New patient-reported quality-of-life data from an exploratory endpoint in the pivotal phase 3 CheckMate -141 trial evaluating Nivolumab ( Opdivo ) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after Platinum therapy compared to investigator’s choice of therapy ( Methotrexate, Docetaxel or Cetuximab ) were presented.
Outcome assessments showed Nivolumab stabilized patients’symptoms and functioning, including physical, role and social functioning across three separate instruments.
Both PD-L1 expressors and non-expressors treated with investigator’s choice of therapy experienced statistically significant worsening of patient-reported outcomes from baseline to week 15 versus Nivolumab.
In addition, Nivolumab more than doubled the time to deterioration for most functional domains measured and significantly delayed the time to worsening symptoms of fatigue, dyspnea and insomnia, compared to investigator’s choice of therapy.
Squamous cell carcinoma of the head and neck accounts for approximately 90% of all head and neck cancers and may impact a patient’s physiological function ( e.g., breathing, swallowing, eating, drinking ), personal characteristics ( e.g., appearance, speaking, voice ), sensory function ( e.g., taste, smell, hearing ) as well as psychological and social functioning.
CheckMate -141 is a phase 3, open-label, randomized trial that evaluated Nivolumab versus investigator’s choice of therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck ( SCCHN ) with tumor progression within six months of Platinum therapy in the adjuvant, primary, recurrent or metastatic setting.
Patient-reported outcomes data were collected using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire ( EORTC QLQ-C30 ), EORTC Head and Neck Cancer-Specific Module ( EORTC QLQ-H&N35 ) and the 3-level EQ-5D questionnaire ( EQ-5D ).
The questionnaires were administered at baseline ( cycle 1, day 1 ), week 9 and at six-week intervals thereafter while patients were on treatment.
Clinical relevance was assessed using an established minimally important difference ( MID ) of greater than or equal to 10 points for EORTC subscales.
Both the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires showed there were significant differences in patient-reported outcomes between patients treated with Nivolumab and those treated with investigator’s choice of therapy at 15 weeks.
In the EORTC QLQ-C30, while patients treated with Nivolumab had stable patient-reported outcomes relative to baseline, those treated with investigator’s choice of therapy had significant and clinically meaningful worsening of physical, role and social functioning ( p less than 0.001 versus Nivolumab ), fatigue ( p less than 0.001 versus Nivolumab ), dyspnea ( p less than 0.001 versus Nivolumab ) and appetite loss ( p=0.004 versus Nivolumab ).
Nivolumab more than doubled the median time to deterioration for global health status ( 7.7 versus 3.0 months ), physical functioning ( 7.8 versus 3.6 months ), role functioning ( 8.6 versus 3.8 months ), cognitive functioning ( 7.8 versus 3.3 months ) and social functioning ( 7.7 versus 3.0 months ), compared with investigator’s choice of therapy.
In emotional functioning, Nivolumab demonstrated a median time to deterioration of 6.7 months versus 4.7 months for investigator’s choice of therapy.
Nivolumab also reduced the rate of clinically meaningful deterioration in fatigue, insomnia and dypsnea by 50% ( p=0.008 ).
Responses to the QLQ-H&N35 questionnaire showed while patients treated with Nivolumab reported stable patient-reported outcomes relative to baseline, those treated with investigator’s choice of therapy had significant worsening in pain ( p=0.022 versus Nivolumab ) as well as significant and clinically meaningful worsening in sensory problems ( p less than 0.001 versus Nivolumab ) and social contact problems ( p=0.001 versus Nivolumab ).
Compared with investigator’s choice of therapy, Nivolumab has reduced the rate of clinically meaningful deterioration in pain by 74% ( p less than 0.001 versus investigator’s choice of therapy ), sensory problems by 62% ( p=0.002 versus investigator’s choice of therapy ) and opening mouth problems by 51% ( p=0.029 versus investigator’s choice of therapy ).
Patients treated with Nivolumab experienced stable health status, as measured by the EQ-5D VAS, whereas those in the investigator’s choice arm experienced worsening of health status, with a statistically significant difference at 15 weeks ( p=0.037 ). Median time to deterioration of health status was nearly triple with 9.1 months for patients receiving Nivolumab versus 3.3 months for those in the investigator’s choice arm.
Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, nose and throat.
Head and neck cancer is the seventh most common cancer globally, with an estimated 600,000 new cases per year and 223,000-300,000 deaths per year.
The five-year survival rate is reported as less than 4% for metastatic stage IV disease. Risk factors for head and neck cancer include tobacco and alcohol consumption. The Human Papilloma Virus ( HPV ) infection also is a risk factor leading to rapid increase in oropharyngeal head and neck cancers in Europe and North America. ( Xagena )
Source: BMS, 2016