Treatments Beyond Surgery: Early-stage Options from ASCO 2022

Authors: Andrew Ciupek, PhD, Associate Director, Clinical Research and Daniel A. Saez, MSc, Manager, LungMATCH Navigation Program

People who are diagnosed with early stage (stage 1-2) non-small cell lung cancer (NSCLC) are generally broken down into two groups: those who can receive surgery to remove their tumor(s) and those who cannot. For both groups, it is important to consider how other treatments like radiation, chemotherapy and immunotherapy play a role in their treatment plan. At ASCO 2022, we learned about the latest treatments or people diagnosed with early stage NSCLC.

Treatment Options for Patients Whose Tumor Can be Removed

Lung cancer is considered most curable when the tumor can be removed surgically, however, surgery by itself does not provide the best odds for survivorship. Patients benefit from receiving treatments before (neoadjuvant) or after their surgery to help ensure that the tumor does recur.

• Data from the NADIM II clinical trial showed that adding Opdivo (nivolumab) to chemotherapy before surgery improves response rate and pathological response for patients with stage 3A and 3B NSCLC, further confirming its approval earlier this year. This is significant because it is the first time patients can receive immunotherapy with chemotherapy before their surgery to help improve the likelihood of surgery which cures the cancer.
• Data from the neoSCORE clinical trial was presented to determine the optimal number of cycles of neoadjuvant treatment for patients with stage 1B through 3A NSCLC. The conclusions of the trial are not definitive, but it was able to demonstrate that patients receiving three cycles of neoadjuvant immunotherapy and chemotherapy had a non-significant, but measurable, increase in response rate than those who received two cycles of treatment. Importantly, the extra cycle of treatment did not increase toxicity for patients on the trial.
• A study looking at cancer databases to determine whether or not adding radiation to chemotherapy before surgery improved outcomes for patients was also presented. Results from this study showed no increased response rate or pathologic response when adding radiation and concluded that chemotherapy alone might be a better option for patients eligible for surgery.

Treatment Options for Patients Whose Tumor Cannot be Removed

Some early-stage NSCLC cancer tumors cannot be removed surgically due to their size, location in the body and other factors. A combination of chemotherapy and radiation is most often used to treat these tumors and reduce the chance of recurrence. In addition, for certain stage 3B lung cancers that cannot be removed by surgery, the immunotherapy Imfinzi (durvalumab) can be given after chemotherapy and radiation to further reduce the chance of the disease returning. Despite these treatments, the cancer will often come back (especially when the stage at diagnosis is higher) underscoring the need for additional treatment options.

There were several research studies at ASCO 2022 that looked at new ways to treat inoperable early-stage NSCLC, most of which were focused on increasing the effectiveness of immunotherapy.

• Two-year follow up data from the Keynote 799 trial showed that using radiation treatment at the same time as chemotherapy and immunotherapy for inoperable stage 3 NSCLC, instead of the current standard treatment of using them sequentially, showed promising response and overall survival rates. Researchers believe that radiation to a tumor may make it more likely to respond to immunotherapy in certain cases. Research continues to identify which patients may respond best to this method.
• Data from the SPRINT trial indicated that for certain inoperable stage 2 and 3 lung cancers with high levels of PD-L1, treatment involving only immunotherapy and radiation produced positive results. With further research, researchers may be able to identify certain situations where these patients do not need chemotherapy as part of their treatment. The NRG-LU004 trial also showed that using the immunotherapy Imfinzi together with radiation (without chemotherapy) to inoperable NSCLC with high PD-L1 levels, was safe and that future research would help identify patients who may benefit from this approach.
• Data from a study looking at giving two different immunotherapy drugs, Opdivo (nivolumab) and Yervoy (ipilimumab), together after completion of chemotherapy and radiation for inoperable stage 3 non-small cell lung cancer found that the combination has similar results to giving Opdivo (nivolumab) alone, and caused additional side effects. This shows that Opdivo (nivolumab) and Yervoy (ipilimumab) together may not be an improvement over standard treatment.