Exploring the Perioperative Treatment Setting in Lung Cancer

Treatment strategies in early-stage lung cancers will be a focus of the 19th Annual New York Lung Cancers Symposium® to be held November 16, 2024, and led by cochairs Balazs Halmos, MD, MS and Mark G. Kris, MD. In an interview with Targeted Therapies in Oncology prior to the conference, Kris addressed the emerging role of immune checkpoint inhibitors in the perioperative space based on findings from the CheckMate 816 (NCT02998528), IMpower010 (NCT02486718), PEARLS (NCT02504372), and ADAURA (NCT02511106) trials.

“In the perioperative setting we have data from several randomized trials showing that neoadjuvant immunotherapy with chemotherapy have a benefit over chemotherapy alone,” Kris, the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, said.

CheckMate 816

Findings from the phase 3 CheckMate 816 trial led the FDA to approve nivolumab (Opdivo), making it the first neoadjuvant immunotherapy Mark G. Kris, MD William and Joy Ruane Chair in Thoracic Oncology Memorial Sloan Kettering Cancer Center New York, NY indicated for early-stage non–small cell lung cancer (NSCLC).¹

Investigators reported a median event-free survival (EFS) of 31.6 months (95% CI, 30.2-not reached) for patients who received the combination of nivolumab plus chemotherapy compared with 20.8 months (95% CI, 14.0-26.7) for patients who received chemotherapy alone.² Patients in the treatment arm (n = 179) demonstrated a pathological complete response (pCR) of 24.0% (95% CI, 18.0% -31.0%) compared with 2.2% (95% CI, 0.6%-5.6%) for patients in the control arm (n = 179; OR, 13.94; 99% CI, 3.49%-55.8%; P < .001). For most subgroups, patients who received the combination had favorable EFS and pCR over patients who received the monotherapy.

Using immunotherapy in in this setting provides an opportunity to treat micrometastatic disease at diagnosis and enhances the immune response.³

Much of Kris’s focus is in the perioperative space. “The findings using checkpoint inhibitors given before surgery were unexpected and amazing. I urge physicians who treat patients with early-stage lung cancer to consider neoadjuvant immunotherapy with chemotherapy,” Kris said.

ASCO Annual Meeting

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, effective sequencing of treatments was also explored. Findings from the LAURA trial (NCT03521154) demonstrated the benefit of giving osimertinib (Tagrisso) after definitive chemoradiotherapy in progression-free survival (PFS) in patients with locally advanced, unresectable, stage III NSCLC, particularly in patients whose tumor harbors an EGFR mutation.⁴

“The question about what is the best treatment after concurrent chemotherapy and radiation was addressed by findings from the LAURA trial,” Kris said. “For patients with tumors that harbor EGFR mutations, giving osimertinib after definitive chemoradiotherapy improves disease-free survival and overall survival [OS]. This approach will replace durvalumab in these patients,” Kris added.

The agent reduced the risk of progression or death by 84% compared with placebo (HR, 0.16; 95% CI, 0.10-0.24; P < .001). Patients treated with osimertinib (n = 143) experienced a median PFS of 39.1 months (95% CI, 31.5- not calculable) vs 5.6 months (95% CI, 3.7-7.4) for patients who received placebo (n = 73).

The 12-month PFS rate for patients in the osimertinib arm was 74% vs 22% in the control arm. Similarly, the 24-month PFS rate was favored for patients in the osimertinib arm at 65% vs 13% for patients in the control arm.

Although durvalumab (Imfinzi) is the standard of care following chemoradiotherapy in patients with unresectable stage III NSCLC, patients with tumors with EGFR mutations are particularly vulnerable as the benefit of durvalumab is marginal at best, according to findings from the PACIFIC trial (NCT02125461). In that trial, durvalumab did not show a significant improvement in PFS compared with placebo in patients with EGFR-mutated disease (HR, 0.91; 95% CI, 0.39-2.13).⁵

In the LAURA trial, patients were randomly assigned 2:1 to receive either 80 mg of osimertinib or placebo once per day. Treatment continued until blinded independent central review (BICR)–assessed disease progression per RECIST 1.1 criteria, unacceptable toxicity, or other discontinuation criteria were met.

Notably, patients in both arms were permitted to receive open-label osimertinib following BICR-confirmed disease progression. Tumor assessments were conducted via chest CT/MRI and brain MRI at baseline, then once every 8 weeks until week 48, then once every 12 weeks thereafter until BICR-confirmed progression.

Another major presentation during the 2024 ASCO Annual Meeting featured findings from the ADRIATIC study (NCT03703297)6 that looked at durvalumab as consolidation therapy for patients with limited-stage small cell lung cancer (SCLC). Durvalumab significantly improved OS and PFS over standard chemoradiotherapy. Patients were randomly assigned to receive either durvalumab with placebo, durvalumab with tremelimumab (Imjudo), or placebo alone.

These findings suggest a promising new treatment option for patients with this disease.

New York Lung Cancers Symposium

Providing a comprehensive overview with a focus on multidisciplinary lung cancer treatment, 2 characteristics make the conference unique (AGENDA).

“We work hard to make this a very interactive meeting. It is geared toward practitioners, but we call upon researchers to present the most up-to-date data to the oncologists on the front lines,” Kris said. “It is not a dry data review. For people who attend the conference, they will walk away with expert opinion, and not just a list of possible treatment solutions,” continued Kris.

The other characteristic about the conference is that it draws practitioners from all over the New York/New Jersey/Connecticut area. It will include data important to advanced practice practitioners, physician assistants, trainees, residents, and fellows. “We try very hard to have good representation of all kinds of specialists in lung cancer,” Kris said.

Turning to the agenda, Kris said the presentation by Zosia Piotrowska, MD, MHS, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, called “The Other EGFRs: Exon 20 Insertions and More,” will focus “on the rarer EGFR mutations and exon 20 and the next- generation agents that will soon be available.”

The afternoon session will focus on the practicality of caring for patients with lung cancers, with a spotlight on the appropriate timing for genetic testing results. The presentation will be delivered by Gregory J. Riely, MD, PhD, the Ning Zhao and Ge Li Chair in Lung Cancer Research at Memorial Sloan Kettering Cancer Center in New York, New York.

Regarding next-generation sequencing (NGS), the importance of those findings cannot be emphasized enough, according to Kris.

“Even if the disease involves squamous cells, even if the clinician isn’t sure what cell type the cancer is, it’s important to order NGS testing, because it can open up other avenues of treatment for the clinician given the number of targetable drivers that can be identified,” Kris said.

REFERENCES:

1. FDA approves neoadjuvant nivolumab and platinum-doublet chemotherapy for early-stage non-small cell lung cancer. FDA. March 4, 2022. Accessed September 11, 2024. https://tinyurl.com/bdcndyut

2. 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

3. Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science. 2020;367(6477):eaax0182. doi:10.1126/science.aax0182

4. Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. J Clin Oncol. 2024;42(suppl 17):LBA4. doi:10.1200/JCO.2024.42.17_suppl.LBA4

5. Naidoo J, Antonia S, Wu YL, et al. Brief report: durvalumab after chemoradiotherapy in unresectable stage III EGFR-mutant NSCLC: a post hoc subgroup analysis from PACIFIC. J Thorac Oncol. 2023;18(5):657-663. doi:10.1016/j. jtho.2023.02.009

6. Spigel D, Cheng Y, Cho B, et al. ADRIATIC: durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol. 2024;42 (suppl 17):LBA5. doi:10.1200/JCO.2024.42.17_ suppl.LBA5) doi:10.1200/JCO.2024.42.17_suppl.LBA5