PREDICTING EARLY TREATMENT DISCONTINUATION AND EFFECTIVENESS IN BEVACIZUMAB-TREATED PATIENTS WITH PRIMARY ADANCED OVARIAN CANCER: EXPLORATORY ANALYSES OF THE OTILIA STUDY (ON BEHALF OF NOGGO)

ObjectivePARADIGMS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study.MethodsPatients with multiple sclerosis (MS) (aged 10–<18 years) were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) in this flexible duration study. MRI was performed at baseline and every 6 months for up to 2 years or end of the study (EOS) in case of early treatment discontinuation/completion. Key MRI endpoints included the annualised rate of formation of new/newly enlarging T2 lesions, gadolinium-enhancing (Gd+) T1 lesions, new T1 hypointense lesions and combined unique active (CUA) lesions (6 months onward), changes in T2 and Gd+ T1 lesion volumes and annualised rate of brain atrophy (ARBA).ResultsOf the randomised patients, 107 each were treated with fingolimod and IFN β-1a for up to 2 years. Fingolimod reduced the annualised rate of formation of new/newly enlarging T2 lesions (52.6%, p<0.001), number of Gd+ T1 lesions per scan (66.0%, p<0.001), annualised rate of new T1 hypointense lesions (62.8%, p<0.001) and CUA lesions per scan (60.7%, p<0.001) versus IFN β-1a at EOS. The percent increases from baseline in T2 (18.4% vs 32.4%, p<0.001) and Gd+ T1 (–72.3% vs 4.9%, p=0.001) lesion volumes and ARBA (–0.48% vs −0.80%, p=0.014) were lower with fingolimod versus IFN β-1a, the latter partially due to accelerated atrophy in the IFN β-1a group.ConclusionFingolimod significantly reduced MRI activity and ARBA for up to 2 years versus IFN β-1a in PoMS.

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Discontinuation of poly(adenosine diphosphate-ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.34_suppl.118 ◽

2018 ◽

Vol 36 (34_suppl) ◽

pp. 118-118

Author(s):

Kyaw Zin Thein ◽

Anita Sultan ◽

Myo Zaw ◽

Sriman Swarup ◽

Myat M. Han ◽

...

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Dose Reduction ◽

Meta Analysis ◽

Adenosine Diphosphate ◽

Recurrent Ovarian Cancer ◽

Treatment Interruption ◽

Parp Inhibitors ◽

Treatment Discontinuation ◽

Phase Iii

118 Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total of 1,401 patients with recurrent ovarian cancer were eligible. The study arm used olaparib or niraparib or rucaparib while the control arm utilized placebo. The randomization ratio was 2:1 in all studies. The incidence of treatment interruption due to adverse events was 578 (61.8%) in study group versus 46 (9.8%) in control arm. The relative risk for treatment interruption was statistically significant at 5.87 (95% CI: 2.24 – 15.36, P < 0.001). The reduction in dose was reported in 496 (53.1%) in PARP inhibitors arm versus 37 (7.9%) in control group. The pooled RR for dose reduction was 7.49 (95% CI: 3.44 – 16.29, P < 0.001). The treatment discontinuation rate was 11.4% higher with PARP inhibitors than with control arm (RR - 6.84; 95% CI: 3.51 – 13.34, P < 0.001). Conclusions: Our study showed that patients on PARP inhibitors experienced some adverse events which led to significant drop outs although the definitive advantage to PARP inhibitors is still shown in the studies. Preemptive measures with proper supportive care will aide in reducing those toxicities, improve patients’ quality of life and may probably affect patients’ compliance.

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Predictive value of bother by side effects of treatment prior to protocol therapy for early treatment discontinuation in clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19132 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19132-e19132

Author(s):

Fengmin Zhao ◽

John Peipert ◽

Ju-Whei Lee ◽

Fangxin Hong ◽

Edward Ip ◽

...

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Early Treatment ◽

Predictive Value ◽

Previous Treatment ◽

Treatment Phase ◽

Treatment Discontinuation ◽

Phase Iii ◽

Phase Iii Clinical Trials ◽

Treatment Naïve

e19132 Background: The Functional Assessment of Cancer Therapy–General has an item about patient tolerability of treatment: “I am bothered by side effects of treatment” (GP5). We examined the predictive value of this single item for early treatment discontinuation in clinical trials. Methods: GP5 level prior to protocol therapy (rated using a 5-point Likert scale) and treatment start/end dates and off treatment reason data at each treatment phase were drawn from five phase III clinical trials conducted by ECOG-ACRIN. In the present analysis, GP5 was dichotomized as 0 = “Not at all”/“A little bit” and 1 = “Somewhat”/“Quite a bit”/“Very Much”. Early treatment discontinuation was defined either as receiving less than protocol specified cycles of treatment when maximum cycles specified in the protocol (E1A06 induction, E1912 induction, E1609 induction, E1105 induction, E5103 adjuvant), analyzed using logistic regression via odds ratio [OR]), or treatment cessation for reasons other than progressive disease or death when treatment continued until progression or intolerability (E1A06 maintenance, E1912 maintenance, E1609 maintenance, E1105 maintenance), analyzed using Cox proportional hazard model via hazard ratio [HR]. Results: GP5 prior to treatment was significantly associated with early discontinuation of E1A06 maintenance, E1609 maintenance, E1912 maintenance, and E1912 induction. No significant association was found for other therapies examined in the study. Conclusions: High GP5 level prior to treatment is associated with higher likelihood of early treatment discontinuation in patients who have received previous treatment. The limited predictive value of GP5 for treatment naïve patients is more limited, serial on-treatment assessment should be considered in this setting. Clinical trial information: NCT00602641 . [Table: see text]

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