib followed with a similar approval, while Tesaro’s was the first of the class to win approval for ovarian cancer patients but not require a companion diagnostic test for the BRCA mutation. (Olaparib and rucaparib have since followed, and olaparib has been approved for breast cancer patients with BRCA mutations as well.)

Hier de twee abstracten met referentielijst:

women who receive niraparib as maintenance treatment for recurrent ovarian cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo.

Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial

Summary

Background

Quality of life (QOL) has become an important complementary endpoint in cancer clinical studies alongside more traditional assessments (eg, tumour response, progression-free survival, overall survival). Niraparib maintenance treatment has been shown to significantly improve progression-free survival in patients with recurrent ovarian cancer. We aimed to assess whether the benefits of extending progression-free survival are offset by treatment-associated toxic effects that affect QOL.

Methods

The ENGOT-OV16/NOVA trial was a multicentre, double-blind, phase 3, randomised controlled trial done in 107 study sites in the USA, Canada, Europe, and Israel. Patients with recurrent ovarian cancer who were in response to their last platinum-based chemotherapy were randomly assigned (2:1) to receive either niraparib (300 mg once daily) as a maintenance treatment or placebo. Randomisation was stratified based on time to progression after the penultimate platinum-based regimen, previous use of bevacizumab, and best response (complete or partial) to the last platinum-based regimen with permuted-block randomisation (six in each block) using an interactive web response system. The trial enrolled two independent cohorts on the basis of germline BRCA (g BRCA) mutation status (determined by BRAC Analysis Testing, Myriad Genetics, Salt Lake City, UT, USA). The primary endpoint of the trial was progression-free survival, and has already been reported. In this study, we assessed patient-reported outcomes (PROs) in the intention-to-treat population using the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L). We collected PROs from trial entry every 8 weeks for the first 14 cycles and every 12 weeks thereafter. If a patient discontinued, we collected PROs at discontinuation and during a postprogression visit 8 weeks (plus or minus 2 weeks) later. We assessed the effect of haematological toxic effects on QOL with disutility analyses of the most common grade 3–4 adverse events (thrombocytopenia, anaemia, and neutropenia) using a mixed model with histology, region, previous treatment, age, planned treatment, and baseline score as covariates. This study is registered with ClinicalTrials.gov, number NCT01847274.

Findings

Between Aug 28, 2013, and June 1, 2015, 553 patients were enrolled and randomly assigned to receive niraparib (n=138 in the g BRCAmut cohort, n=234 in the non-g BRCAmut cohort) or placebo (n=65 in the g BRCAmut cohort, n=116 in the non-g BRCAmut cohort). The mean FOSI score at baseline was similar between the two groups (range between 25·0–25·6 in the two groups). Overall QOL scores remained stable during the treatment and preprogression period in the niraparib group; no significant differences were observed between the niraparib and placebo group, and preprogression EQ-5D-5L scores were similar between the two groups in both cohorts (0·838 [0·0097] in the niraparib group vs 0·834 [0·0173] in the placebo group in the g BRCAmut cohort; and 0·833 [0·0077] in the niraparib group vs 0·815 [0·0122] in the placebo group in the non-g BRCAmut cohort). The most common adverse events reported at screening (baseline) were lack of energy (425 [79%]; 97 [18%] reporting severe lack of energy), pain (236 [44%]), and nausea (118 [22%]). All symptoms, except nausea, either remained stable or improved over time in the niraparib group. The most common grade 3 or 4 toxicities observed in the niraparib group were haematological in nature: thrombocytopenia (124 [34%] of 367 patients), anaemia (93 [25%]), and neutropenia (72 [20%]); disutility analyses showed no significant QOL impairment associated with these toxic effects.

Interpretation

These PRO data suggest that women who receive niraparib as maintenance treatment for recurrent ovarian cancer after responding to platinum treatment are able to maintain QOL during their treatment when compared with placebo.

Funding

TESARO.

