Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial

Morgan, Robert D.; McNeish, Iain A.; Cook, Adrian; James, Elizabeth C.; Lord, Rosemary; Dark, Graham; Glasspool, Rosalind; Krell, Jonathan; Parkinson, Christine; Poole, Christopher; Hall, Marcia; Gallardo‐Rincón, Dolores; Lockley, Michelle; Essapen, Sharadah; Summers, James L.; Anand, Anjana; Zachariah, Abel; Williams, Sarah; Jones, Robin L.; Scatchard, Kate; Walther, Axel; Kim, Jae Weon; Sundar, Sudha; Jayson, Gordon C.; Ledermann, Jonathan A.; Clamp, Andrew R.

doi:10.1016/s1470-2045(20)30591-x

Cited by 40 publications

(25 citation statements)

References 30 publications

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“…Conflicting outcomes were reported about the predictive value of the radiological response regarding the probability of complete IDS, or patient prognosis [46,47]. A recent analysis of the ICON-8 phase III trial dataset on 1566 patients confirmed that the radiological response assessed with the Response Evaluation Criteria in Solid Tumors (RECIST) was not an appropriate parameter to assess the efficacy of the neoadjuvant chemotherapy and predict the benefit from IDS [48].…”

Section: Indicators Of Tumor Primary Chemosensitivitymentioning

confidence: 99%

“…The Gynecologic Cancer Intergroup (GCIG) defined the CA-125 response as a 50% reduction in CA-125 levels maintained for at least 28 days, in patients treated for recurrent diseases [49,50]. Different studies, including a recent analysis of the ICON-8 phase III trial dataset showed that this criterion was inadequate for assessing the efficacy of the neoadjuvant chemotherapy and predicting the benefit from IDS [48,51,52].…”

Section: Indicators Of Tumor Primary Chemosensitivitymentioning

confidence: 99%

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The role of the tumor primary chemosensitivity relative to the success of the medical-surgical management in patients with advanced ovarian carcinomas

You

González-Martín

Lheureux

et al. 2021

Cancer Treatment Reviews

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In patients with advanced ovarian carcinomas, the first-line treatment has historically relied on debulking surgery and platinum-based chemotherapy. If the major therapeutic/prognostic role of the surgery part is well understood, and integrated in disease-management algorithms, the impact of chemotherapy efficacy has been insufficiently addressed.This review describes the main indicators of the chemosensitivity reported in the literature (pathological response score & biomarkers; genomic alterations; DNA scars; imaging; and circulating tumor markers), and investigates the respective roles of the debulking surgery and tumor primary chemosensitivity relative to the success of the comprehensive medical-surgical treatment. The tumor primary chemosensitivity exhibits a major independent prognostic impact on the feasibility of complete interval debulking surgery after neoadjuvant chemotherapy, risk of subsequent platinum-resistant relapse, efficacy of subsequent maintenance therapies with bevacizumab or PARP inhibitors, progression-free survival, overall and long-term survival. While both the completeness of the surgery and the tumor primary chemosensitivity are undoubtedly major prognostic factors, the impact of the surgery may differ according to the primary chemosensitivity. This assumption raises a potential new concept: in patients with advanced ovarian carcinomas, the maximum tumor debulking should ideally be both biological (induced by systemic treatments) and physical (induced by surgery) for maximizing patient survival. Besides BRCA and HRD biomarkers, future trials and algorithms may integrate indicator(s) of the tumor primary chemosensitivity for guiding more subtly the surgical and medical management in first-line setting. Moreover, such a parameter would help in the development of novel approaches meant to reverse the resistance to chemotherapy and PARP inhibitors.

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Section: Indicators Of Tumor Primary Chemosensitivitymentioning

confidence: 99%

Section: Indicators Of Tumor Primary Chemosensitivitymentioning

confidence: 99%

The role of the tumor primary chemosensitivity relative to the success of the medical-surgical management in patients with advanced ovarian carcinomas

You

González-Martín

Lheureux

et al. 2021

Cancer Treatment Reviews

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“…More recently, Morgan et al reported the lack of accuracy of the GCIG criterion to identify the patients who were likely to benefit from interval debulking surgery (IDS) after neoadjuvant chemotherapy for EOC in the first-line setting of the phase III ICON-8 trial [ 14 , 20 ]. For example, a complete cytoreduction was achieved in 30 of 101 women (30%) without a GCIG CA-125 response and in 290 of 576 women (50%) who experienced a GCIG CA-125 response.…”

Section: Limitations Of the Gcig Ca-125 Response Definitionmentioning

confidence: 99%

“…The Gynecologic Cancer InterGroup (GCIG) defined the CA-125 response as a 50% reduction in CA-125 levels maintained for at least 28 days, in patients treated for recurrent disease [ 13 ]. However, the relevance of the GCIC criteria was recently questioned in the analyses of the CALYPSO trial in the recurrent setting and of ICON-8 trial in a first-line setting [ 10 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review

Lauby

Colomban

Corbaux

et al. 2021

Cancers

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Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III–IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.

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“…Chemotherapy is a standard first‐line therapy for various types of cancer 1–3 . However, chemotherapeutic agents, such as oxaliplatin, paclitaxel and vincristine, are neurotoxic 4–6 .…”

Section: Introductionmentioning

confidence: 99%

Analgesic effects of medicinal plants and phytochemicals on chemotherapy‐induced neuropathic pain through glial modulation

Lee

Kim

Park

et al. 2021

Pharmacology Res & Perspec

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Chemotherapy‐induced peripheral neuropathy (CIPN) frequently occurs in cancer patients. This side effect lowers the quality of life of patients and may cause the patients to abandon chemotherapy. Several medications (e.g., duloxetine and gabapentin) are recommended as remedies to treat CIPN; however, usage of these drugs is limited because of low efficacy or side effects such as dizziness, nausea, somnolence, and vomiting. From ancient East Asia, the decoction of medicinal herbal formulas or single herbs have been used to treat pain and could serve as alternative therapeutic option. Recently, the analgesic potency of medicinal plants and their phytochemicals on CIPN has been reported, and a majority of their effects have been shown to be mediated by glial modulation. In this review, we summarize the analgesic efficacy of medicinal plants and their phytochemicals, and discuss their possible mechanisms focusing on glial modulation in animal studies.

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Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial

Abstract: Arm 2 (n=263) Arm 3 (n=259) Total (n=779) Age, years 65 (59-70) 62 (54-68) 64 (55-69) 64 (56-69) ECOG performance status 0 105 (41) 113 (43) 93 (36) 311 (40)

Cited by 40 publications

References 30 publications

The role of the tumor primary chemosensitivity relative to the success of the medical-surgical management in patients with advanced ovarian carcinomas

The role of the tumor primary chemosensitivity relative to the success of the medical-surgical management in patients with advanced ovarian carcinomas

The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review

Analgesic effects of medicinal plants and phytochemicals on chemotherapy‐induced neuropathic pain through glial modulation

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