Cetuximab fails India’s cost-effectiveness test unless biosimilar price halves

India’s flagship publicly financed health insurance scheme may be paying far too much for one of the few targeted therapies proven to extend survival in head and neck cancer. A team of health economists and oncologists from the Post Graduate Institute of Medical Education and Research (PGIMER) in Chandigarh, together with colleagues at Government Medical College and Hospital, has built a detailed economic model showing that cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR), does not deliver good value for money at its current price in India. The analysis, published in Frontiers in Pharmacology, examined two clinical scenarios: adding cetuximab to radiotherapy for locally advanced head and neck cancer patients who cannot receive cisplatin-based chemoradiotherapy, and adding the drug to platinum-based chemotherapy for patients with recurrent or metastatic disease. In neither case did the treatment clear India’s official cost-effectiveness threshold, although a halving of the biosimilar cetuximab price would change the verdict for locally advanced disease.

The stakes are enormous. Head and neck cancers rank as the seventh most common malignancy worldwide but the third most common cancer in India, where 1.56 million new cases and 874,404 deaths were reported in 2024. Nearly 90% of these tumours are squamous cell carcinomas that overexpress EGFR, a molecular feature linked to aggressive behaviour, poorer outcomes and resistance to radiotherapy. More than 65% of Indian patients present with locally advanced disease, and roughly 30% to 35% of them are ineligible for cisplatin-based chemotherapy, the current standard of care. For this substantial cisplatin-ineligible group, international guidelines recommend adding cetuximab to radiotherapy rather than radiotherapy alone. The pivotal evidence comes from the phase III Bonner trial, which showed median locoregional control of 24.4 versus 14.9 months, progression-free survival of 17.1 versus 12.4 months, and overall survival of 49.0 versus 29.3 months when cetuximab was combined with radiotherapy compared with radiotherapy by itself.

Despite this proven clinical benefit, access to cetuximab in India remains poor because of its high cost. In a retrospective audit from Tata Memorial Hospital in Mumbai, of 2,796 platinum-refractory head and neck squamous cell carcinoma patients eligible for immunotherapy, only 41 patients, or 1.47%, actually received it, with financial unaffordability cited as the dominant barrier. One route to expanding access would be inclusion of the drug in the health benefits package of Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB PM-JAY), India’s government-funded insurance programme. As part of that decision-making, India’s national health technology assessment agency sought India-specific evidence, because previous economic evaluations from Europe, the Netherlands and Taiwan found radiotherapy plus cetuximab cost-effective, while analyses from China, Canada and the United Kingdom found cetuximab plus chemotherapy not cost-effective for recurrent or metastatic disease. Heterogeneous populations, cost structures and willingness-to-pay thresholds limit the generalizability of that evidence, and the recent introduction of a biosimilar cetuximab added a further reason for a fresh Indian analysis.

The PGIMER team constructed a Markov model in Microsoft Excel to simulate the lifetime costs and health outcomes of treatment. For the locally advanced analysis, the model comprised five mutually exclusive health states: progression-free survival, locoregional recurrence, distant metastasis, all-cause mortality and disease-specific mortality. For the recurrent or metastatic analysis, four states were used: progression-free survival, progressive disease, all-cause mortality and disease-specific mortality. Both models started patients at 56 years of age, the median age of diagnosis for head and neck cancer in India, and cycled monthly, matching the published Kaplan-Meier curves and standard treatment protocols. Future costs and health consequences were discounted at 3% annually, and an abridged societal perspective was adopted in line with Indian health technology assessment guidelines, excluding indirect costs from productivity losses. Treatment sequences were modelled in detail: radiotherapy delivered as 70 Gy in 35 fractions over 7 weeks, with cetuximab given as a 400 mg/m2 loading dose one week before radiotherapy followed by 250 mg/m2 weekly, and chemotherapy consisting of cisplatin 100 mg/m2 plus fluorouracil 1,000 mg/m2 for 4 days every 3 weeks for up to 6 cycles, with maintenance cetuximab until progression in the intervention arm.

Clinical effectiveness data were drawn from the phase III randomised trials. The Bonner trial supplied transition probabilities for the locally advanced analysis and the EXTREME trial for the recurrent or metastatic analysis, the latter having shown that adding cetuximab to platinum-based chemotherapy increased progression-free survival by 2.3 months and overall survival by 2.7 months. Published Kaplan-Meier curves were digitised and reconstructed into approximate patient-level data, and parametric survival models using exponential, Weibull, log-logistic, log-normal, generalized gamma and Gompertz distributions were fitted, with the final distribution selected on statistical fit, visual comparison and clinical plausibility. Disease-specific mortality rates were derived from Indian 5-year survival estimates weighted across oropharyngeal, hypopharyngeal and laryngeal cancer sites, yielding an overall 5-year survival of approximately 30.4%, and all-cause mortality came from Indian Sample Registration System lifetables. Health-state utility weights were obtained from the nationally representative CaDCQoL study, which interviewed 1,113 head and neck cancer patients across six Indian states using the EQ-5D-5L tool, giving a progression-free utility of 0.603 and a recurrence or metastasis utility of 0.458.

