MD Anderson Research Highlights for the 2024 World Conference on Lung Cancer

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. This special edition features compelling data on lung cancer advances presented by MD Anderson researchers at the 2024 World Conference on Lung Cancer.

Targeted therapy before surgery may benefit patients with NSCLC

Adding immune checkpoint inhibitor durvalumab to perioperative (pre- and post-surgical) chemotherapy improves pathological complete response (pCR) and event-free survival in patients with non-small cell lung cancer (NSCLC) compared to chemotherapy alone. In the Phase II NeoCOAST-2 study, researchers led by Tina Cascone, examined novel combination treatments in patients with resectable Stage IIA-IIIB NSCLC.

Treatment arms included perioperative durvalumab plus chemotherapy in combination with an anti-CD73 antibody, an anti-NKG2A antibody, or a TROP2 antibody-drug conjugate (ADC). Higher rates of major pathological response (mPR) and/or pCR were seen in all arms compared to historical benchmarks.

Participants receiving TROP2 ADC had the highest mPR and pCR rates at 65.9% and 34.1%, respectively, highlighting the therapeutic potential of an ADC for neoadjuvant NSCLC. Treatments in all arms showed manageable safety profiles and surgical rates, comparable to current neoadjuvant and perioperative immunotherapy-based regimens.

Cross-trial analysis shows perioperative treatment improves NSCLC outcomes

The CheckMate 816 trial demonstrated that neoadjuvant (pre-surgical) nivolumab plus chemotherapy improves event-free survival (EFS) and pathological complete response (pCR) for patients with resectable non-small cell lung cancer (NSCLC), which is now the standard of care.

The Checkmate 77T trial built upon this, demonstrating improved EFS and pCR with perioperative (pre- and post-surgical) nivolumab compared to a placebo. In this analysis, researchers led by Tina Cascone, used data from both trials to examine the significance of perioperative nivolumab compared to neoadjuvant treatment.

They analyzed characteristics from 147 patients receiving neoadjuvant nivolumab and 139 patients receiving perioperative nivolumab. Perioperative nivolumab had significant improvements in EFS compared to neoadjuvant treatment in patients with resectable NSCLC, regardless of PD-L1 status, highlighting the importance of considering perioperative treatment for this patient population.

Oral treatment shows promise in HER2-mutant lung cancer 

Patients with advanced non-small cell lung cancers (NSCLCs) harboring specific HER2 mutations have limited effective treatment options. Given recent encouraging trial results, the Food and Drug Administration granted BAY 2927088 – an oral tyrosine kinase inhibitor targeting mutant HER2 – breakthrough therapy designation for pretreated patients with unresectable HER2-mutant NSCLC. In updated results of the Phase I/II SOHO-01 study, researchers led by Xiuning Le, examined the safety and efficacy of BAY 2927088 in 44 patients with advanced HER2-mutant NSCLC.

The treatment led to a rapid, substantial and durable response, with an objective response rate of 72.1%, including one complete response. Median duration of response and progression-free survival were 8.7 months and 7.5 months, respectively, with 16 out of 44 patients still receiving treatment after nearly 11 months. On the study, 95.5% of patients experienced drug-related, but manageable, side effects consistent with previous reports.

Zongertinib shows promising efficacy for HER2+ metastatic NSCLC

Zongertinib is an oral HER2-specific tyrosine kinase inhibitor that recently was granted fast track designation by the Food and Drug Administration for patients with advanced or metastatic HER2-positive non-small cell lung cancer (NSCLC) who did not respond to chemotherapy.

In the first-in-human Phase Ia Beamion LUNG-1 trial, researchers led by John Heymach, showed that zongertinib had promising overall response and disease control rates for patients with HER2-positive solid tumors and HER2-positive NSCLC. In the first cohort of Phase Ib, researchers administered either 120 mg or 240 mg of zongertinib to 132 pretreated patients with advanced HER2-positive metastatic NSCLC.

As of May 2024, the study met its primary endpoint, with an objective response rate of 66.7% and a disease control rate of 95.5% across all patients. While zongertinib was well-tolerated, most patients experienced manageable side effects, with 10 patients (7.6%) having serious adverse events and four patients (3.0%) having to discontinue treatment. The trial is ongoing and shows promising results for this patient population.

EGFR inhibitor effective for rare EGFR mutant non-small cell lung cancer

The Food and Drug Administration recently granted breakthrough therapy designation to firmonertinib – an oral, highly brain-penetrant EGFR inhibitor – for patients with advanced non-small cell lung cancer (NSCLC) harboring specific EGFR exon20 mutations.

In the Phase I/II FURTHER study, researchers led by Xiuning Le, investigated firmonertinib’s efficacy in 60 patients with NSCLC harboring P-loop and aC-helix compressing (PACC) mutations, which represent approximately 12% of EGFR mutations. The overall response rate, observed at two different dose levels, was 81.9% at 240 mg and 47.8% at 160 mg. The median duration of response hasn’t been determined yet, as 90.9% of patients with confirmed responses are still undergoing treatment.

Among 13 patients with brain metastases, six (46.2%) achieved an objective response. This study highlights the safety, efficacy and antitumor activity of firmonertinib across a broad range of EGFR PACC mutations, meriting further investigation.

Perioperative immunotherapy-based treatment yields improved outcomes

The global Phase III AEGEAN trial for patients with resectable non-small cell lung cancer (NSCLC) demonstrated that adding durvalumab – an anti-PD-L1 immune checkpoint inhibitor –to perioperative chemotherapy significantly improved event-free survival (EFS) and pathological complete response (pCR) rates compared to chemotherapy alone.

In updated results after 18 months of follow-up, researchers led by John Heymach, showed continued EFS benefit favoring the durvalumab arm, with clinically meaningful improvements in disease-free survival and overall survival. The risk of disease progression was 31% lower in the treatment group compared to the control group after a median follow-up of 25.9 months. Perioperative durvalumab plus neoadjuvant chemotherapy remained associated with a manageable safety profile.

Based on these results, the Food and Drug Administration approved the regimen in August 2024 as a new standard for resectable NSCLC.

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