Prescribed Minimum Benefit Status: Advanced Solid-Organ Malignancy

Abstract

Background. The Regulations to the Medical Schemes Act 131 of 1998 define when a solid-organ malignancy is “treatable” and therefore a prescribed minimum benefit (PMB). Where the anatomical limbs of that definition are not satisfied, a fourth limb applies: a well-demonstrated five-year survival rate of greater than 10% for the given therapy for the condition concerned. The operational consequences of this therapy-specific evidentiary test are difficult for benefit design, particularly when newer therapies have immature follow-up and medicine pricing is tightly regulated.

Methods. Overall survival (OS) landmark rates were assembled through a custom evidence program developed by the author. The program queries ClinicalTrials.gov (NCT) and PubMed APIs and structures study-level survival endpoints, which are then linked to condition, treatment context, biomarker and source study. Regimens are mapped to Froome Close concepts and the proprietary Froome Close oncology regimen pricing database for modelled per-course cost. The analysis uses advanced/non-curative solid-organ disease as a pragmatic proxy for settings in which the anatomical limbs are least likely to be satisfied; treatment intent itself is not part of the statutory definition. This is a regimen-library audit, not a systematic literature review.

Results. In the Froome Close research dataset snapshot, 86 advanced/non-curative solid-organ regimen records across 34 disease states met the analytical criteria. Twenty-five (29%) had a captured survival estimate at five years or beyond; 23 cleared the >10% threshold and two had a five-year estimate at or below 10%. Sixty-one records (71%) did not contain evidence sufficient to establish the five-year threshold from the captured data. This 71% figure is therefore a finding about evidence maturity and library completeness, not a literature-wide estimate. Fourteen high-cost records exceeded R500,000 per modelled course. Among usable within-state cost comparisons, dispersion remained material but was far smaller than the several-thousand-fold spread implied by incomplete ADT backbone costing.

Conclusions. Limb (iv) creates a structural tension rather than a simple cost-control rule. A strict reading can penalise recency or database lag, while a permissive reading can assume long-term benefit before it is demonstrated. At the same time, South Africa's single exit price (SEP) and section 18A framework materially constrains routine confidential, scheme-specific manufacturer concessions and risk-sharing, although regulated permanent and non-permanent SEP reductions do exist. The most defensible current response is live evidence verification, clinically appropriate formulary design and use of the remaining non-price levers. From a policy perspective, the reform choice need not be limited to retaining or abolishing SEP: an expressly authorised alternative-reimbursement pathway could address high-cost uncertainty while preserving transparent list pricing.

1. Introduction

Prescribed minimum benefits are the set of conditions and treatments that registered medical schemes must fund in full, irrespective of benefit option, under section 29(1)(o) of the Medical Schemes Act 131 of 1998 and its Regulations.¹ For oncology, entitlement turns on whether a malignancy is “treatable” as defined in the Regulations.

The definition distinguishes cancers of non‑solid organs and systems — the leukaemias, lymphomas and multiple myeloma — which qualify as PMB conditions irrespective of treatability, from cancers of solid organs, which qualify only if treatable. Solid‑organ malignant tumours are regarded as treatable where:

(i) they involve only the organ of origin and have not spread to adjacent organs;

(ii) there is no evidence of distant metastatic spread;

(iii) they have not, by compression, infarction or other means, brought about irreversible and irreparable damage to the organ of origin or another vital organ;

(iv) or, if points (i) to (iii) do not apply, there is a well demonstrated five‑year survival rate of greater than 10% for the given therapy for the condition concerned.²

Regulations to the Medical Schemes Act 131 of 1998. The Council for Medical Schemes (CMS) reproduces the same four-part test in its cancer guidance^3,4, including the requirement for a well-demonstrated five-year survival rate greater than 10% for the given therapy where the first three limbs do not apply. The exact provision and any current PMB definition guidance should be checked before a case-level determination.

Two features of limb (iv) are analytically decisive. First, the wording is therapy-specific: the survival rate is attached to “the given therapy”, not simply to the disease state. Second, the test is evidentiary: it asks for a well-demonstrated five-year survival rate. The difficulty is that a database may lack a five-year value because the trial is immature, because the evidence record has not been refreshed, or because the relevant long-term publication uses a different trial population or regimen grouping. This paper therefore distinguishes absence of captured evidence from evidence of absence.

