Immunotherapy Treatment Updates from ASCO 2022: Combinations, Resistance and More

Author: Daniel A. Saez, MSc, Manager, LungMATCH Navigation Program

Many patients with non-small cell lung cancer (NSCLC) rely on a class of treatments called immunotherapy to battle their cancer. The significant difference between immunotherapy and targeted therapy (the other main type of treatment that patients with NSCLC receive) is that no biomarker is used that can directly predict whether the immunotherapy will work.

Because of this unpredictability, there is ongoing research to better understand which patients respond well to immunotherapy and if there is any way to predict their response—like combining immunotherapy with other types of treatment. Another key area of immunotherapy research is focused on what to do for patients who receive immunotherapy and then progress after a period of time.

How Oncologists Increase Efficacy of Immunotherapy: Combinations and Other Considerations

Many patients who receive immunotherapy as a treatment also receive chemotherapy to help increase the immunotherapy’s efficacy.  However, researchers have been studying other combinations that could provide the same benefit without chemotherapy or potentially provide better results.

• Immunotherapy and immune modulating treatments
  One approach researchers are taking is to identify if combining immunotherapy with other immune modulating treatments, such as anti TIGIT drugs, will increase survival for patients. This research is ongoing and the populations of patients with NSCLC who might benefit the most from these combinations is still being identified. However, to date, clinical trials have not shown a positive increase in survival or increase in time to progression for patients who receive this combination in the first-line setting.
• New types of immunotherapy treatments
  Studies highlighting new types of immunotherapy treatments such as vaccines, adoptive cell therapies and antibody treatments were also presented at ASCO. Much of the data for these novel types of treatments are still being explored and many of the studies are very small. Because of this, conclusions on how well these novel treatments might work are difficult to make. However, the research on new types and combinations of immunotherapies is only getting started and the future for this field is promising.

Resistance is Not Futile: How Oncologists Approach Continued Treatment with Immunotherapy

One of the most difficult situations people with lung cancer face is deciding their next treatment (second line) after their first line of treatment stops working. This can be especially difficult for patients who do not have actionable biomarkers. Second-line treatment for patients with no actionable biomarkers would normally be chemotherapy and immunotherapy combinations that are very similar to the regimens that the patient may have already progressed on.

• Adding VEGFR inhibitors
  One potential option for patients who have progressed on immunotherapy is to add a type of drug that affects the ability of the tumor to get blood, a VEGFR inhibitor. Two ASCO presentations demonstrated that VEGFR inhibitors could be a beneficial addition for patients and might provide better outcomes than immunotherapy, alone. While this combination is not yet approved by the FDA, promising research in this space is ongoing and will hopefully provide a new option for people with lung cancer in the future.
• Finding new immune markers to target
  A second option for patients who have progressed on standard PD-1/PD-L1 based immunotherapy (the most common in the US) is the combination of chemotherapy with immunotherapies that target a different immune marker other than PD-1/PD-L1. Similar work has been done in the past with an immune marker called CTLA-4 but did not show better outcomes for patients. However, promising research might lead to the discovery of new options to target.

In addition to outlining potential strategies for patients who have progressed on immunotherapy, ASCO 2022 also featured the latest on efforts to determine what genetic markers might help predict resistance and response to immunotherapy. While there has been some consistency on a few genes, like STK11, which have a direct correlation with resistance and progression there is still more work to be done, particularly as it relates to the tumor microenvironment (TME). TME refers to the cells, blood vessels, and other molecules that surround the tumor and how they behave. Researchers are coming closer and closer to determining how TME composition could relate to the genetics of the tumor and how to best use that information for immunotherapy treatment.