At the recently concluded 2023 European Lung Cancer Congress (ELCC), Professor Luis Paz-Ares from Madrid University Hospital in Spain presented results from a Phase II trial called CARMEN-LC05 (NCT04524689). The results showed that the antibody-drug conjugate (ADC) targeting CEACAM5, Tusamitamab ravtansineA, in combination with or without pembrolizumab, and chemotherapy, produced responses in CEACAM5-positive non-squamous non-small cell lung cancer (NSCLC) patients in the first-line treatment, and it was well-tolerated. In an interview with Oncology Frontier, Dr. Luis Paz-Ares shared his insights on the key highlights of the 2023 ELCC conference and addressed some clinically relevant questions.
Can you share your impressions of the 2023 ELCC conference? What topics at this conference caught your attention the most?
I believe that the 2023 ELCC conference was a highly educational event. This conference provided updates and insights into the latest developments in various aspects of lung cancer diagnosis and treatment compared to standard protocols. Importantly, it presented data updates from various studies and new results from Phase III trials.
One significant highlight of this conference was the new data from the CheckMate-816 trial, which demonstrated more mature data on the benefits of neoadjuvant chemotherapy combined with nivolumab in early-stage non-small cell lung cancer. Furthermore, the CheckMate-816 study suggested that inflammatory features may predict the benefits of this combination therapy. Updated data from the APPLE trial indicated that osimertinib remained a better treatment option than sequencing third-generation TKIs even when disease progression was monitored using liquid biopsies (monitoring EGFR resistance mutations in ctDNA) in first-line therapy. The conference also reported the results of two negative trials: the second part of the Phase III RESILIENT trial showed that experimental liposomal irinotecan monotherapy did not provide any advantages in overall survival (OS) and progression-free survival (PFS) compared to topotecan in patients with small cell lung cancer (SCLC) who had progressed during or after first-line platinum-based chemotherapy. The CONTACT-01 trial showed that atezolizumab + cabozantinib did not improve the prognosis of metastatic NSCLC patients who had previously failed immunotherapy and chemotherapy.
You presented a poster at the 2023 ELCC on the ongoing BO42777 platform study (131TiP), which evaluates various therapies in locally advanced unresectable Stage III NSCLC patients. Could you tell us about this study?
This is a typical platform study for unresectable Stage III non-small cell lung cancer patients. The idea behind designing this study is that if you perform genomic analysis on unresectable Stage III NSCLC patients, many of them will have identified driver gene mutations, some of which can be targeted with specific TKIs. The BO42777 trial aims to identify driver gene mutations (such as ALK, ROS, RET, etc.) in unresectable Stage III NSCLC patients who have previously received ≥2 cycles of concurrent or sequential chemoradiotherapy (the standard treatment for unresectable Stage III NSCLC) and then provide them with targeted inhibitor therapy (alectinib for ALK+, entrectinib for ROS1+, or pralsetinib for RET fusion+) while the control group receives standard therapy with durvalumab. Although post-concurrent chemoradiotherapy treatment with durvalumab is the standard treatment for unresectable Stage III NSCLC patients, patients with driver gene mutations still need better treatment options.
The use of chemotherapy in PD-L1 high-expressing patients is a highly debated topic. When treating advanced NSCLC with high PD-L1 expression using immune checkpoint inhibitors, do you recommend combination with chemotherapy?
Currently, for PD-L1 high-expressing advanced NSCLC without driver gene mutations, two strategies are available: monotherapy with immune checkpoint inhibitors or combination therapy with chemotherapy and PD-1/PD-L1 inhibitors, both suitable for NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥50%. The question is which patients should receive monotherapy with tumor immunotherapy (IO) and which should receive chemotherapy + IO.
In principle, we tend to lean toward using monotherapy with immunotherapy for most PD-L1 high-expressing patients because it is simpler and less toxic compared to chemotherapy + IO. However, for patients at risk of early progression or those who require a very rapid treatment response (possibly due to severe symptoms or highly aggressive tumor biology), we lean toward using chemotherapy + IO. Other factors, such as PD-L1 expression being around 50% or lower or having a low tumor mutation burden, may also make patients more likely to benefit from chemotherapy + IO compared to those with PD-L1 expression close to 100% or a high tumor mutation burden. Of course, we also consider patient preferences and opinions.
Based on current clinical trial results, are there any differences in the efficacy of PD-1 inhibitors and PD-L1 inhibitors for extensive-stage small cell lung cancer (ES-SCLC)?
Currently, some trial data suggest that both PD-1 inhibitors and PD-L1 inhibitors are effective in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Personally, I believe that there may not be a significant difference between these drugs. However, in Western countries, two immune therapy drugs (atezolizumab and durvalumab) have been approved for treating ES-SCLC, and both of these drugs are PD-L1 inhibitors. Trials using PD-1 inhibitors (such as pembrolizumab) for the treatment of ES-SCLC yielded negative results at the technical level because the difference in benefits between the two groups did not reach statistical significance, even though the results appeared similar to several other positive trials. Therefore, we tend to follow the drug labels, which currently require the use of durvalumab or atezolizumab when using immunotherapy to treat ES-SCLC. It should be noted that a trial conducted in the Chinese ES-SCLC population showed positive results for PD-1 inhibitor therapy.
