Total Health · Personalized Comprehensive Review

The items below decide guideline branches and trial cohorts. Until they are confirmed, every trial match in this review is conditional and every molecular idea is a hypothesis, not a recommendation.

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You are a 62-year-old never-smoker living with metastatic lung adenocarcinoma driven by an EGFR exon 19 deletion. Osimertinib controlled the cancer for several years, including through two limited areas of progression that were treated locally.

The cancer is now growing more broadly in the liver and bones. A May 2026 liver biopsy still showed adenocarcinoma, with no small-cell transformation. Tissue testing reported an acquired MET amplification, a finding that can help explain resistance to EGFR-directed therapy.

There is an important uncertainty: the MET signal was clear in tissue but only low-level or indeterminate in blood. Because that distinction may influence which treatments or trials are reasonable, the report places confirmation of MET status at the top of the next-step list.

You remain active and independent with an ECOG performance status of 1. Mild fatigue and right upper-quadrant discomfort are present, while kidney function and blood counts remain broadly preserved. Maintaining function and quality of life is a central decision factor.

The current decision point is progression after long-term osimertinib, with a new tissue MET-amplification signal and a need to compare guideline-supported care, biomarker-directed strategies, and credible trials.

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1. What changed after several years of benefit from osimertinib?
2. How confident should we be that MET amplification is driving the current progression?
3. What guideline-supported paths belong in the discussion now?
4. Which biomarker-directed or investigational strategies are plausible, and what must be verified first?
5. How should daily function, symptoms, geography, and quality-of-life goals shape the choice?

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How your cancer is changing. The original EGFR exon 19 driver remains detectable, which means the cancer still carries the biology that made osimertinib effective.

Progression biopsy report (12 May 2026): "metastatic adenocarcinoma compatible with lung primary; no small cell transformation identified"

Tissue molecular report (20 May 2026): "MET amplification detected; EGFR exon 19 deletion persistent; no EGFR C797S detected" The new MET amplification is a possible acquired resistance mechanism: a second growth signal may now be helping tumour cells bypass EGFR blockade. The absence of EGFR C797S and the liver biopsy's continued adenocarcinoma appearance narrow, but do not eliminate, the range of possible resistance mechanisms. The report therefore treats MET as a strong lead that still deserves careful confirmation.

The factors shaping your treatment options

Your treatment response so far. Osimertinib delivered meaningful, durable control beginning in May 2022. Continuing it through isolated progression while using local radiation was coherent with the disease pattern at those earlier decision points. The April to July 2026 imaging pattern is different: progression is now systemic, so the next conversation must address a new systemic strategy.

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The review does not select a single regimen. It organises three decision pathways for the treating team to compare after the MET result is clarified.

Current decision · Guideline-supported systemic care

In Jane's case: a standard post-osimertinib systemic pathway can be discussed now while the molecular finding is reviewed. The exact regimen belongs to the treating oncologist.

Why it belongs in the conversation. Systemic progression in the liver and bone means that local therapy alone is unlikely to address the full disease burden. Established post-progression care provides the clearest benchmark against which more specialised options should be compared.

What should shape the choice

• Current ECOG 1 function and the goal of maintaining independence.
• Mildly rising liver enzymes and alkaline phosphatase in the setting of liver progression.
• Prior treatment tolerance, expected toxicity, travel burden, and treatment schedule.

What this report does not do. It does not name a single preferred regimen, dose, or schedule. That requires the full current record, live guideline review, and the treating team's judgement.

Biomarker path · A MET-directed hypothesis

In Jane's case: the tissue result creates a biologically credible path, but confidence in the MET finding and access to an appropriate strategy must be established before relying on it.

Why it belongs in the conversation. Acquired MET amplification is a recognised bypass mechanism in EGFR-mutant lung cancer after EGFR-directed therapy. The liver biopsy was obtained at the time of systemic progression, making the timing clinically relevant.

What would have to be true before this became a therapeutic hypothesis

Key uncertainty. A tissue-plasma difference does not automatically invalidate either result. Tumour shedding, sampling location, assay sensitivity, and heterogeneity can all contribute.

Investigational · Clinical-trial evaluation

In Jane's case: a live trial screen may reveal options that combine EGFR-directed treatment, MET-directed treatment, antibody-drug conjugates, or other strategies, but the matches are preliminary.

Why it belongs in the conversation. The current profile has several elements commonly used for cohort assignment: metastatic non-squamous NSCLC, EGFR exon 19 deletion, prior osimertinib, tissue MET amplification, and ECOG 1.

What must be verified for every trial

• Recruitment status, active site, cohort availability, and geographic feasibility.
• Prior-line limits, measurable-disease rules, washout windows, and organ-function criteria.
• Whether the MET finding is required, allowed, or exclusionary for the specific cohort.

