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Dosing immunotherapy combinations: Analysis of 3,526 patients for toxicity and response patterns

Mina Nikanjam1, Harsh Patel2, Razelle Kurzrock3

  • 1Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA.

Oncoimmunology
|September 19, 2017
PubMed

Insights

Combining immunotherapies for metastatic cancer shows promise. Anti-PD-1/PD-L1 agents can be safely combined with other treatments, often at reduced doses, with three-drug regimens improving response rates.

Area of Science:

  • Oncology
  • Immunotherapy
  • Clinical Trials

Background:

  • Metastatic cancer treatment increasingly utilizes immunotherapy combinations.
  • Evidence for safe starting doses of novel immunotherapy combinations is limited.
  • Understanding dose optimization is crucial for improving patient outcomes.

Purpose of the Study:

  • To analyze the safety and dosing of combination immunotherapy regimens in adult clinical trials.
  • To determine dose reductions required for various immunotherapy combinations.
  • To evaluate the impact of combination therapy on response rates.

Main Methods:

  • Review of Phase I-III adult clinical trials involving immunotherapy combinations (anti-PD-1, PD-L1, CTLA-4).
  • Data collected from PubMed and major oncology conference abstracts (2010-2016).
  • Calculation of dose percentages relative to single-agent recommended doses.

Main Results:

  • 84 studies with 3,526 patients and 59 combinations were analyzed.
  • Anti-PD-1/PD-L1 agents could be administered at full dose in 63% of studies.
  • Three-drug combinations demonstrated significantly higher response rates than two-drug combinations.

Conclusions:

  • Anti-PD-1/PD-L1 checkpoint inhibitors are safely combinable with targeted agents and other immunotherapies, often at reduced doses.
  • Combinations with cytotoxic agents were generally tolerable at full doses.
  • Three-drug regimens offer superior response rates compared to two-drug regimens in metastatic cancer.
Keywords:
Immunotherapymaximum tolerated doseprecision medicinerecommended phase 2 dosetargeted therapy

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