Oncologists treating advanced non-small cell lung cancer (NSCLC) are increasingly adopting a two-year treatment duration as a standard approach for immunotherapy, balancing clinical efficacy with patient quality of life and financial considerations. This strategy is supported by evidence from original immunotherapy trials that discontinued treatment at the two-year mark, showing many patients maintained responses without disease relapse.
Evidence-Based Treatment Duration
Jonathan Thompson, MD, MS, a hematology and medical oncology specialist at Froedtert and the Medical College of Wisconsin, explained that "many of the original immunotherapy trials in [NSCLC] had very discontinued immunotherapy at the 2-year mark. What we see from the readouts of those trials is that many patients who had an ongoing response at 2 years—even after discontinuing the immunotherapy—were able to maintain response without disease relapse."
This approach represents a shift from indefinite treatment to a more targeted duration, with Thompson noting he commonly shoots for two years of therapy before considering discontinuation based on these trial data.
Biomarker-Guided Decision Making
Clinicians are incorporating circulating tumor DNA (ctDNA) testing to assess minimal residual disease (MRD) when making treatment discontinuation decisions. Thompson emphasized using these tools "to really try to understand if there is evidence of residual disease" and noted that "those who have a complete response with no clear evidence of residual disease generally have better long-term outcomes than those who still have evidence of disease at the 2-year mark."
The decision-making process involves comprehensive patient counseling about potential outcomes. "These are all conversations to have with the patient as we counsel patients early that we're shooting for at least 2 years of treatment for most," Thompson explained.
Addressing Financial Toxicity
Financial burden has emerged as a significant but understudied factor in treatment decisions. Lauren Antrim, MD, a medical oncologist at City of Hope Cancer Center Duarte, highlighted that "financial toxicity is very important, and it's not really studied as often as the other toxicities, and not reported in the adverse events usually on these big studies."
Patients who discontinue immunotherapy can be "alleviated from" financial toxicities by "no longer needing these expensive infusions [or] needing as many clinic visits," according to Thompson. Antrim emphasized that patients "deserve to be given the best care, and they shouldn't be penalized for it" while noting the importance of "investigating ways to allow patients to get the therapies that they need without breaking the bank."
Managing Treatment Risks and Benefits
The two-year timepoint also helps mitigate late-onset immune-related adverse events. Thompson noted that "even after 2 years, patients can incur new immune-related adverse events, so those risks can be mitigated by discontinuing treatment."
However, clinicians acknowledge the complexity of treatment discontinuation decisions. Some patients experience disease relapse after stopping immunotherapy, though Thompson noted that sometimes "the disease still remains sensitive to [immunotherapy], and we may reinitiate immunotherapy with success, but other times we see the disease is no longer sensitive to the immunotherapy."
Shared Decision-Making Approach
The treatment duration decision involves collaborative discussions between physicians and patients. Thompson emphasized that "it's truly a shared decision-making experience where I don't ever force patients off of immunotherapy if they're reluctant to do so, but a number of patients do see the value in discontinuing."
Future Research Directions
Ongoing research aims to further refine treatment duration strategies. Antrim referenced upcoming adaptive trial results that will "help investigate if shorter is better or longer is better in certain patients," questioning whether some patients could potentially stop after one year while others might need extended treatment.
The evolving approach to immunotherapy duration in advanced NSCLC reflects the field's maturation, moving beyond simple efficacy metrics to incorporate patient-centered outcomes including financial impact and quality of life considerations.