2. Scope and case definition

Limb (iv) operates only where limbs (i) to (iii) are not satisfied. Those limbs are anatomical and functional; treatment intent is not itself part of the statutory definition. For this analysis, advanced, metastatic, relapsed and other non-curative disease states are used as a pragmatic proxy for settings in which the anatomical limbs are least likely to apply. That proxy cannot replace a case-specific assessment of stage, extent of spread and irreversible organ damage.

The analytical population is therefore restricted to advanced/non-curative solid-organ disease states in which treatability is most likely to be contestable. Cancers of non-solid organs and systems are excluded from this analysis because the solid-organ “treatable” definition is not the relevant gateway for those categories.

3. Methods

Overall survival landmark rates were assembled using a custom software pipeline developed by the authour. The program queries the ClinicalTrials.gov (NCT) and PubMed APIs, structures the retrieved study and publication data, and links survival landmarks to condition, treatment context, biomarker, source study and regimen concept identifiers. These records are joined to Froome Close regimen mappings and the proprietary Froome Close oncology regimen pricing database to generate modelled per-course costs. Cost modelling uses a body-surface-area basis of 1.79 m² where applicable and is reported in ZAR. The evidence dataset is a purpose-built research library rather than a systematic search of all subsequent publications, so current primary literature should be checked before operational use.

Because a survival function is monotonically non-increasing, a later-horizon rate above 10% guarantees that the five-year rate was also above 10%. The converse is not true: a later-horizon rate at or below 10% does not prove that the five-year rate was at or below 10%. Likewise, a sub-five-year estimate cannot by itself constitute a well-demonstrated five-year rate. The classification rule was therefore tightened as follows:

• Meets limb (iv) in captured evidence — a five-year estimate above 10%, or a later-horizon estimate above 10% that necessarily implies the five-year rate was above 10%.
• Fails limb (iv) on captured evidence — a five-year estimate at or below 10%. A later-horizon value at or below 10% is not, by itself, classified as failure at year five.
• Not established from captured evidence — no five-year estimate and no later-horizon value above 10% that can logically establish the threshold.

Classification was performed at regimen level to mirror the therapy-specific wording. Placebo, observation and best supportive care arms are retained in the appendix for context but are not treated as active formulary options in cost comparisons. “Not established from captured evidence” must not be interpreted as proof that no five-year publication exists outside the Froome Close dataset.

4. Results

4.1 Availability of five-year evidence

Eighty-six advanced/non-curative solid-organ regimen records across 34 disease states met the analytical criteria. In the Froome Close dataset snapshot, only 25 (29%) contained evidence sufficient to classify the five-year threshold, while 61 (71%) did not. This is a library-level evidence-maturity and data-currency finding; a live PMB decision requires a current search of the relevant primary literature.

Table 1. Classification of advanced/non-curative solid-organ regimen records against limb (iv), using the evidence captured in the Froome Close dataset.

4.2 Regimens failing the survival test

Two records with an explicit five-year estimate fell below the threshold: sorafenib monotherapy in first-line hepatocellular carcinoma (9.4% at five years; HIMALAYA)⁹ and carboplatin–nab-paclitaxel in first-line non-small cell lung cancer (6.8% at five years; POSEIDON)¹⁰. On a therapy-specific reading of the captured evidence, neither clears limb (iv), while other regimens in the same trial populations do: durvalumab–tremelimumab reaches 19.6% in HIMALAYA, and the addition of durvalumab to carboplatin–nab-paclitaxel reaches 13.0% at five years in POSEIDON.

This illustrates the therapy-specific character of the wording. Within a single trial, adding an agent can move a regimen from below to above the threshold. The implication is uncomfortable for cost containment: where the more effective regimen is also more expensive, limb (iv) can support PMB eligibility for the costlier option rather than functioning as a cost-control device.

4.3 High-cost records without a five-year estimate captured in the library

At the database snapshot used for this analysis, fourteen records with modelled per-course costs above R500,000 did not contain a five-year estimate. The original library also lacked mature follow-up for several immunotherapy records. These observations should be read as a data-currency signal, not as proof that no later or parallel five-year publication exists.

Table 2. Regimen records costing more than R500,000 per course with no five-year estimate captured in the Froome Close dataset snapshot.

Best OS (overall survival) denotes the longest-horizon estimate captured for that record.

