Worldwide, lung cancer caused an estimated 1.8 million deaths in 2020 [33]. In the United States, there are over 230,000 new cases of lung cancer and 130,000 deaths annually [34]. In recent years, immunotherapy (with or without chemotherapy) and targeted agents against specific mutations (EGFR, ALK, K-RAS, and others) have dramatically improved the survival of these patients. The U.S. FDA recently approved neoadjuvant nivolumab plus chemotherapy for patients with resectable NSCLC. However, patients with resectable disease (stage IIIA) still lack a standard treatment approach.
The results of the NADIM II study were presented by Mariano Provencio-Pulla, MD, PhD (Hospital Universitario Puerta de Hierro, Madrid, Spain) [35]. The study enrolled 86 patients who were randomly assigned to receive nivolumab plus carboplatin-based chemotherapy or chemotherapy alone. The primary endpoint was pathological complete response (pCR). The trial found that neoadjuvant nivolumab plus carboplatin-based chemotherapy improves pCR for patients with resectable stage IIIA NSCLC compared with chemotherapy alone: 36.8% versus 6.9%, correspondingly. The addition of nivolumab to chemotherapy did not significantly increase toxicity. This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. It means that we can expect a change in the standard of care for these patients.
KRAS mutations account for 25% of oncogene-driven NSCLC cases, and understanding the clinical features of these tumors may be critical for optimized treatment algorithms.
Oladimeji Akinboro (Center for Drug Evaluation and Research, U.S. FDA, Silver Spring, MD USA) presented “Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: U.S.FDA pooled analysis.” [36] This study looked at outcomes of first-line ICIs, with or without chemotherapy, based on the KRAS mutation status and PD-L1 expression.
The authors pulled data from 12 registrational clinical trials investigating first-line checkpoint inhibitor-containing regimens and found no significant difference between KRAS wild-type and mutant for overall survival regardless of the regimen used. This analysis suggests that patients with KRAS-mutated NSCLC benefit from 1L chemo-ICI similarly to those with KRAS wild-type NSCLC and should receive combination therapy upfront. Patients with KRAS-mutated NSCLC derived the most significant benefit from the combination of chemo-ICI compared to ICI or chemo alone. Clinical trials investigating targeted therapies for KRAS-mutated NSCLC in the 1L should include a chemo-ICI comparator arm.
The combination of TKI and chemotherapy has shown improved clinical outcomes in advanced EGFR mutated NSCLC patients. Brain metastases are a critical issue for patients with EGFR-positive NSCLC, considering a baseline incidence of about 25-30%, with uncertain treatment perspectives due to the low intracranial activity of most medications used for NSCLC treatment.
Likun Chen (Department of Medical Oncology, Sun Yat-sen University Cancer Center, China) presented findings from an open-label, randomized, multicenter, Phase 3 study in which patients with EGFR-mutated non–small cell lung cancer and brain metastases were randomized to receive gefitinib alone or gefitinib plus pemetrexed-platinum chemotherapy until intracranial progressive diseases, unacceptable adverse, or any cause of death [37]. The study showed an increased median intracranial PFS of 15.6 months in the gefitinib plus chemotherapy group versus 9.1 months in the gefitinib group (P < 0.001). Similarly, the median PFS was significantly longer with gefitinib plus chemotherapy than with gefitinib alone (16.3 months versus 9.5 months, P < 0.001). Median OS was 35.0 months in the gefitinib plus chemotherapy group versus 28.9 months in the gefitinib group. Based on the findings from the study, the authors concluded that in untreated EGFR-mutated NSCLC patients with brain metastases, gefitinib plus chemotherapy was superior with respect to improved intracranial PFS, PFS, and a tendency of OS than gefitinib alone, and could be the optional first-line treatment.