Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab

Abstract

In a randomised phase 3 trial, panitumumab significantly improved progression-free survival (PFS) in patients with refractory metastatic colorectal cancer (mCRC). This analysis characterises the association of PFS with CRC symptoms, health-related quality of life (HRQoL), and overall survival (OS). CRC symptoms (NCCN/FACT CRC symptom index, FCSI) and HRQoL (EQ-5D) were assessed for 207 panitumumab patients and 184 best supportive care (BSC) patients who had at least one post-baseline patientreported outcome (PRO) assessment. Patients alive at week 8 were included in the PRO and OS analyses and categorised by their week 8 progression status as follows: no progressive disease (no PD; best response of at least stable disease) vs progressive disease (PD). Standard imputation methods were used to assign missing values. Significantly more patients were progression free at weeks 8 -24 with panitumumab vs BSC. After excluding responders, a significant difference in PFS remained favouring panitumumab (HR ¼ 0.63, 95% CI ¼ 0.52 -0.77; Po0.0001). At week 8, lack of disease progression was associated with significantly and clinically meaningful lower CRC symptomatology for both treatment groups and higher HRQoL for panitumumab patients only. Overall survival favoured no PD patients vs PD patients alive at week 8. Lack of disease progression was associated with better symptom control, HRQoL, and OS.

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

“…Panitumumab, a fully human IgG2κ monoclonal antibody, was recently approved in the US and Europe as third-line treatment of metastatic colorectal cancer [12,24]. Both antibodies have been shown to reduce the risk of tumor progression and to improve overall survival (OS), progression-free survival (PFS) and quality of life in patients with refractory colorectal cancer [11,23,[25][26][27][28]. However, only a small proportion (8-23%) of patients were observed to achieve an objective response with cetuximab [11,23,25] or panitumumab [26,28].…”

“…Cetuximab has shown efficacy in some patients with tumors negative for EGFR as assessed by IHC [32], while many patients with EGFR-expressing colorectal tumors fail to respond to cetuximab [11,25]. Similarly, a number of patients with EGFR-expressing tumors do not benefit from panitumumab therapy [26][27][28]. More recently, increased EGFR gene copy number as detected by fluorescence in situ hybridization (FISH) was associated with response to cetuximab or panitumumab [33].…”

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial

“…Это особенно актуально для новых методов лечения, выступающих в качестве дополнений к существующим химиотерапевти-ческим режимам лечения, когда зачастую сложно пока-зать преимущество КЖ по сравнению только с химиоте-рапией или когда преимущества ОВ не отображены. Связь между ВБП и КЖ подтверждает использование ВБП в качестве первичной конечной точки клинических исследований у пациентов с НМРЛ и доказывает цен-ность ВБП как конечной точки, связанной с ощутимыми изменениями [10,11,13,14,21].…”

“…Оценка связи между КЖ и ответом опухоли на лечение у больных онкологическими заболеваниями разной локали-зации, например раком молочной железы и почечно-кле-точным раком, изучалась в ряде клинических исследований [23,21,19,20,7]. Было показано, что у пациентов с медлен-ным прогрессированием опухолевого заболевания, продол-жающих лечение, КЖ стабильное или снижается медленнее, чем у пациентов с быстрым прогрессированием.…”

Benefits, Issues, and Recommendations for Personalized Medicine in Oncology in Canada

“…In combination with BRAF genotyping, vemurafenib represents a major advance in melanoma treatment. It is effective in reducing tumour size by up to 50%, and it extends progression-free survival in 40%-60% of patients who have tumours that harbour the V600E BRAF mutation 23 . Another example is the identification of activating mutations or translocations in the ALK (anaplastic lymphoma kinase) gene.…”