Evidence-currency note. “No five-year estimate captured” is a property of this Froome Close dataset snapshot. Current primary literature includes long-term follow-up not represented in several rows; examples include KEYNOTE-407,¹² KEYNOTE-006¹³ and CheckMate 214.¹⁴

4.4 Cost dispersion among qualifying regimens

Eight disease states contained at least one active-treatment record meeting limb (iv) in the captured evidence. Cost dispersion remained material, but the original several-thousand-fold estimate was driven by ADT combination rows in which the hormonal backbone had not been costed. After correcting the ADT–bicalutamide and ADT–flutamide entries to an approximate R24,000 benchmark, the widest clearly usable within-state spread shown in Table 3 is more than six-fold in first-line maintenance ovarian cancer (R271,443 to R1,745,041).

Table 3. Active-treatment records meeting limb (iv) in the captured evidence, with comparator arms retained only where explicitly labelled.

Estimates within a disease state frequently derive from different trials, populations and follow-up periods and are not directly comparable. Cost figures are model outputs rather than tariffs and should not be used for fine ranking where a treatment backbone is incomplete (see §5.2 and §7).

Costing correction. The original ENZAMET-linked ADT + bicalutamide and ADT + flutamide values (R17 and R37) omitted the ADT backbone. They are shown here at approximately R24,000 as a transparent proxy anchored to the bicalutamide + goserelin benchmark. Actual cost depends on the GnRH agent/depot, antiandrogen duration, pack selection and current SEP.

5. Mitigation strategies and their limitations

Where a condition qualifies as a PMB, payment obligations and the lawful use of formularies, protocols, designated service providers and co-payments must be assessed under the Medical Schemes Act and Regulations. Limb (iv) itself contains no explicit cost-effectiveness threshold. The practical funding problem therefore shifts from a binary survival test to the harder question of which therapy is clinically appropriate, how that choice can be expressed in an evidence-based formulary, and what pricing or contracting mechanisms remain available.

5.1 The pricing framework: what it constrains

Much of the international health-economics repertoire for high-cost oncology — confidential discounts, price-volume agreements, pay-for-performance rebates and managed entry agreements — assumes a lawful route for payer-specific manufacturer concessions. South Africa's SEP framework materially constrains that route in the private sector. The position should not, however, be reduced to “no price movement is possible”: the National Department of Health maintains formal processes for permanent and non-permanent SEP reductions.

Section 22G of the Medicines and Related Substances Act establishes the transparent pricing framework, while section 18A prohibits bonus, rebate and incentive systems.⁵ Together, these provisions create substantial obstacles to informal or confidential scheme-specific net-price concessions and many outcome-linked rebate structures. Whether any particular alternative reimbursement arrangement is lawful depends on its design and requires specialist legal and regulatory advice.

The practical consequences for benefit design are:

• No routine confidential scheme-specific manufacturer discount. A medical scheme cannot simply rely on the kind of undisclosed net price below a public list price that is common in some rebate-driven markets.
• Formal price reductions do exist, but through regulated SEP mechanisms. Permanent and non-permanent SEP reduction processes are available^6,7; they are regulatory price mechanisms rather than an ordinary bespoke confidential rebate negotiated for one scheme.
• Risk-sharing is difficult to operationalise. Outcome-linked rebates, free-goods arrangements, dose caps and related structures can engage section 18A and SEP concerns and do not have a simple, clearly established route within routine private-sector reimbursement.

The practical corollary is that direct medicine-price negotiation is constrained, so schemes lean heavily on evidence-based regimen and formulary selection together with other non-price levers: designated-provider and network arrangements, generic or biosimilar substitution where appropriate, dose and wastage optimisation, site-of-care choices, and treatment-duration or stopping rules. The economic question is therefore not simply “what is the cheapest qualifying regimen?”, but “what is the least costly option that is clinically appropriate for this beneficiary and defensible on current evidence?”

A methodological consequence is that the modelled costs in this analysis do not assume confidential payer-specific rebates. They should nevertheless not be treated as precise pathway costs: formal SEP changes, pack-size selection, treatment duration, omitted backbone drugs, administration, supportive care and wastage can all materially change the total.

5.2 Formulary design: the least costly clinically appropriate qualifying regimen

Regulation 8(4) preserves the scheme's ability to employ appropriate interventions aimed at improving the efficiency and effectiveness of health care provision, including formularies and protocols (regulations 15H and 15I). Regulation 8(5) then permits a co‑payment where a formulary drug is clinically appropriate and effective for the beneficiary's PMB condition and the beneficiary knowingly declines it in favour of another. Regulation 15G requires that any limitation of coverage be developed on the basis of evidence‑based medicine, taking cost‑effectiveness and affordability into account, and be disclosed on request. This is the lawful vehicle for preferring one qualifying regimen over another, and it is a scheme‑side instrument requiring no agreement with the manufacturer.

