A Phase II Study of the Combination of Bevacizumab, Pertuzumab, and Octreotide LAR for Patients with Advanced Neuroendocrine Cancers

Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development. Thus, earlier endpoints are preferable, and the objective response rate (ORR) has been traditionally used as a surrogate endpoint in phase II trials for neuroendocrine tumors (NETs). However, the present study showed that the ORR was not significantly correlated with median progression-free survival (PFS). On the other hand, the 12-month PFS rate showed very strong correlation with median PFS and is considered a good alternate endpoint for screening phase II trials for NETs.

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“…A total of 22 phase II trials with ≥20 patients per arm were identified (4 randomized trials and 18 nonrandomized trials; Fig. ; Table ).…”

Section: Resultsmentioning

confidence: 99%

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors

et al. 2018

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“…A total of 20 trials (Ramanathan et al 2001, Kulke et al 2004, Arnold et al 2005, Sun et al 2005, Yao et al 2007, Dahan et al 2009, Rinke et al 2009, Pavel et al 2011, Raymond et al 2011, Chan et al 2012, Meyer et al 2014, Hobday et al 2015, Bendell et al 2016, Strosberg et al 2016 with ≥20 patients per-arm were identified (10 randomized trials and 10 non-randomized trials), as well as four update reports (Yao et al 2013, 2016b, Faivre et al 2016, Rinke et al 2017) ( Fig. 1 and Table 1).…”

Section: Selection Of Studiesmentioning

confidence: 99%

Progression-free survival as a surrogate endpoint in advanced neuroendocrine neoplasms

Imaoka

Sasaki

Takahashi

et al. 2017

Endocrine-Related Cancer

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In oncology clinical trials, overall survival (OS) is considered the gold standard outcome measure. In phase III trials for neuroendocrine neoplasms (NENs), however, progression-free survival (PFS) is more frequently used, as NENs are relatively rare and indolent neoplasms. But this surrogacy of PFS for OS has never been systematically validated. We, therefore, performed a literature-based analysis of phase II and III trials for NENs to evaluate the correlation between PFS and OS in NENs treated with medical treatment. We identified phase II and III clinical trials of medical treatment for advanced NENs based on a systematic electronic search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. A total of 20 trials were identified, and 2530 patients and 30 treatment arms were included in the analysis. There was a statistically significant relationship between PFS and OS ( , 0.587; 95% confidence interval, 0.249-0.925). Conversely, the objective response rate was not significantly correlated with OS. The results of subgroup analyses indicated that the correlation between PFS and OS was higher for study arms that prohibited concomitant therapy with somatostatin analogues than for those that permitted it. The results of the present analysis indicate that PFS is significantly correlated with OS, and suggest that PFS is an acceptable surrogate for OS in clinical trials for NENs.

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“…Combination of depot octreotide, bevacizumab, and pertuzumab, a monoclonal antibody inhibiting the dimerization of HER2 with other HER receptors, was evaluated in a phase II clinical trial in patients with advanced well-differentiated NETs and demonstrated an ORR of 16% and a median PFS of 8.2 months [112]. …”

Section: Molecular and Mutation Targeted Therapymentioning

confidence: 99%

Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

Neychev

Kebebew

2017

International Journal of Surgical Oncology

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Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

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A Phase II Study of the Combination of Bevacizumab, Pertuzumab, and Octreotide LAR for Patients with Advanced Neuroendocrine Cancers

Abstract: Bevacizumab, pertuzumab, and octreotide depot was well-tolerated with a 16% ORR. Results in the well-differentiated carcinoid tumors are thought provoking.

Cited by 14 publications

References 8 publications

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors

Alternate Endpoints for Phase II Trials in Advanced Neuroendocrine Tumors

Progression-free survival as a surrogate endpoint in advanced neuroendocrine neoplasms

Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

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