Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma): lines of therapy

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5 standard-of-care settings across 4 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	Fit
Screening, prevention and diagnosis	1	·
Advanced, first line	·	1
Second line	1	·
Other settings	2	·

Screening, prevention and diagnosis

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Work-up	Exclude favourable subsets; comprehensive genomic profiling of tissue or plasma; assess performance status and lactate dehydrogenase.	Histopathology & immunohistochemistryComprehensive genomic profilingLiquid biopsy (ctDNA)Tumour-agnostic (tissue-agnostic) approval	ESMO Clinical Practice Guideline on cancer of unknown primary 2023	95

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
Fit	First line, fit patients	Platinum-based doublet (carboplatin-paclitaxel or gemcitabine-cisplatin) for three cycles, then continuation or a switch to molecularly guided therapy where an actionable alteration is found (CUPISCO).	CarboplatinPaclitaxel / nab-paclitaxelGemcitabine + cisplatinCUPISCOPlatinum agents	ESMO Clinical Practice Guideline on cancer of unknown primary 2023	91

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Second line	Alternative chemotherapy, PD-1 antibody if not given (nivolumab approved in Japan), or trial entry; trials of antibody-drug conjugates and immunotherapy combinations.	NivolumabPembrolizumabA Phase II/III Study of F520 Combined With Paclitaxel Plus Carboplatin in the Treatment of Cancer of Unknown Primary (CUP)	ESMO Clinical Practice Guideline on cancer of unknown primary 2023	98

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Actionable alterations	Tumour-agnostic therapies: pembrolizumab or nivolumab for MSI-high or high tumour mutational burden, NTRK inhibitors, BRAF and MEK inhibitors, HER2-directed therapy.	PembrolizumabNivolumabTumour-agnostic (tissue-agnostic) approvalComprehensive genomic profiling	ESMO Clinical Practice Guideline on cancer of unknown primary 2023	98
All comers	Poor performance status	Best supportive care with early palliative care involvement.	Pain relief and palliative care are unavailable to most	ESMO Clinical Practice Guideline on cancer of unknown primary 2023	0

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.