Why the crude version is fragile:

• The statutory and regulatory framework makes clinical appropriateness central. A formulary preference is difficult to defend if the preferred option is not clinically appropriate and effective for the individual beneficiary. A crude “cheapest qualifying regimen” rule therefore risks turning a cost-ranking exercise into a clinical exception problem.
• Cross-trial heterogeneity materially confounds a naive ranking. In castrate-sensitive prostate cancer, the corrected proxy cost for ADT–bicalutamide is approximately R24,000 because the original database entry omitted the ADT backbone; its 57% five-year value derives from the ENZAMET setting. The R105,301 enzalutamide–leuprolide record with 78.9% at eight years derives from EMBARK in biochemically recurrent disease, a substantially different and generally better-prognosis population. The apparent survival difference is therefore strongly confounded by case mix, making a cross-trial price floor difficult to defend clinically.
• The cheapest qualifying regimen may be clinically obsolete. Dacarbazine monotherapy has a five-year survival estimate above the threshold in first-line melanoma, yet modern checkpoint inhibition has changed standard care. A regimen can satisfy a numerical survival threshold and still fail the practical test of contemporary clinical appropriateness.
• Within-trial comparisons can sometimes favour escalation on both clinical and cost axes. In CameL¹¹, adding camrelizumab to carboplatin–pemetrexed improved five-year OS in the captured trial data while the modelled per-course cost was lower than for the comparator. Where a valid like-for-like comparison exists, a blanket price floor can forgo both benefit and savings.
• Biomarker‑defined subgroups break the average. Qualifying status computed across a disease state may be inapplicable to a molecularly defined subgroup in which only a targeted agent is active. In first‑line maintenance ovarian cancer, all qualifying estimates are HRD‑positive; extrapolation beyond that subgroup is unsupported.
• Displaced cost is not saved cost. Restricting to less effective regimens shifts expenditure into progression, subsequent lines and admission. Medicine spend may fall while total cost of care rises. The evaluation must be pathway‑level, not pharmacy‑level.

Properly constructed, a formulary remains a defensible instrument: it can prefer the least costly option that is clinically appropriate, evidence-based and supported by a valid comparison, while maintaining a documented exception pathway. What is fragile is a crude floor derived from incomplete costs, cross-trial ranking or obsolete comparators.

5.3 Strict application of the evidentiary requirement

Limb (iv) asks for a well-demonstrated five-year survival rate. A literal approach can treat a record without captured five-year evidence as unable to establish the limb. In this Froome Close dataset snapshot, 71% of records fell into that category. That figure should not be converted into a blanket denial rule because it can reflect both genuine trial immaturity and evidence-library lag.

Why it is fragile:

• It can penalise recency or data capture rather than inefficacy. A missing five-year value may reflect the age of the trial, the publication selected for the database or a failure to ingest later follow-up. The relevant question for a live determination is whether current evidence establishes the threshold, not whether one dataset record contains it.
• It may also sit uneasily with a purposive reading of the PMB framework. The apparent policy purpose is to distinguish advanced cancers with meaningful treatability from futile treatment, not to make entitlement turn on the update cycle of a database. Any denial based solely on an absent library field would therefore be particularly vulnerable to challenge.
• It produces an unstable benefit if evidence maturity alone controls entitlement. A patient's position could change when a long-term follow-up paper is published even though the clinical state is unchanged.
• It can cut against the scheme. Applied consistently, the therapy-specific test can exclude an older comparator while a more expensive intensified regimen clears the threshold, as the POSEIDON example illustrates.

5.4 Alternative reimbursement models: constrained by the current framework

Where a high-cost agent has uncertain mature survival, comparator systems may use coverage with evidence development, outcome-linked contracts or price-volume arrangements. These instruments address the uncertainty directly rather than trying to resolve it through a binary PMB eligibility dispute.

In South Africa, there is no straightforward routine pathway for confidential payer-specific arrangements of this kind under the current SEP and section 18A framework. Formal permanent and non-permanent SEP reductions exist, but they are regulated price mechanisms. More complex outcome-linked or risk-sharing structures require careful legal and regulatory design and may need an expressly authorised pathway. The policy problem is therefore a structural gap, not proof that every conceivable alternative model is automatically unlawful.