Costs were estimated from an abridged societal perspective, incorporating direct non-medical expenditure such as travelling, boarding, food and informal payments alongside health system costs. Radiotherapy and chemotherapy regimens were priced using reimbursement rates under the PM-JAY scheme, which bundle drugs, investigations, day-care charges, supportive care and professional fees; intensity-modulated radiotherapy was costed at ₹70,000, three-dimensional conformal radiotherapy at ₹21,000 and two-dimensional conformal radiotherapy at ₹11,000. Because cetuximab and certain immunotherapy agents are not covered by any publicly financed scheme, market prices were used: ₹11,000 per 100 mg vial for original cetuximab and ₹6,500 for the biosimilar. Dosage calculations assumed a body surface area of 1.6 m2, based on weighted average Indian anthropometric data, so the 640 mg loading dose required seven 100 mg vials, with the residual 60 mg counted as wastage because vial sharing was not assumed. The model also included costs of managing commonly occurring grade 3-4 adverse events, and grade 2-4 skin toxicity for cetuximab, with all inputs standardised to 2024-25 rupees.

The results are stark. Adding biosimilar cetuximab to radiotherapy for cisplatin-ineligible locally advanced patients yielded 2.73 quality-adjusted life years (QALYs) compared with 2.45 QALYs for radiotherapy alone, an incremental gain of 0.28 QALYs, but at an additional lifetime cost of ₹138,548 per patient, producing an incremental cost-effectiveness ratio (ICER) of ₹501,320 per QALY gained. With original cetuximab, the ICER rose to ₹871,632 per QALY. India’s published cost-effectiveness threshold is one-time per capita gross domestic product, equivalent to ₹247,045, or about US$2,697, for 2024-25, meaning the locally advanced combination costs 2.02 times the threshold per QALY gained. The recurrent or metastatic scenario fared far worse: adding biosimilar cetuximab to chemotherapy produced only 0.04 incremental QALYs at an extra ₹610,776 per patient, an ICER of ₹15,023,037 per QALY, or 60.8 times the per capita GDP, with the original molecule pushing the ratio to ₹24,693,072 per QALY. At the current price, neither strategy is cost-effective under India’s recommended willingness-to-pay threshold.

The model’s most consequential finding concerns price. A 50% reduction in the biosimilar cetuximab price would bring the median ICER for radiotherapy plus cetuximab down to ₹222,239 per QALY, below the national threshold, with a 64.9% probability of being cost-effective in probabilistic sensitivity analysis; a 60% price cut would raise that probability to 87.3%. Probabilistic sensitivity analysis, run over 999 Monte Carlo simulations with gamma distributions on costs and beta distributions on utilities and probabilities, confirmed the direction of the findings, and alternative survival distributions shifted the locally advanced ICER by only modest amounts, from an 8.1% decrease with the Gompertz distribution to a 9.2% increase with the Weibull distribution, without changing any conclusion. For the recurrent or metastatic analysis, alternative distributions increased the ICER by 22% to 35.8%, again leaving the intervention not cost-effective. The authors validated the model against published literature, showing locoregional control rates and a 27.2% reduction in locoregional recurrence risk with cetuximab consistent with the Bonner trial’s reported 32% risk reduction, and a modelled 5-year survival of 50.9% with radiotherapy alone consistent with Indian estimates.

The study carries important limitations that the authors acknowledge openly. Transition probabilities were derived from international trial evidence because robust India-specific estimates do not exist, and the Bonner trial included a mixed population rather than being conducted exclusively in cisplatin-ineligible patients, since no phase III trial has directly compared radiotherapy plus cetuximab with radiotherapy alone in that specific group. Pembrolizumab-based immunotherapy, now a preferred first-line option for recurrent or metastatic disease in international guidelines, was excluded because the policy question framed by the National Health Authority concerned cetuximab specifically; grade 1-2 adverse events and indirect productivity costs were also omitted, the latter consistent with Indian reference-case guidance. Even so, the policy implication is clear: the analysis does not support including cetuximab at current market prices in India’s health benefits package, but strategic purchasing through price negotiation could make biosimilar cetuximab a worthwhile addition for cisplatin-ineligible locally advanced patients under AB PM-JAY. For recurrent or metastatic disease, the gap between current price and the threshold is so wide that cost-effectiveness is unlikely at any plausible near-term discount, though the authors call for further research in clinically relevant subgroups, such as patients with a combined positive score below 1 and those with oral cavity tumours, to identify the populations most likely to benefit from this targeted therapy.

Subject of Research: Cost-effectiveness of cetuximab for head and neck cancer treatment in India

Article Title: Cost-effectiveness analysis of cetuximab for the treatment of head and neck cancers in India

Article References: Gupta, N., Dixit, J., Jyani, G., & Prinja, S. (2026). Cost-effectiveness analysis of cetuximab for the treatment of head and neck cancers in India. Frontiers in Pharmacology, 17, Article 1948615. https://doi.org/10.3389/fphar.2026.1948615

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1948615

Keywords: cetuximab, cost-effectiveness analysis, head and neck cancer, biosimilars, quality-adjusted life years, health technology assessment, India, Ayushman Bharat PM-JAY, Cost-effectiveness, analysis, treatment, head