References

World Cancer Research Fund International
Ovarian cancer statistics.
American Cancer Society
Key statistics for ovarian cancer.
National Cancer Institute
Suveillance, Epidemiology, and End Results Program. Cancer stat facts: ovarian cancer.
  • Ledermann, JA
  • Raja, FA
  • Fotopoulou, C
  • et al.
Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Ann Oncol. 2013; 24: vi24-vi32
National Comprehensive Cancer Network
NCCN clinical practice guidelines in oncology. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer.
(Version 4.2017)
www.nccn.org
Date: Nov 9, 2017
Date accessed: December 1, 2017
  • Hanker, LC
  • Loibl, S
  • Burchardi, N
  • et al.
The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy.
Ann Oncol. 2012; 23: 2605-2612
  • McWhinney, SR
  • Goldberg, RM
  • McLeod, HL
Platinum neurotoxicity pharmacogenetics.
Mol Cancer Ther. 2009; 8: 10-16
  • Ferrell, B
  • Smith, SL
  • Cullinane, CA
  • Melancon, C
Psychological well being and quality of life in ovarian cancer survivors.
Cancer. 2003; 98: 1061-1071
  • Reb, AM
Transforming the death sentence: elements of hope in women with advanced ovarian cancer.
Oncol Nurs Forum. 2007; 34: E70-E81
  • Adamowicz, K
  • Saad, ED
Health related quality of life assessment in contemporary phase III trial in advances colorectal cancer.
Cancer Treat Rev. 2016; 50: 194-199
  • Bottemley, AB
  • Pe, M
  • Sloan, J
  • et al.
Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.
Lancet Oncol. 2016; 17: e510-E514
  • Vodicka, E
  • Kim, K
  • Devine, EB
  • Gnanasakthy, A
  • Scoggins, JF
  • Patrick, DL
Inclusion of patient-reported outcome measures in registered clinical trials: evidence from ClinicalTrials.gov (2007–2013).
Contemp Clin Trials. 2015; 43: 1-9
  • Joly, F
  • Hilpert, F
  • Okamoto, A
  • et al.
Fifth ovarian cancer consensus conference of the gynecologic cancer intergroup: recommendations on incorporating patient-reported outcomes in clinical trials in epithelial ovarian cancer.
Eur J Cancer. 2017; 78: 133-138
  • Stark, D
  • Nankivell, M
  • Pujade-Lauraine, E
  • et al.
Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial.
Lancet Oncol. 2013; 14: 236-243
  • Mirza, MR
  • Monk, BJ
  • Herrstedt, J
  • et al.
Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.
N Engl J Med. 2016; 375: 2154-2164
  • Beaumont, S
  • Yount, D
  • Lalla, D
  • et al.
Validation of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer.
Proc Am Soc Clin Oncol. 2007; 25 ((abstr 16021).): 663s ((abstr 16021).)
  • Herdman, M
  • Gudex, C
  • Lloyd, A
  • et al.
Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L).
Qual Life Res. 2011; 20: 1727-1736
  • Pickard, AS
  • Neary, MP
  • Cella, D
Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer.
Health Qual Life Outcomes. 2007; 5: 70
  • McClure, NS
  • Sayah, FA
  • Xie, F
  • Luo, N
  • Johnson, JA
Instrument-defined estimates of the minimally important difference for EQ-5D-5L index scores.
Value Health. 2017; 20: 644-650
  • Ledermann, JA
  • Harter, P
  • Gourley, C
  • et al.
Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer.
Br J Cancer. 2016; 115: 1313-1320
  • Coleman, RL
  • Oza, AM
  • Lorusso, D
  • et al.
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet. 2017; 390: 1949-1961

Olaparib was not associated with any detrimental effect on quality of life, while improving progression-free survival.

Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial

Summary

Background

In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 ( BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits.

Methods

In SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6–12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity and quality-adjusted progression-free survival ). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants.

Findings

The adjusted average mean change from baseline over the first 12 months in TOI was −2·90 (95% CI −4·13 to −1·67) with olaparib and −2·87 (–4·64 to −1·10) with placebo (estimated difference −0·03; 95% CI −2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98–8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70–8·96) were significantly longer with olaparib than with placebo.

Interpretation

Olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies.

Funding

AstraZeneca.

