By Jill Daigneault, PhD
Surgical outcomes for early-stage NSCLC are still very poor due to the high rate of recurrence through distant metastases. It is likely that these distant metastases are present at initial resection as undetectable micrometastases. In order to target these potential sites of recurrence in early-stage patients, trials using immunotherapy (IO) and tyrosine kinase inhibitors (TKI) approved for recurrent and late-stage lung cancers are being conducted in pre- and postoperative settings.
Phase II studies of adjuvant IO in patients with early-stage NSCLC have shown great promise and many have moved into phase III trials. The results of these trials are eagerly awaited. The CTONG1104: ADJUVANT trial showed that disease-free survival (DFS) for patients with EGFR-mutant (EGFRm) NSCLC was significantly improved. However, these results did not translate to a significant improvement in overall survival (OS). Further studies into adjuvant treatment with targeted therapies still need to be conducted.
“There seems to be a wave of precision medicine in perioperative care,” Dr. Tsuboi told Virtual Presidential Symposium News. “Adjuvant therapy aimed at controlling micrometastases seems to be shifting from the postoperative setting alone to perioperative treatment (ie, pre- and post-operative treatment.) It is important to deliver perioperative treatment to those who can be expected to respond to the treatment based on blood samples, biopsy specimens, or resected specimens. A risk–benefit balance should be considered when determining a treatment plan for each patient, considering that some patients may be cured by surgery alone.”
Trials in the neoadjuvant space have shown strong results even in early phases. Neoadjuvant IO in early-stage NSCLC has shown reduction in tumor size as measured by major pathological response in phase II trials. However, these pathologic results did not always align with the radiologic response and objective response rate. Five major phase III trials investigating neoadjuvant IO treatment are ongoing.
Although the results from the phase III IO trials have yet to be released, the use of TKIs in the adjuvant setting has shown practice-changing potential. The results from the ADAURA trial presented at the 2020 ASCO Annual Meeting Virtual Scientific Program show a significant increase in DFS in patients with early-stage EGFRm NSCLC. This is the first targeted therapy to show such improvements in this patient population. It has yet to be reported if these results translate to OS.
“In my opinion preoperative immune checkpoint inhibition is a promising strategy, and I am convinced that it will become standard of care in the future,” Dr. Tsuboi said in an interview. “Although it is undisputed that risk–benefit considerations should determine the indication for treatment, early diagnosis and early therapeutic intervention for immune-related adverse events should be kept in mind when approaching treatment and adverse events associated with perioperative treatment should be avoided as much as possible.”