Reply to 'Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers'.

We welcome the position paper by the European Society for Medical Oncology on issues surrounding biosimilars.1 After recent approval of the first biosimilars of monoclonal antibodies (mAbs) in oncology, the input of medical oncology societies to an open discussion of medical opinion and provision of guidance regarding the introduction of these drugs into clinical practice are urgently needed.

As pointed out by Tabernero et al, safety and efficacy of biosimilars are the shared responsibility of manufacturers and regulatory bodies. We agree that a robust regulatory framework for authorisation of biosimilars is in place in Europe, and properly developed and approved biosimilars can be considered a valid treatment option.2

In line with the authors and the whole pharmaceutical industry,3 we advocate that the decision whether a reference product or biosimilar is dispensed to a patient has to be retained by the prescribing physician and based on clinical judgement. Patients should be engaged in these decisions and must know which biologic they receive. Transparency across all levels and prescription by brand name are critical factors to ensure adequate pharmacovigilance.

What is currently missing from a regulatory perspective are formal, evidence-based standards and guidelines to ensure patient safety in the context of switching between a reference product and its biosimilar(s). National healthcare systems may encourage such a switch to reduce costs.

mAbs are a highly complex class of biologics, and mAb biosimilars have only just started to become available in oncology. Tabernero et al urge physicians to be well informed about the products prior to making a decision on switching. At present, the consequences of switching a patient with cancer stable on an mAb reference product to a biosimilar are unknown. There is no clinically relevant evidence available yet from any studies investigating such a switch in an oncology indication (table 1).

Table 1

Overview of switching studies with biosimilar monoclonal antibodies in advanced development or already approved for cancer treatment

Reference product (name, manufacturer)	Biosimilar (name, manufacturer)	Study	Indication	Design	Availability of switching data
Rituximab (MabThera, Roche; Rituxan, Genentech/Biogen Idec)	CT-P10 (Truxima, Celltrion)	CT-P10 1.3 NCT01873443	Rheumatoid arthritis	Open-label extension of phase I study, with a one-sided single switch (MabThera→CT-P10 (non-randomised), n=20).	Publication5
		CT-P10 3.2 NCT02149121	Rheumatoid arthritis	Open-label extension of phase I/III study, with a one-sided single switch (MabThera→ CT-P10 (non-randomised); Rituxan→CT-P10 (randomised)).	Not yet published
		CT-P10 3.4 NCT02260804	Low tumour burden follicular lymphoma	Phase III study with a one-sided single switch (Rituxan→CT-P10 (non-randomised) during maintenance treatment phase).	Not yet published
	GP2013 (Rixathon, Sandoz)	ASSIST-RT GP13-302 NCT02514772	Rheumatoid arthritis	Phase III study in patients previously treated with MabThera or Rituxan, with a one-sided single switch (Rituxan/MabThera→GP2013 (randomised)).	Not yet published
	PF-05280586 (Pfizer)	REFLECTIONS B328-04 NCT01643928	Rheumatoid arthritis	Extension of phase I/II study with a one-sided single switch (MabThera→PF-05280586 (randomised), n=65; Rituxan→ PF-05280586 (randomised), n=60).	Limited data on ClinicalTrials. gov
	BCD-020 (Biocad)	BCD-020–02 NCT01759030	Rheumatoid arthritis	Phase III study with a two-sided single switch (ie, from each treatment to the other: BCD-020→MabThera (randomised); MabThera→BCD-020 (randomised) after 24 weeks of treatment).	Not yet published
Trastuzumab (Herceptin, Roche)	ABP 980 (Amgen)	ABP 980 NCT01901146	Early breast cancer	Phase III study with a one-sided single switch during the adjuvant phase (following surgery; Herceptin→ABP 980 (randomised)).	Not yet published

Current evidence on the impact of switching between reference product mAbs and their biosimilar(s) is limited mainly to studies in inflammatory diseases.4 Importantly, results of switching studies with individual products cannot be generalised to other biologics and their biosimilars.

As more biosimilars become available, more complex switching scenarios might be possible, such as switching between biosimilars (these products have not been directly compared with each other in clinical studies) and switching back and forth between products. Such switching scenarios are associated with an even higher level of residual uncertainty.

Conclusions

Patients deserve the best available treatment for better outcomes and potential cure. The introduction of biosimilars can improve oncology patients’ access to potentially life-saving biologics. However, safety considerations and the potential for cure should remain first priority and not be outweighed by potential cost reduction aspects.

We support physicians’ ability to prescribe based on their assessment of the totality of data available, their personal experience and in consultation with the patient.

To enable proper decision-making and ensure that a switch does not negatively impact safety and efficacy of treatment, relevant clinical evidence is needed, including appropriate data from switching studies with biosimilars in the oncology setting and guidance from medical societies.