Peek behind the paper: real-world evidence for evaluating a novel melanoma treatment
In this feature, we take a peek behind the paper with contributing authors Matthew Perez and Jonathan Zager: the COSMUS-I study.
The COSMUS-I study was undertaken on the back of significant advances over the last decade in the treatment of melanomas with targeted and immuno-therapies. COSMUS-I aimed to assess the efficacy of talimogene laherparepvec (T-VEC) – a novel melanoma therapy – as a routine clinical practice treatment for metastatic melanoma patients in the USA.
In this feature, we peek behind the paper with contributing study authors Matthew Perez and Jonathan Zager – both from the Moffitt Cancer Center (FL, USA) – to discuss the contribution and importance of real-world evidence (RWE) to the COSMUS I study.
What prompted you to conduct this research?
Currently, there are multiple treatment options available for patients with advanced, locoregional melanomas. In this study, we wanted to specifically assess the real-world use and adoption of a novel approach to melanoma management; this new therapy – known as T-VEC, or ImlygicTM – comprises an oncolytic virus carrying the gene for GM-CSF.
“The RWE and data we obtained concerning the efficacy of T-VEC in our patient cohort was highly consistent with what has previously been observed in controlled clinical trials.”
How did RWE complement data obtained from previous clinical trials concerning T-VEC?
The RWE and data we obtained concerning the efficacy of T-VEC in our patient cohort was highly consistent with what has previously been observed in controlled clinical trials. In fact, the RWE suggested that T-VEC may even be more efficacious compared with what has been previously observed. This is likely due to the potential for some patients, in our real-world study, to receive concurrent systemic immunotherapy (off protocol) treatment for their melanomas. This combination therapy was not allowed for clinical trial participants. Additionally, the data from this study was consistent with previous clinical trial data with respect to recorded adverse events; T-VEC treatment was tolerated well and the majority of adverse events were mild in nature.
What was the rationale behind the screening criteria you employed to define your study cohort and what limitations did these impose?
In this study, we were interested in gathering data concerning the use and efficacy of T-VEC as an intralesional treatment for metastatic melanoma, specifically for patients outside of a clinical trial setting. This meant that all participants were not receiving the standard of care approved treatment for their melanoma, before study commencement. Any patients who had participated in a clinical trial or expanded access program for T-VEC were excluded from study inclusion.
These criteria aimed to ensure that we were assessing the true benefits of first-time exposure to T-VEC, in patients for whom other standard therapies had failed.
“…we were assessing the true benefits of first-time exposure to T-VEC, in patients for whom other standard therapies had failed.”
The only limitation imposed by these criteria was that the patient cohort receiving T-VEC treatment was restricted.
Some patients did not complete the full course of T-VEC treatment due to physician recommendation or at their own request; were these reasons investigated and what may the implications of these be on the outcomes of your study?
There are a few reasons for this; some patients who were withdrawn from T-VEC treatment were done so because they did not tolerate T-VEC very well. However, this was very rare in the study; T-VEC was overwhelmingly well tolerated in patients. Further, some patients might not have required continued T-VEC treatment; they may have experienced a complete response and no longer presented with lesions to inject. Other patients might have failed T-VEC treatment and were therefore changed to a different metastatic melanoma treatment.
These reasons for patient withdrawal from T-VEC treatment have no implications on the outcomes of the study; our study conclusions are valid based on the data, taking into account all reasons for discontinuation.
What may the implications of the study be on the use of RWE in decision making and clinical trial design?
There are limited implications of this study on future clinical trial design. However, due to our employment of RWE and our assessment of patients outside of a controlled clinical trial setting, this retrospective study may allow readers to understand the prospects of their patients who are to be treated with T-VEC in the future. This could allow clinicians to prognosticate and counsel their patients as to what to expect from the treatment, such as responses and side effects.
“…due to our employment of RWE…this retrospective study may allow readers to understand the prospects of their patients who are to be treated with T-VEC in the future.”
Are you aware of any other RWE-based studies in the field of melanoma treatment research?
There are many retrospective reviews and outcomes research investigations that describe treatment algorithms and results in the field of melanoma treatment.
Of particular interest, there is another multi institutional study, currently underway, assessing the outcomes resulting from T-VEC use in combination with immunotherapy.
Do you have future RWE studies planned for T-VEC?
We are currently planning a follow up study to this COSMUS-I study; this ‘COSMUS II’ study hopes to describe greater uses of T-VEC in a number of more diverse patient populations. For example, the ‘COSMUS II’ trial will incorporate the results of patients who are receiving concurrent therapies for their melanoma treatment whilst receiving T-VEC (off protocol).
Our ‘COSMOS II’ study will hopefully be submitted by the end of this year.
Financial and competing interests disclosures:
Matthew Perez: Research funding for this project from Amgen (CA, USA)
Jonathan Zager: Research funding for this project from Amgen. Consultant fees from Amgen. Speakers bureau Amgen.