Advancements in Lung Cancer Treatment: Insights from ASCO 2024

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Lung cancer remains a leading cause of cancer-related deaths worldwide. Advances in targeted therapies improving the outcome for lung cancer patients were highlighted at the ASCO 2024 conference. A summary of clinical data, focusing on novel treatment options and new combination therapies.

Primary Results of Sacituzumab govitecan or Adagrasib VS Docetaxel in Patients with Non-Small Cell Lung Cancer

Docetaxel (T) is one of the current second-line or later (2L+) treatment options for non-small cell lung cancer (NSCLC).¹ However, T outcomes remain poor, with patients tolerating side effects negatively.¹ Researchers from the EVOKE-01 (NCT05089734) study compared sacituzumab govitecan (SG) to T in patients with metastatic NSCLC (mNSCLC) who had previously received platinum-based chemotherapy (CTx) and PD-(L)1 inhibitors.¹ The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), patient-reported outcomes (PRO), and safety.¹ Patients (n=603) were randomised to receive either SG or T.¹ While the study did not meet statistical significance for OS, there was a numerical improvement in the median OS favouring SG vs T; 11.1 months vs 9.8 months, respectively (HR, 0.84; 95% CI, 0.68–1.04; 1-sided p=0.0534).¹ The study also revealed that SG improved PRO and was better tolerated than T, with a similar safety profile as observed in other studies with SG.¹

The KRYSTAL-12 trial (NCT04685135) compared adagrasib (ADA) to T in patients with KRAS^G12C-mutated locally advanced NSCLC (laNSCLC) or mNSCLC who had previously received platinum-based CTx and anti-PD-(L)1 therapy.² The primary endpoint was PFS, which was significantly improved with ADA compared to T (HR, 0.58; 95% CI, 0.45–0.76, p<0.0001).² The ORR by blinded review was also higher with ADA vs T measuring 31.9% vs 9.2% (OR, 4.68; 95% CI, 2.56–8.56; p<0.0001).² The median duration of response was 8.31 months for ADA vs 5.36 months for T.² Treatment-related adverse events were reported more frequently in patients treated with ADA (94.0%) than with T (86.4%), with grade ≥3 events occurring in 47.0% vs 45.7%, respectively.² The safety profile of ADA was consistent with previous reports and with no new safety signals.² These results support ADA as an efficacious treatment option for patients with previously treated KRAS^G12C-mutated laNSCLC and mNSCLC.²

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**Amivantamab plus Lazertinib VS Osimertinib in EGFR-Mutant Advanced Non-Small Cell Lung Cancer**

The MARIPOSA trial (NCT04487080) compared amivantamab plus lazertinib (AMI+LAZ) to osimertinib (OSI) as first-line (1L) treatment in 636 patients with epidermal growth factor receptor-mutant (EGFRm) advanced NSCLC (aNSCLC).³ AMI is an EGFR/MET-directed bispecific antibody with immune cell-activating properties, and LAZ is a central nervous system (CNS)-penetrant, 3rd-generation EGFR-directed tyrosine kinase inhibitor (TKI). This secondary analysis focused on the high-risk subgroups, including those with baseline liver and brain metastases, TP53 co-mutations, and detectable circulating tumour DNA (ctDNA).³ Results showed that AMI+LAZ significantly improved the PFS when compared to OSI in high-risk groups, with a median PFS (mPFS) of 18.2 months for AMI+LAZ vs 12.9 months for OSI (HR, 0.65; p=0.003).³ In patients with detectable ctDNA at baseline, AMI+LAZ treatment resulted in mPFS of 20.3 months vs 14.8 months in those receiving OSI (HR, 0.68; p=0.002).³ This result seemed less pronounced in patients clearing ctDNA at C3D1 (HR, 0.64; p=0.0004) than those who did not (HR, 0.48; p=0.014).³ Finally, in those patients with baseline liver metastases, the mPFS with AMI+LAZ was significantly longer when compared to OSI, measuring 18.2 months vs 11.0 months, respectively (HR, 0.58; p=0.017).³ Overall, AMI+LAZ demonstrated superior efficacy compared to OSI in high-risk patients with EGFRm aNSCLC.³

**Ivonescimab with Chemotherapy in EGFR-Mutant Non-Squamous Non-Small Cell Lung Cancer Patients**

The HARMONi-A trial (NCT05184712) evaluated the efficacy and safety of ivonescimab (IVO), an anti-PD-1/vascular endothelial growth receptor (VEGF) bispecific antibody, plus pemetrexed-carboplatin (CTx) vs placebo plus CTx alone in patients with non-squamous NSCLC who had failed prior EGFR-TKI treatment.⁴ The study randomised 322 patients to receive either IVO plus CTx or placebo with CTx.⁴ The primary endpoint was PFS. Results suggested that IVO significantly improved PFS compared to CTx alone, with a mPFS of 7.06 months vs 4.80 months, respectively (HR, 0.46; 95% CI, 0.34–0.62; p<0.0001).⁴ Notably, patients progressing on third-generation EGFR-TKI, patients with brain metastases, patients with EGFR exon 19 deletions, and those harbouring T790M point mutations all benefited from IVO treatment.⁴ IVO also demonstrated a higher ORR measuring 50.6% vs 35.4% with CTx alone.⁴ Overall, IVO plus CTx showed a manageable safety profile and improved PFS in patients who had progressed on prior EGFR-TKI treatment.⁴

References

Paz-Ares LG, et al. J Clin Oncol. 2024;42(17_suppl):LBA8500.

Mok TSK, et al. J Clin Oncol. 2024;42(17_suppl):LBA8509.

Felip E, et al. J Clin Oncol. 2024;42(16_suppl):8504.

Zhang L, et al. J Clin Oncol. 2024;42(16_suppl):8508.

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).