This is the third recap blog in our series of updates from the World Conference on Lung Cancer (WCLC), held in San Diego from September 7-10, and the European Society for Medical Oncology (ESMO) conference, held in Barcelona from September 13-17. This update focuses on early-stage and locally advanced non-small cell lung cancer (NSCLC).
You can read the other update blogs from these fall science meetings:
For this blog, we will refer to stage I and stage II NSCLC as early-stage NSCLC and stage IIIA and stage IIIB NSCLC as locally advanced NSCLC.
In the discussion of therapies below, keep in mind that neoadjuvant refers to treatment given before the main treatment, and adjuvant is treatment that follows the primary treatment.
Early-Stage NSCLC
Surgery continues to be the most important treatment option for eligible people. Currently, stage I NSCLC is treated with surgery. Immunotherapy is not given as part of neoadjuvant (before surgery) treatment; however, the cancer can come back in high-risk individuals. Recent research shows that neoadjuvant immunotherapy may stop the cancer from coming back in this group of people.
Immunotherapy's role in treating early-stage lung cancer continues to be reinforced. Updated results from the IMpower-010 trial show that adding immunotherapy after surgery as adjuvant treatment decreases the chances of cancer metastasis.
Immunotherapy combinations (such as nivolumab targeting PD-1 and ipilimumab targeting CTLA-4 on immune T cells) are also being tested as neoadjuvant treatment. These combinations do not have a chemotherapy component and seem to work better in cancers that do not have multiple mutations (mutations in the KRAS, STK11, KEAP1, and SMARCA4 genes).
Perioperative immunotherapy (given as neoadjuvant treatment before surgery and as adjuvant treatment after surgery) seems to be more effective than neoadjuvant treatment alone at keeping early-stage cancer from coming back after surgery.
Results from the Checkmate 77T and the AEGEAN trials suggest that ctDNA (circulating tumor DNA shed from cancer cells and found in the blood) is decreased more in people who received both neoadjuvant and adjuvant immunotherapy than in those who received only neoadjuvant immunotherapy. ctDNA in the blood may imply that the cancer has a higher risk of coming back after surgery. Comparing the Checkmate 816 trial (using only neoadjuvant immunotherapy) to the Checkmate 77T trial suggests an added benefit of adjuvant immunotherapy, but phase 3 trials are needed to confirm this finding.
We are indeed starting to push the boundaries of perioperative immunotherapy. Updated results from the NeoCOAST-2 trial suggest that combining new treatments with immunotherapy as neoadjuvant followed by adjuvant treatment improves cancer control after surgery. The NeoCOAST-2 trial specifically tested the following new treatments:
- Oeclumab, which blocks the CD73 protein
- Monalizumab, which blocks the NKG2A protein and increases activation of the immune system
- Dato-Dxd, an antibody-drug conjugate targeting the TROP2 protein
There is a role for targeted therapies in the treatment of early-stage NSCLC that has a targetable biomarker. Alectinib, a drug that blocks the effects of ALK fusions in NSCLC, is now approved as adjuvant treatment for early-stage NSCLC based on the results of the ALINA trial. Updated results from the trial show that the drug works in both the V1 and the V3 types of ALK fusions, the two most common types of ALK fusions found in NSCLC. In addition, tumors that had mutations in the TP53 gene showed worse outcomes with alectinib.
Stereotactic ablative radiotherapy (SABR) combined with immunotherapy may be a suitable treatment option for inoperable stages I and II NSCLC, based on the results of the I-SABR trial. Taking findings of the trial a bit further, the I-SABR research team added an artificial intelligence (AI) model to further personalize the treatment regimen. The AI model included the clinical characteristics of the person in treatment and the radiological characteristics (how the cancer looked on a CT scan) of the cancer. The researchers found that the AI model improved the prediction for which people would benefit from the I-SABR treatment approach.
As these new treatment options show, early-stage treatment is becoming more and more personalized.
Locally Advanced NSCLC
The recent LAURA trial reported that when given after chemoradiation, the EGFR mutation-blocking drug osimertinib improves outcomes in people diagnosed with stage IIIA or stage IIIB NSCLC with an EGFR mutation. New data from the LAURA trial suggest that osimertinib protects against metastasis outside the lung, including the brain—a common site of metastasis in this patient group.
Radiation pneumonitis is inflammation of the lungs caused by radiation treatment to the chest area. It is a common side effect seen after chemoradiation in stage III treatment. Adding osimertinib did not increase the chances of developing radiation pneumonitis. This is an important point to note given that side effects from treatment need to be discussed when making treatment decisions.
Surgically Operable Locally Advanced NSCLC
Several clinical trials (AFT-46: CHIO3 and NADIM 1) confirm that chemotherapy plus immunotherapy as neoadjuvant treatments improve outcomes of surgically operable stages IIIA and IIIB NSCLC. These trials also show that clearance of ctDNA seems to be a predictor of whether the cancer will come back after treatment.
It is important to note that depending on the size and location of the cancer, how much the cancer has spread, and the person’s health status, sometimes surgery may be offered to people with locally advanced NSCLC.
If you haven’t watched the discussion on early-stage NSCLC by Dr. Jarushka Naidoo at the International Lung Cancer Survivorship Conference, there is still time. You can register here and watch the video today. Stay tuned for our final (fourth) blog post, which will focus on screening and early detection of lung cancer.