The benefits delivered by combining treatments compared with sequencing those treatments was a recurrent theme at the annual ESMO 2017 Congress (#ESMO17). This issue is driven by the exceptionally rapid clinical developments in oncology, which have been demonstrated by the recent approvals of immune checkpoint inhibitors across different indications.

Some key unanswered questions that were raised at ESMO on the topic of sequencing included:

 

How can we know if the combination provides better efficacy than the sequence? And how is toxicity impacted by combination versus sequential treatments?

On Friday, during the Educational Session “Immunotherapy: The next steps”, there were interesting presentations regarding the combination of agents targeting the immune system and how to best sequence immunotherapy to gain maximum efficacy in malignant melanoma. It was illustrated that sequential treatment sequences might provide better survival outcomes that combining therapies. With major advances in adjuvant treatment options, particularly in melanoma as highlighted at the third Presidential Symposium, it was also noted that the adoption of adjuvant therapies will impact sequences of treatment for those that relapse with metastatic disease.

On Sunday, during the Poster Discussion Session “Genitourinary tumours, non-prostate” professionals expressed divided opinions regarding the sequencing of immunotherapies in bladder cancer due to the little available strong data to guide choice of therapy. Some physicians need a longer follow-up to evaluate post-progression outcomes before they feel comfortable to re-treat a patient with PD-1 inhibitor after previous PD-1/PD-L1 therapy. However, others feel the lack of data available regarding therapy choice post-progression is not a strong argument to withhold additional PD-1 agents, especially in indications where there are very limited options available for patients who progress after immunotherapy inhibition (e.g., bladder cancer).

 

How should we sequence immunotherapy successfully to extend patients survival? Should new drugs be used after or before progression? Lack of data to answer these questions compound treatment choice uncertainty.

As mentioned during the Special Symposium “Access to innovative drugs in the EU” on Monday, there is a need for a greater number of trials to address the outcome of sequencing treatments. There are multiple combination trials and multiple sequencing trials ongoing, including trials that start with one therapy and then switch to another at the time of progression; however, trials which evaluate combination treatments versus the sequencing of the same therapies have not been seen yet, and will require extensive collaborative efforts.

 

Do we really need clinical trials to reveal the most successful combination or sequencing of immunotherapies? Efficacy is usually the primary driver of treatment choice! Immune checkpoint inhibitors have impressive results; however, their use may have some restrictions which can reduce their commercial opportunity (e.g., such as patient eligibility and development of immune related adverse events). Recruiting sufficient patients into clinical trials is also an obstacle to generating clinical data.  Analysing real world evidence from the current clinical practice of patients treated with these therapies provides real time insights into current clinical practice and with expert insight, we can determine the main drivers influencing prescribing choice.

 

Our new Treatment Sequencing solution helps you identify physicians most frequent treatment sequences in commercially important populations and treatment scenarios. Our new monthly updated Real World Brand Tracker service uses real world claims data to help you quickly understand the competitive environment among ICIs across oncology indications. For more insights on oncology drug development, follow @LauraVinuesaDRG

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