Advancements in aNSCLC Treatment: Highlights from WCLC 2024 – Medical News Asia

Non-Sponsored Content

ONCOLOGY

Advancements in advanced NSCLC Treatment: Highlights from WCLC 2024

Medical writer: Adiya Ualiyeva | Last updated: 17 September 2024 | In: Lung Cancer, Oncology

Article Keywords

lung cancer, amivantamab, non-small cell lung cancer, ivonescimab, EGFR mutations

Lung cancer continues to be a leading cause of cancer-related deaths in Hong Kong, with non-small cell lung cancer (NSCLC) accounting for about 82% of cases in 2021.¹ Recent findings from the World Conference on Lung Cancer (WCLC) 2024, highlight promising advancements in the treatment of advanced NSCLC (aNSCLC).²

HARMONi-2 Study: Ivonescimab vs Pembrolizumab in PD-L1-positive NSCLC

A total of 398 patients with untreated locally advanced or metastatic NSCLC (defined as Eastern Cooperative Oncology Group performance status [ECOG PS] 0–1, programmed death ligand 1 [PD-L1]-positive but negative epidermal growth factor receptor [EGFR] mutations or ALK rearrangement) in China were randomised 1:1 to receive either ivonescimab (IVO) (n=198) or pembrolizumab (PEMBRO) (n=200) in the recent Phase 3 HARMONi-2 study (NCT05499390).³ The primary endpoint was progression-free survival (PFS) by blinded independent radiographic review committee (IRRC) per RECIST v1.1.³

Notably, IVO extended median PFS to 11.14 months, a marked improvement over PEMBRO’s 5.82 months (stratified HR=0.51; p<0.0001).³ Consistent PFS benefit of IVO over PEMBRO was observed across various subgroups, including squamous NSCLC (HR=0.50), non-squamous NSCLC (HR=0.55), with tumour proportion score (TPS) 1–49% (HR=0.54), and TPS ≥50% (HR=0.48), as well as liver (HR=0.47) and brain metastases (HR=0.55).³ Regarding safety, no new safety signals were identified with IVO.³ Treatment-related serious adverse events (TRSAEs) occurred in 20.8% of patients on the IVO arm and 16.1% on the PEMBRO arm, while grade ≥3 immune-related adverse events were reported in 7.1% and 8.0%, respectively.³ IVO showed a particularly manageable safety profile in patients with squamous cell carcinoma, with comparable TRSAEs in both arms (IVO: 18.9% vs PEMBRO: 18.7%).³

These results support IVO monotherapy as a potential new first-line treatment option for PD-L1-positive aNSCLC patients, offering statistically significant and clinically meaningful improvement in PFS compared to PEMBRO, along with a manageable safety profile.³

At the Heart of the Discussion: COVID-19 Cardiovascular Complications in Pregnant Women

Vaccination versus Active Infection: A Comparison of the Cardiovascular Risks

Common Respiratory Viruses and Their Associated Cardiovascular Risks

Personalised Angina Treatment at Cellular Level

Previous Next

At the Heart of the Discussion: COVID-19 Cardiovascular Complications in the Pregnant Women

6 November 2022

At the Heart of the Discussion: COVID-19 Cardiovascular Complications in Pregnant Women

26 August 2022

Vaccination versus Active Infection: A Comparison of the Cardiovascular Risks

PAPILLON: TP53 Co-mutations, Sites of Insertion and ctDNA Clearance Among Patients with EGFR Ex20ins-mutated aNSCLC

The PAPILLON study (NCT04538664) evaluated the efficacy of amivantamab (AMI), an EGFR-MET bispecific antibody, combined with carboplatin-pemetrexed chemotherapy (cTx) for treating aNSCLC with EGFR Exon 20 insertions (Ex20ins). A total of 308 patients were randomised to receive either AMI-cTx (n=153) or cTx alone (n=155).⁴ TP53 co-mutation and detectable circulating tumour DNA (ctDNA) are associated with poor prognoses.⁴ This analysis specifically assessed treatment outcomes among patients from PAPILLON by biomarker subgroups, including TP53 co-mutations and ctDNA status.⁴

Among patients with analysable ctDNA at baseline (n=206), 86% had detectable pathogenic alterations and of these 58% (n=104/178) had TP53 co-mutations.⁴ In patients with detectable baseline ctDNA, AMI-cTx significantly improved PFS vs cTx (11.1 vs 5.8 months; HR=0.38; p<0.0001).⁴ Additionally, more patients in the AMI-cTx arm cleared Ex20ins ctDNA by Cycle 3 Day 1 (69% vs 45%) than the cTx arm. The PFS was nearly doubled with AMI-cTx in patients with ctDNA clearance (12.2 vs 6.8 months; HR=0.26; p<0.0001) and without (9.8 vs 4.8 months; HR=0.55 ) vs cTx alone.⁴

