Dr Chiang on Managing Advanced NSCLC Without Driver Mutations

Anne Chiang, MD, PhD, associate professor, Medicine, Section of Medical Oncology, associate cancer center director, Clinical Initiatives, Yale School of Medicine, Yale Smilow Cancer Hospital Care Center, discusses treating patients with advanced non–small cell lung cancer (NSCLC) without driver mutations.

In stage 4 lung cancer without a driver mutation, investigators are witnessing a convergence of PD-L1 staining, various co-mutations, and histology, which collectively aid oncologists in devising a more personalized treatment approach for patients with NSCLC, Chiang begins. Notably, the NSCLC treatment armamentarium has seen a remarkable expansion in recent years, she explains. Chiang says that in 2020, she reviewed the treatment options for this patient population, noting that these options were limited to pembrolizumab (Keytruda) alone or in combination with chemotherapy. However, the current treatment options include several additional regimens, such as nivolumab (Opdivo) with ipilimumab (Yervoy) plus or minus 2 cycles of chemotherapy; durvalumab (Imfinzi) and tremelimumab (Imjudo) plus 4 cycles of chemotherapy; and cemiplimab-rwlc (Libtayo).

The variety of NSCLC treatment choices provides a diversified approach to addressing the complexities of individual patient cases, Chiang expands. Furthermore, the accumulation of 5-year data from trials such as the phase 3 KEYNOTE-189 trial (NCT02578680) is particularly encouraging, she notes. In KEYNOTE-189, the 5-year OS rate with pembrolizumab plus pemetrexed and platinum in patients with nonsquamous NSCLC was 19.4%, a substantial improvement compared with historical outcomes, even though aspirations for further progress persist, she emphasizes.

With this expanding array of treatment options, customization of treatment for patients becomes more feasible, allowing for a careful consideration of key factors, such as age, ECOG performance status, and smoking history, she continues. For instance, in cases of never smokers, the absence of a driver mutation might prompt the inclusion of chemotherapy alongside immune checkpoint inhibitors, ensuring a comprehensive treatment approach, Chiang elucidates.

The decision-making process is further influenced by patient preferences, necessitating thorough discussions, as well as practical considerations, such as drug availability andinsurance coverage. The administration frequency of each regimen is a particularly relevant aspect to consider because of administration adjustments made during the COVID-19 pandemic, according to Chiang. For example, when receiveing certain agents, some patients benefit from a shift to monthly administration from the conventional 3-week schedule, she concludes.