Rachel Hodge

Kaplan–Meier estimates showing OS in all trial patients with a valid baseline (detectable or non-detectable) plasma ctDNA result in A, patients from the AURA3 trial (n = 291) and B, patients from the FLAURA trial (n = 499). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); HR, hazard ratio; mOS, median overall survival; NC, not calculable.

Kaplan–Meier estimates showing investigator-assessed PFS in FLAURA trial patients by clearance or non-clearance of plasma EGFRm status at Weeks 3 or 6 in patients who had baseline detectable plasma EGFRm. For comparison, patients with baseline non-detectable plasma EGFRm are included. A, Osimertinib arm by Week 3 plasma EGFRm status (n = 238). B, Comparator EGFR-TKI arm by Week 3 plasma EGFRm status (n = 243). C, Osimertinib arm by Week 6 plasma EGFRm status (n = 240). D, Comparator EGFR-TKI arm by Week 6 plasma EGFRm status (n = 235). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NC, not calculable; mPFS, median PFS; TKI, tyrosine kinase inhibitor.

Univariable and multivariable analyses for OS from the AURA3 trial (ctDNA evaluable population, n = 291) and FLAURA trial (ctDNA evaluable population, n = 499).

FLAURA flow diagram for ctDNA analysis (n = 499). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 3 patients in the osimertinib arm and 7 patients in the comparator EGFR-TKI arm without a valid ddPCR result at Weeks 3 and 6; these samples were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); TKI, tyrosine kinase inhibitor.

Assessment of correlation between EGFRm VAF in baseline plasma and investigator-assessed PFS in A, patients from the AURA3 trial, by treatment arm and B, patients from the FLAURA trial, by treatment arm. Abbreviations: CR, complete response; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NE, not evaluable; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; VAF, variant allelic fraction.

AURA3 flow diagram for ctDNA analysis (n = 291). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 9 patients in the osimertinib arm and 1 patient in the platinum-pemetrexed arm without a valid ddPCR result at Weeks 3 and 6; these samples were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R).

Correlation between EGFRm allelic fraction at baseline by ddPCR (Biodesix) and NGS (Guardant Health) analyses in A, patients from the AURA3 trial (n = 202) and B, patients from the FLAURA trial (n = 347). Abbreviations: ddPCR, droplet digital PCR; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NGS, next-generation sequencing.

Representativeness of study participants

Background: Progress on maternal health in low- and middle-income countries (LMICs) has stagnated, underscoring calls for holistic approaches to improve women’s nutrition. Diets link human health and environmental sustainability, necessitating equitable food system transformations to address climate change and malnutrition in all its forms. Food environments are a key entry point within food systems for improving nutrition; however, existing frameworks are not gender-sensitive and few consider vulnerable groups in low-resource settings. Methods: We conducted a systematic scoping review of peer-reviewed literature published in English, Spanish, Portuguese, and French from Web of Science, EBSCO, and PubMed to identify determinants of food acquisition practices and dietary intakes of women of reproductive age in LMICs. We synthesised 518 studies from 125 countries. By systematically identifying 143 eco-social, structural and individual-level determinants, we identified key determinants to develop an empirically grounded food environment conceptual framework for women. Findings: We identified women’s agency, characterised by decision-making and financial autonomy, bargaining power, control over time, and freedom of movement, as a prominent mediator of women’s food acquisition and dietary intakes, including across regions and the rural-urban continuum. Findings indicate that women’s agency, alongside supportive legislative, structural, and social enabling environments will be critical leverage points for improving women’s access to and consumption of nutritious foods, especially where resources are constrained. Conclusion: For countries to sustainably address malnutrition, this empirically grounded framework identifies pathways for addressing the macro, social and individual determinants of food acquisition and dietary intakes that are often overlooked yet critical for resilient food environments and sustainable development. Key messages: This is the first study to provide an empirically grounded food environment conceptual framework specific to women in LMICs. By systematically mapping key determinants of women’s food acquisition and dietary intakes, we identified novel food environment dimensions to develop an empirically grounded framework for women with applicability across regions and the rural-urban continuum in low- and middle-income countries. This novel conceptual framework, emphasising the importance of women’s agency in relation to external and personal food environments, may be used to guide research needs, analyses, and entry points for interventions to sustainably improve women’s nutrition in LMICs, especially in resource-constrained settings. Research in context: Evidence before this study: Women in low- and middle-income countries (LMICs) are disproportionally affected by malnutrition in all its forms. Food environments are a key food system entry point to improve nutrition. However, current food environment frameworks are not gender-sensitive, limiting the effectiveness of nutrition interventions. We systematically searched Web of Science Core Collection, EBSCO, and PubMed for peer-reviewed studies published between 1 ^st January 2010 and 30 ^th April 2023 in English, Spanish, Portuguese, and French reporting on determinants of women’s food acquisition practices and dietary intakes in LMICs. We used a broad search criterion based on emerging food environment concepts and the expanded food security definition. Data were extracted for women aged 15-49 years and by physiological status (pregnant, lactating, and non-pregnant/non-lactating). Added value of this study: This is the first study to provide an empirically grounded food environment conceptual framework specific to women in LMICs. By mapping patterns of 143 determinants inductively derived from the literature against existing conceptual frameworks, we identified novel determinants of women’s food acquisition and dietary intakes. Our results are representative across multiple geographical regions and the rural-urban continuum in LMICs. We add a novel socio-ecological layer: women’s agency as a key mediator for the ability of an individual to exert control over resources contributing to one’s own dietary outcomes. Implications of all the available evidence: Women’s food environments are complex, necessitating holistic systems approaches to sustainably improve women’s nutrition in LMICs. It is critical that policies and programmes address underlying legislative, structural and socio-cultural determinants mediating women’s agency, alongside other key external and personal food environment determinants influencing procurement and consumption of nutritious diets. This novel empirically grounded conceptual framework can guide future research priorities, analytical approaches, and key intervention points to optimise women’s nutrition.

Kaplan–Meier estimates showing investigator-assessed PFS in FLAURA trial patients by clearance or non-clearance of plasma EGFRm status at Weeks 3 or 6 in patients who had baseline detectable plasma EGFRm. For comparison, patients with baseline non-detectable plasma EGFRm are included. A, Osimertinib arm by Week 3 plasma EGFRm status (n = 238). B, Comparator EGFR-TKI arm by Week 3 plasma EGFRm status (n = 243). C, Osimertinib arm by Week 6 plasma EGFRm status (n = 240). D, Comparator EGFR-TKI arm by Week 6 plasma EGFRm status (n = 235). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NC, not calculable; mPFS, median PFS; TKI, tyrosine kinase inhibitor.