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Dean A, Byrne A, Marinova M, Hayden I. Clinical outcomes of patients with rare and heavily pretreated solid tumours treated according to the results of tumour molecular profiling. Biomed Res Int. 2016;2016:4627214.

Patients with rare and heavily pretreated solid tumours show significant clinical benefit after Caris Molecular Intelligence-guided treatment

It is well documented that patients who have rare tumours or heavily pretreated advanced cancers present unique challenges with regards to treatment. In these patients, recognising who is likely to respond to treatments is complicated by increasing tumour heterogeneity (i.e. multiple molecular changes) as tumours metastasise. Research shows that molecular profiling with Caris Molecular Intelligence (CMI) can feasibly be used in clinical practice for patients with difficult-to-treat tumours to improve patient outcomes.1

This Australian-based study included 54 patients who were divided into 3 groups: those with heavily pretreated tumours (n=31), those with rare tumours (n=16), and those who had received prior standard therapy (n=7). All patients underwent CMI molecular profiling and were subsequently treated in-line with the results of the report generated through profiling. A best unprofiled treatment choice, which was physician determined, was documented before profiling. This enabled the treatment identified through profiling to be compared to what the physician would have chosen without profiling. The treatment recommendations identified by CMI profiling were different to physician recommendations in 88.9% of cases (n=48). The researchers noted that this indicates the difficulty in selecting treatments for patients with advanced tumours and that CMI could be a “valuable aid to clinical decision-making” for these patients.

Importantly, the researchers found that 60% of the patients attained significant clinical benefit after treatment in-line with the CMI report. Clinical benefit was based on investigator-assessed response or PFS ratio (ratio between PFS on CMI-guided therapy vs the PFS on the most recent prior line of therapy) ≥ 1.3. Investigator-assessed response included changes in pain, body weight, performance status, patient-reported quality of life, tumour marker levels and symptom relief.

The majority of the treatments that were recommended by CMI profiling were common chemotherapy agents. This finding is echoed in other research in which CMI has been used to inform treatment decisions. 2 The researchers noted that this propensity to recommend chemotherapy agents is a “significant potential advantage” and that CMI provides “rational, evidence-based treatment selections often based on standard chemotherapy regimens with no apparent bias toward novel targeted/biological therapy.” The researchers also noted that although 16 patients were recommended targeted/biological therapies, in most of the cases the recommended therapy was not available or funded and it was only able to be used in 4 cases. For the cases where it was not able to be used an alternative CMI-guided chemotherapy treatment was used. This approach is something which would not be possible with services that offer Next Generation Sequencing-only as they are more likely to recommended targeted therapies only.2

Summary

  • Recently published research has demonstrated the clinical benefit CMI profiling for patients with rare or heavily pretreated advanced tumours.
  • 60% of patients in the study experienced significant clinical benefit when they were treated in-line with the treatment recommendations identified by CMI profiling.
  • Treatment recommendations identified by CMI profiling differed from physician recommendations in 88.9% of cases emphasising the complexity of such tumours and the majority of recommendations were widely available chemotherapy agents.

References

  1. Dean A, Byrne A, Marinova M, Hayden I. Clinical outcomes of patients with rare and heavily pretreated solid tumours treated according to the results of tumour molecular profiling. Biomed Res Int. 2016;2016:4627214. [Full text]
  2. Russell KJ, Janssens J, Dean A, Hernandez A, Voss A. Treatment choices based on multiplatform profiling platform, unlike those with sequencing alone, do not cause a cost explosion in refractory cancer patients. Value in Health. 2017;20(9):A579. [PDF]
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