References

European Medicines Agency
Lynparza: summary of product characteristics.
FDA
Lynparza: highlights of prescribing information.
  • Pujade-Lauraine, E
  • Ledermann, JA
  • Selle, F
  • et al.
Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Oncol. 2017; 18: 1274-1284
  • Eisenhauer, EA
  • Therasse, P
  • Bogaerts, J
  • et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
Eur J Cancer. 2009; 45: 228-247
  • Wilson, MK
  • Pujade-Lauraine, E
  • Aoki, D
  • et al.
Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease.
Ann Oncol. 2017; 28: 727-732
  • Frank, L
  • Basch, E
  • Selby, JV
The PCORI perspective on patient-centered outcomes research.
JAMA. 2014; 312: 1513-1514
  • Minion, LE
  • Coleman, RL
  • Alvarez, RD
  • Herzog, TJ
Endpoints in clinical trials: what do patients consider important? A survey of the Ovarian Cancer National Alliance.
Gynecol Oncol. 2016; 140: 193-198
  • Havrilesky, LJ
  • Alvarez, SA
  • Ehrisman, JA
  • et al.
Patient preferences in advanced or recurrent ovarian cancer.
Cancer. 2014; 120: 3651-3659
AstraZeneca
Global policy: bioethics.
  • Basen-Engquist, K
  • Bodurka-Bevers, D
  • Fitzgerald, MA
  • et al.
Reliability and validity of the functional assessment of cancer therapy—ovarian.
J Clin Oncol. 2001; 19: 1809-1817
  • Oppe, M
  • Devlin, NJ
  • van Hout, B
  • Krabbe, PF
  • de Charro, F
A program of methodological research to arrive at the new international EQ-5D-5L valuation protocol.
Value Health. 2014; 17: 445-453
  • Ledermann, J
  • Harter, P
  • Gourley, C
  • et al.
Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.
N Engl J Med. 2012; 366: 1382-1392
  • Beaumont, JL
  • Salsman, JM
  • Diaz, J
  • et al.
Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma.
Cancer. 2016; 122: 1108-1115
  • Ledermann, J
  • Harter, P
  • Gourley, C
  • et al.
Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.
Lancet Oncol. 2014; 15: 852-861
  • Booth, CM
  • Eisenhauer, EA
Progression-free survival: meaningful or simply measurable?.
J Clin Oncol. 2012; 30: 1030-1033
  • Herzog, TJ
  • Armstrong, DK
  • Brady, MF
  • et al.
Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.
Gynecol Oncol. 2014; 132: 8-17
  • Diaby, V
  • Adunlin, G
  • Ali, AA
  • Tawk, R
Using quality-adjusted progression-free survival as an outcome measure to assess the benefits of cancer drugs in randomized-controlled trials: case of the BOLERO-2 trial.
Breast Cancer Res Treat. 2014; 146: 669-673
  • Gelber, RD
  • Goldhirsch, A
A new endpoint for the assessment of adjuvant therapy in postmenopausal women with operable breast cancer.
J Clin Oncol. 1986; 4: 1772-1779
  • Gelber, RD
  • Goldhirsch, A
  • Cavalli, F
Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer.
Ann Intern Med. 1991; 114: 621-628
  • Glasziou, PP
  • Cole, BF
  • Gelber, RD
  • Hilden, J
  • Simes, RJ
Quality adjusted survival analysis with repeated quality of life measures.
Stat Med. 1998; 17: 1215-1229
  • du Bois, A
  • Floquet, A
  • Kim, JW
  • et al.
Incorporation of pazopanib in maintenance therapy of ovarian cancer.
J Clin Oncol. 2014; 32: 3374-3382
  • Friedlander, M
  • Rau, J
  • Lee, CK
  • et al.
Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters-patient-centered end points in trials of maintenance therapy.
Ann Oncol. 2018; 29: 737-743

Plaats een reactie ...

Reageer op "Parpremmers Olaparib en niraparib gegeven als onderhoudsbehandeling bij gevorderde chemo gevoelige eierstokkanker heeft geen negatief effect op kwaliteit van leven en geeft wel betere overall overleving"


Gerelateerde artikelen
 

Gerelateerde artikelen

niraparib plus bevacizumab >> Olaparib als onderhoudsbehandeling >> Olaparib, een PARP remmer, >> Parpremmers Olaparib en niraparib >> Patienten met gevorderde eierstokkanker >> Parpremmer rucaparib verdubbelt >> Niraparib geeft zeer goede >> Olaparib plus cedinarib lijkt >> PARP remmers zoals olaparib >> BRCA - erfelijkheid: Combinatie >>