Clearly available levers are narrower but not limited to regimen selection: formal SEP reduction processes, dose and administration optimisation, treatment-duration and stopping rules, generic or biosimilar substitution where genuine equivalence exists, site-of-care management and designated service provider arrangements. A targeted reform option would be to supplement SEP with an expressly authorised alternative-reimbursement channel with clear governance, auditability, confidentiality rules and patient-access safeguards; full repeal of SEP is not the only conceivable route.

6. Discussion

Four findings bear on benefit design. First, in the Froome Close dataset snapshot the numerical threshold itself was rarely the limiting factor once mature evidence was captured: 23 of 25 classified records cleared 10%. This supports the view that limb (iv) is usually more consequential as an evidence and therapy-selection problem than as a simple “10%” hurdle. The exact proportions should not be treated as current literature estimates without a full evidence refresh.

Second, the binding constraint is evidentiary asymmetry and data currency. Seventy-one percent of records in the Froome Close dataset did not establish the five-year threshold from captured evidence. Some will be genuinely immature; others may simply lag later publications. Literalism can therefore exclude effective newer therapies or stale records, while permissiveness can assume long-term benefit before it is demonstrated.

Third, the therapy-specific wording cuts both ways. It can support differentiation between regimens within a disease state, but the two explicit five-year failures in the library also show that the regimen clearing the threshold may be the more expensive option. Limb (iv) is not inherently a cost-containment instrument.

Fourth, the pricing framework limits the direct price-negotiation lever that many comparator systems use. Formal SEP reduction mechanisms exist, but routine confidential payer-specific risk-sharing remains difficult. As a result, evidence-based formulary design and other provider, utilisation and pathway levers carry more weight than they do in rebate-driven systems.

The practical implication is that PMB eligibility and appropriate therapy should be adjudicated as distinct questions. A live case should first use current evidence to assess the statutory threshold; it should then use evidence-based clinical criteria to define appropriate care and any lawful formulary preference. Database absence should never be equated with evidence absence, and cost should not substitute for clinical appropriateness.

7. Limitations

• Cross‑trial heterogeneity. Estimates within a disease state derive from different trials, eras and populations. Comparisons across regimens are confounded by case mix and are presented as evidence of dispersion, not of relative effect.
• Approximation of “state of advancement”. Advanced/non-curative treatment context is used as a pragmatic proxy for settings in which limbs (i) to (iii) are unlikely to apply. It does not reproduce the statutory anatomical test and cannot replace patient-level staging, extent of spread or organ-damage assessment.
• Library composition and currency. The database is regimen-anchored and is not a systematic literature review. Disease states without effective therapy are under-represented, while some records use earlier or regional publications despite later global follow-up. “Not established from captured evidence” may therefore reflect update lag rather than true absence of five-year evidence.
• Cost model. Per-course costs are modelled and exclude some administration, supportive care, wastage and pathway costs. The original ADT–bicalutamide and ADT–flutamide entries (R17 and R37) omitted the ADT backbone and have been replaced with an approximate R24,000 proxy anchored to the bicalutamide–goserelin benchmark. This is a benchmarking correction, not a tariff. Other incomplete backbone costs should not be used for fine ranking without re-costing against the current SEP database.
• Legal interpretation. Classification applies the treatable-cancer wording reproduced in CMS guidance and secondary sources citing the Regulations. The current Regulations, Annexure A, relevant PMB definition guidance and any applicable rulings should be verified before a determination. CMS guidance itself notes that the legislated Regulations prevail where there is conflict with interpretive lists or guidance.
• Regulatory analysis is not legal advice. The characterisation of SEP, section 18A and the PMB formulary framework is offered as policy and benefit-design analysis, not a legal opinion. Any co-payment, formulary or manufacturer arrangement should be settled with appropriately qualified legal and regulatory advisers.

8. Conclusion

Applied as a regimen-library audit, the >10% five-year survival test is satisfied by almost every record with mature evidence captured, while many records cannot be classified from the data held. That pattern exposes a real problem, but not quite the one suggested by a literal database read: the test can be distorted by trial maturity and evidence-library lag, while cost ranking is distorted by cross-trial heterogeneity, clinical obsolescence and incomplete costing. Neither strict “no five-year field, no PMB” logic nor a “fund the cheapest qualifying regimen” rule is defensible as a general solution.

