P1.07-015 STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC

Woll, Penella J.; Gaunt, Piers; Steele, N.; Ahmed, Samreen; Mulatero, C; Shah, Riyaz; Danson, Sarah; Hodgkinson, Elizabeth; James, K.; Watkins, Ben; Fletcher, Peter; Billingham, Lucinda

doi:10.1016/j.jtho.2016.11.926

Cited by 21 publications

(19 citation statements)

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“…In total, 1,957 patients from eight RCTs 7 – 9 , 17 – 21 were available for the meta-analysis, of whom 786 had ovarian cancer, 7 , 18 – 20 302 breast cancer, 9 649 gastric cancer, 8 , 17 and 220 small-cell lung cancer (SCLC). 21 Of the included studies, three were Phase III RCTs 7 – 9 and five were Phase II RCTs. 17 – 21 All studies reported sufficient data on PFS 7 – 9 , 17 – 21 and OS, 7 – 9 , 17 – 21 and six reported sufficient data on ORR.…”

Section: Resultsmentioning

confidence: 99%

“… 21 Of the included studies, three were Phase III RCTs 7 – 9 and five were Phase II RCTs. 17 – 21 All studies reported sufficient data on PFS 7 – 9 , 17 – 21 and OS, 7 – 9 , 17 – 21 and six reported sufficient data on ORR. 8 , 9 , 17 – 20 Additionally, five trials reported sufficient data on efficacy of olaparib in patients with BRCA mutations, 7 , 9 , 18 – 20 and two trials reported efficacy data in patients with ATM deficiency.…”

Section: Resultsmentioning

confidence: 99%

“… 8 , 17 Two schedules of olaparib oral tablets were investigated in the analysis conducted by Woll et al: 300 mg twice daily or 200 mg thrice daily. 21 Jadad scores are listed for each trial in Table 1 . The mean Jadad score was 4.4 (range 3–5), indicating that overall methodological quality of the included studies was generally good and fair.…”

Section: Resultsmentioning

confidence: 99%

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The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials

Guo¹,

Wu²,

Hong³

et al. 2018

CMAR

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PurposePARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients.MethodsPubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models.ResultsEight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47–0.82; P=0.001), OS (HR 0.82, 95% CI 0.73–0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16–1.65; P<0.001) when compared with therapy not containing olaparib. This association was further confirmed by sensitivity analysis. Additionally, olaparib treatment offered a significant survival benefit for patients with BRCA mutation. Moreover, treatment with olaparib was associated with a significant increase in risk of severe anemia.ConclusionOlaparib treatment has better treatment response compared with therapy not containing olaparib, whereas olaparib can increase the risk of severe anemia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials

Guo¹,

Wu²,

Hong³

et al. 2018

CMAR

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“…Single-agent olaparib was tested as maintenance therapy after completion of frontline chemotherapy in the Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence (STOMP) trial but did not show any clinical benefit in comparison with placebo. 30 The combination of olaparib and temozolomide, however, showed promising activity in relapsed SCLC, whereas the combination of veliparib and temozolomide showed efficacy only in subset of patients with relapsed SCLC who had with SLFN11 expression. 31,32 Although the initial result of our study is promising, additional confirmation in a larger definitive study is warranted, given the mixed results reported by other studies of PARP inhibitors in this patient population.…”

Section: Discussionmentioning

confidence: 97%

Randomized Phase II Trial of Cisplatin and Etoposide in Combination With Veliparib or Placebo for Extensive-Stage Small-Cell Lung Cancer: ECOG-ACRIN 2511 Study

Owonikoko

Dahlberg

Sica

et al. 2019

JCO

134

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Purpose Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). Materials and Methods Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m2 intravenously on day 1 and 100 mg/m2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. Results A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade ≥ 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. Conclusion The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.

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“…PARP inhibitors are also being investigated in the maintenance setting in patients with SCLC, who have not progressed after first line chemotherapy or chemoradiation. The phase 2 STOMP trial, showed no significant benefit of olaparib as a maintenance treatment compared to placebo [57]. In an ongoing phase 3 trial, niraparib is being compared to placebo as maintenance therapy in Chinese patients with ES-SCLC [58].…”

Section: Dna Damage Response Targetingmentioning

confidence: 99%

Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

Lum

Alamgeer

2019

Cancers

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Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.

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P1.07-015 STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC

Cited by 21 publications

References 0 publications

The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials

The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials

Randomized Phase II Trial of Cisplatin and Etoposide in Combination With Veliparib or Placebo for Extensive-Stage Small-Cell Lung Cancer: ECOG-ACRIN 2511 Study

Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

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