Practical trade-off. Trials may offer biological fit but introduce uncertainty, extra visits, travel, screening procedures, and the possibility of ineligibility after review.

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The next plan should be judged not only by tumour biology, but also by how it fits Jane's current health and priorities.

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We screened the registries against Jane's records and assessed the candidates criterion by criterion. This section keeps only the studies that could matter to her next decisions, ordered by how likely each is to help: treatment studies first, ranked by fit to the tumour and the phase of evidence, then by distance from home. Every study is a potential match that requires protocol and site confirmation; none is a statement of eligibility or a referral decision. Completed, non-recruiting and structurally mismatched studies are omitted; the wider screen is in the appendix for the treating team.

Two facts drive most of the open questions: the complete tissue MET report, and a current staging scan read against the trial's measurable-disease rules.

1. Treatment studies to screen for now

NCT07535437 · Ivonescimab with Dato-DXd or osimertinib (fictional) Treatment study · Phase 2 · Recruiting · Memorial Sloan Kettering, New York, 12 miles · Registry record Why it is here: the diagnosis, EGFR history, prior osimertinib and current performance status create a plausible match, and it is the closest treatment study to home. Open questions before referral:

• Confirm the exact cohort and its prior-treatment requirements with the study team.
• Whether a tissue MET amplification is required, allowed, or exclusionary for that cohort.
• Organ-function thresholds against the July liver enzymes.

2. Treatment studies relevant only if convincing progression is confirmed

(None in this fictional sample.)

3. Biologically interesting, not a match today

• NCT03778229 · SAVANNAH: osimertinib with savolitinib (fictional). Directly addresses the EGFR and MET resistance context and frames the biology, but the registry lists it as active and not recruiting. It becomes relevant only if a successor cohort opens.

4. Supportive and diagnostic studies

(None in this fictional sample.)

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1. Can we review the full MET result, including copy number, assay method, and the laboratory's threshold for amplification?
2. Would you recommend pathology or molecular-tumour-board review to reconcile the tissue and blood results?
3. What is the strongest standard-care benchmark at this point, and what benefit and toxicity should we expect?
4. If the MET finding is confirmed, which biomarker-directed approaches are realistically available to me?
5. Which trial should be verified first, and could your team contact the site before I travel?
6. How will each path affect my energy, independence, appointment burden, and time at home?

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Pathology. Initial biopsy: lung adenocarcinoma; TTF-1 and Napsin A positive, p40 negative. PD-L1 tumour proportion score 5%. Progression biopsy (May 2026): liver adenocarcinoma compatible with lung primary; no small-cell transformation.

Molecular and genomic profile

May 2026 plasma ctDNA: EGFR and TP53 detected; MET low-level or indeterminate; no other clearly actionable finding.

Plasma ctDNA report (18 May 2026): "MET copy number gain: low level, at the limit of detection; interpret with tissue results"

Radiographic course. March 2022 baseline thoracic primary with liver and bone metastases. July 2022 partial response. February 2024 limited iliac progression. October 2025 solitary liver progression. April to July 2026 multiple liver lesions and increased bone disease, then further hepatic progression with relatively stable thoracic disease.

Treatment history. Osimertinib from May 2022 to the present; durable initial control, then limited and later systemic progression. Iliac SBRT March 2024. Liver radiation November 2025.

Germline and familial considerations. No pathogenic germline finding in the supplied records. Germline testing should follow standard clinical indications rather than this report.

Limitations and information gaps

• The complete original molecular assay files and pathology slides were not independently reviewed.
• Trial status, cohort availability, site activity, and eligibility require live verification.
• This review has not been examined by a clinician. It draws on the records supplied, the applicable NCCN guideline, registry records, and cited literature.

Source inventory. Total Health personalized comprehensive review, drafted from the member's parsed records and the derived Total Health artifacts (patient journey, molecular profile, medications and labs, guideline mapping, alternatives analysis, clinical-trial screen), each with its generation date recorded in the member's record.

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1. Clarify the MET result. Gather the full tissue report and discuss assay details, pathology review, and whether orthogonal confirmation would change a decision.
2. Place the case in the current guideline pathway. Ask the treating oncologist to define the standard-care benchmark after systemic progression on osimertinib.
3. Compare the three paths explicitly. Review expected benefit, uncertainty, toxicity, visit burden, and quality-of-life impact for standard, biomarker-directed, and investigational approaches.
4. Verify the most credible trial first. Confirm recruitment, cohort, site, key eligibility rules, and travel practicality before any referral.
5. Bring the review to the treating team. Use the six questions above to decide what additional information is needed and who will own each follow-up.

Important disclaimer: this review draws on medical records, guidelines and clinical literature, but it does not provide medical advice or treatment recommendations. Always consult qualified healthcare professionals for medical decisions.

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