The deeper financing problem is that the current SEP and section 18A framework significantly constrains routine scheme-specific price concessions and risk-sharing, while formal SEP reductions do not replicate the flexibility of confidential payer-specific contracts. The practical response today is a combination of live evidence verification, clinically appropriate formulary design and the remaining non-price levers. For policy reform, the choice need not be framed as simply retaining or abolishing SEP: an expressly authorised alternative-reimbursement pathway could preserve transparent list pricing while allowing controlled outcome-based or conditional agreements. Until such a pathway exists, evidence uncertainty and affordability pressure remain difficult for funders to resolve without risking either inappropriate denial or unsustainable open-ended liability.

ABOUT THE AUTHOR Nicholas Downey is a medical doctor working in the managed care industry.

References and sources

The following sources were used for statutory context, current policy framing and targeted evidence. The quantitative analysis itself uses the independently developed Froome Close research dataset and proprietary oncology regimen pricing database described in §3. Legal provisions should be confirmed against the current Regulations and Government Gazette before use in a determination.

1.Medical Schemes Act 131 of 1998, s 29(1)(o); Regulations, GN R1262 of 20 October 1999, as amended — reg 8 (prescribed minimum benefits; payment in full; formulary co-payment at reg 8(5)); reg 15G (limitation on disease coverage); reg 15H (protocols); reg 15I (formularies); reg 15J (general provisions); Annexure A (diagnosis and treatment pairs).

2.Regulations to the Medical Schemes Act 131 of 1998, Annexure A, Explanatory Note 3 — definition of “treatable” solid-organ malignancy, limbs (i)–(iv), including the five-year survival rate of greater than 10% for the given therapy for the condition concerned.

3.Council for Medical Schemes. CMScript: When is cancer a PMB? Member newsletter, February 2009.

4.Council for Medical Schemes. CMScript 12 of 2021: Lung Cancer — reproduces the four-part “treatable” cancer definition, including limb (iv).

5.Medicines and Related Substances Act 101 of 1965, s 18A (prohibition of bonus systems, rebate systems and incentive schemes); s 22G (pricing committee; transparent pricing system; single exit price).

6.Regulations Relating to a Transparent Pricing System for Medicines and Scheduled Substances, made under s 22G of Act 101 of 1965, as amended — reg 6 (single exit price).

7.National Department of Health. Pharmaceutical Economic Evaluation portal and medicine-pricing resources, including the Database of Medicine Prices — 30 June 2026 and templates for permanent and non-permanent SEP reductions.

8.Council for Medical Schemes. Circular 14 of 2026: PMB Definition Guideline Development and Invitation for Expert Participation in the Clinical Advisory Committee.

9.Rimassa L, Chan SL, Sangro B, et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. J Hepatol. 2025. doi:10.1016/j.jhep.2025.03.033.

10.Peters S, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy in first-line metastatic NSCLC: five-year overall survival outcomes from the phase 3 POSEIDON trial. J Thorac Oncol. 2025;20(1):76-93.

11.Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed as first-line therapy for advanced non-squamous non-small-cell lung cancer: 5-year outcomes of the CameL randomized phase 3 study. J Immunother Cancer. 2024;12(11):e009240.

12.Novello S, Kowalski DM, Luft A, et al. Pembrolizumab plus chemotherapy in squamous non-small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study. J Clin Oncol. 2023;41(11):1999-2006.

13.Long GV, Carlino MS, McNeil C, et al. Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study. Ann Oncol. 2024;35(12):1191-1199.

14.Tannir NM, Albigès L, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2024;35(11):1026-1038.

Source trials. Survival estimates in the Froome Close dataset are identified per record in Appendix A by source study.

Survival evidence in this review derives from the author’s independently developed Froome Close research dataset, assembled through the ClinicalTrials.gov (NCT) and PubMed APIs.

Regimen costs derive from the proprietary Froome Close oncology regimen pricing database. This is a regimen-library audit, not a systematic literature review. Targeted QA identified later or global long-term follow-up not reflected in some dataset records, including KEYNOTE-407, KEYNOTE-006 and CheckMate 214; current primary literature should therefore be checked before any case-level PMB determination.

Appendix A. Supporting data

All 86 advanced/non-curative solid-organ regimen records in the Froome Close research dataset snapshot, by condition and treatment context. OS is the estimate at five years or beyond where captured (bold); otherwise the longest available shorter-horizon estimate is shown. Classification is per §3 and describes the evidence held in the Froome Close dataset, not the totality of published evidence.

Key: Meets (iv) in captured evidence Fails (iv) on captured five-year evidence Not established from captured evidence