The PFS was significantly longer with AMI-cTx vs cTx regardless of the presence of TP53 co-mutation, with 11.1 vs 5.6 months (HR=0.29; p<0.0001) in patients with TP53 co-mutations and 11.3 vs 8.5 months (HR=0.45; p=0.008) in those with wildtype TP53.⁴ Objective response rates (ORR) were higher with AMI-cTx vs cTx for TP53 co-mutations (80% vs 53%; p=0.006) and wild-type TP53 (74% vs 49%; p=0.029).⁴ Duration of response (DoR) also prolonged in AMI-cTx vs cTx, in patients with TP53 co-mutations (9.8 vs 4.3 months) and wild-type TP53 (8.2 vs 4.6 months).⁴

Further analysis of EGFR Ex20ins sites (n=238) revealed a distribution of 83% in the near loop, 13% in the far loop, and 5% in the helical region.⁴ Remarkably, AMI-cTx demonstrated PFS benefits across all insertion sites, with significant improvements in both near loop (11.3 vs 5.8 months; HR=0.40; p<0.0001) and far loop regions (9.4 vs 4.1 months; HR=0.19; p=0.005), and a favourable trend in the helical region despite limited patient numbers.⁴ The ORR and DoR favoured AMI-cTx across Ex20ins sites.⁴

In conclusion, AMI plus cTx is the first-line standard-of-care for EGFR Ex20ins-mutated aNSCLC with superior outcomes over cTx alone in patients with and without biomarkers of high-risk disease.⁴

MARIPOSA Study: Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant aNSCLC in Longer Follow-up

The MARIPOSA study (NCT04487080) evaluated the efficacy of combining AMI with lazertinib (LAZ), a central nervous system-penetrant EGFR tyrosine kinase inhibitor, against osimertinib (OSI) in treatment-naïve, EGFR-mutated (Exon 19 deletions or Exon 21 L858R substitutions) locally advanced or metastatic NSCLC in 1,074 patients, with 429 in the open-label AMI-LAZ, 429 in blinded OSI and 216 in blinded LAZ alone.⁵ This analysis compared AMI-LAZ with OSI on post-progression outcomes and overall survival (OS).⁵

With a median follow-up of 31.1 months, 44% (185/421) of patients in the AMI-LAZ arm and 34% (145/428) in the OSI arm were still on treatment.⁵ Discontinuation due to disease progression occurred in 155 patients on AMI-LAZ and 233 on OSI, with 72% and 74% of these patients, respectively, starting subsequent therapy.⁵ The most common follow-up treatment was carboplatin-pemetrexed.⁵ PFS after the first subsequent therapy (PFS2) favoured the AMI-LAZ arm (HR=0.73; p=0.004).⁵ AMI-LAZ also resulted in longer median time to treatment discontinuation (26.3 vs 22.6 months), time to subsequent therapy (30.0 vs 24.0 months), as well as more favourable intracranial PFS trends (24.9 vs 22.2 months) vs OSI.⁵

While median OS was not fully estimable for AMI-LAZ, it showed a positive trend over OSI (HR=0.77; p=0.019).⁵ At 24 months, survival rates were 75% for AMI-LAZ and 70% for OSI, with 36-month rates at 61% and 53%, respectively.⁵

These results reaffirm AMI-LAZ as a first-line standard-of-care for EGFR-mutated aNSCLC.

References

Hong Kong Cancer Registry, Hospital Authority. Available online. https://www3.ha.org.hk/cancereg/pdf/factsheet/2021/lung_2021.pdf. Last accessed: 16 September 2024.

World Conference on Lung Cancer. Available online. https://cattendee.abstractsonline.com/meeting/20598/meeting-info?view=appendToCards&initialSearchId=1&searchId=1. Last accessed: 16 September 2024.

International Association for the Study of Lung Cancer (IASLC). WCLC 2024: Full Conference Abstract Book. [PL02.04]. Available online. https://wclc2024.iaslc.org/wp-content/uploads/2024/09/WCLC-2024-Full-Conference-Abstract-Book.pdf. Last accessed: 16 September 2024.

International Association for the Study of Lung Cancer (IASLC). WCLC 2024: Full Conference Abstract Book. [MA12.06]. Available online. https://wclc2024.iaslc.org/wp-content/uploads/2024/09/WCLC-2024-Full-Conference-Abstract-Book.pdf. Last accessed: 16 September 2024.

International Association for the Study of Lung Cancer (IASLC). WCLC 2024: Full Conference Abstract Book. [OA02.03]. Available online. https://wclc2024.iaslc.org/wp-content/uploads/2024/09/WCLC-2024-Full-Conference-Abstract-Book.pdf. Last accessed: 16 September 2024.

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).