Defining the Role of Perioperative Therapy Across Lung Cancer Subtypes

Attaining a complete response (CR) with neoadjuvant therapy among patients with lung cancer may reduce the need for adjuvant therapy, according to Girindra Raval, MD. Raval discussed the role of perioperative therapy among patients undergoing treatment for lung cancer as part of an interview with CancerNetwork® in a visit to Georgia Cancer Center.

He began by highlighting trials evaluating osimertinib (Tagrisso) in the neoadjuvant and adjuvant setting; the phase 3 NeoADAURA (NCT04351555) and ADAURA trials (NCT02511106) trials, respectively.^1,2 Then, he touched upon the phase 3 ALINA trial (NCT03456076), in which alectinib (Alecensa), an ALK inhibitor, displayed favorable efficacy vs chemotherapy among patients with ALK-positive non–small cell lung cancer (NSCLC).³ Additionally, Raval highlighted trials evaluating adjuvant early-stage diseases across numerous targets that are still awaiting data read outs.

Regarding patients without targetable mutations, he identified numerous trials assessing perioperative immunotherapy in lung cancer: the phase 3 KEYNOTE-671 trial (NCT03425643) assessing pembrolizumab (Keytruda); the phase 3 CheckMate 77T trial (NCT04025879) assessing nivolumab (Opdivo), and the phase 3 AEGEAN trial (NCT03800134) assessing durvalumab (Imfinzi).^4-6 Lastly, he touched upon the phase 3 CheckMate 816 trial (NCT02998528), which displayed the benefit of adding neoadjuvant nivolumab to chemotherapy.⁷

Raval, an associate professor of the Department of Medicine: Hematology and Oncology at the Medical College of Georgia at Augusta University, concluded by emphasizing that adjuvant therapy may not benefit patients who have attained a CR with neoadjuvant treatment.

Transcript:

There are data for neoadjuvant osimertinib; hopefully, we will get the results read out soon with the NeoADAURA trial. There’s a category 1 recommendation for adjuvant osimertinib based on the ADAURA trial. Then, there are the ALK inhibitors, where we have data about adjuvant alectinib based on the ALINA trial that was done recently. This is the part in the early-stage curative setting with the targets. There are other trials underway in the early-stage setting with patients who have RET mutations, ROS1 mutations, and exon 20 insertion mutations as well; we are waiting for the results of those trials to be read out.

For patients who do not have targets, there is a plethora of data based on the KEYNOTE-671, CheckMate 77T, and the AEGEAN studies about the use of perioperative immunotherapy in this space. We have been early adopters, thanks to our coordination with our surgical colleagues, to get these patients on the right therapy from the get-go. That usually translates, at our institution, with the neoadjuvant trial, CheckMate 816, which has shown an overall survival benefit after 3 to 4 cycles of neoadjuvant treatment. There, we have good data that if the patients develop a complete response, they do not need any adjuvant immunotherapy afterwards.

Most of the trials and most of the therapy that we give now, based on the state of the field, are tailored according to what we find at the time of surgery, after the patients have received neoadjuvant chemoimmunotherapy. These patients would then, if they have developed a [pathological] CR, probably not benefit from receiving any further adjuvant treatment. If they did not, there is a role for continuing nivolumab, pembrolizumab, or durvalumab based on the trials that we have read out so far.

References

1. He J, Tsuboi M, Weder W, et al. Neoadjuvant osimertinib for resectable EGFR-mutated non–small cell lung cancer. J Clin Oncol. 2025;43(26):2875-2887. Doi:10.1200/JCO-25-00883
2. Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non–small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071
3. Wu Y-L, Dziadziuszko R, Ahn JS, et al. Alectinib in resected ALK-positive non–small-cell lung cancer. N Engl J Med. 2024;390(14):1265-1276. doi:10.1056/NEJMoa2310532
4. Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non–small-cell lung cancer. N Engl J Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983
5. Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med. 2024;390(19):1756-1769. doi: 10.1056/NEJMoa2311926
6. Heymach JV, Harpole D, Mitsudomi, et al. Perioperative durvalumab for resectable non–small-cell lung cancer. N Engl J Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875
7. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170