Lung cancer news

Lung cancer news

Background

We have selected some news of the last two months related to lung cancer, published online in Medscape, Cancer Connect and IASLC. We note both the emergence of new compounds in the therapy of advanced cases and new indications for compounds already included in the current therapy of lung cancer.

1. “The FDA has granted accelerated ap­proval to telisotuzumab vedotin-tllv (Emrelis®) as a treatment for adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) and high c-MET protein expression previously managed with systemic therapy”⁽¹⁾, according to a press release from the developer, AbbVie.

With this decision, telisotuzumab vedotin is the first and only available therapy for this NSCLC subtype.

The agency based its decision on data from the phase 2 LUMINOSITY trial (NCT03539536), in which investigators assessed the agent as a treatment for those with previously treated c-MET-positive NSCLC.

Topline data revealed an overall response rate (ORR) of 35% (95% CI; 24-46%) and a median duration of response (DOR) of 7.2 months (95% CI; 4.2-12) among 84 evaluable patients with high c-MET protein overexpression. According to the FDA, continued approval for telisotuzumab vedotin may be dependent on additional validation of the agent’s clinical benefit in a confirmatory trial.

“We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes. People with c-MET-overexpressing NSCLC have poor prognosis and limited treatment options, and [telisotuzumab vedotin] is a first-in-class antibody drug conjugate (ADC) that can address a critical unmet need for this patient population”⁽¹⁾, said Jonathan Goldman (MD), professor of medicine and director of Thoracic Oncology Clinical Trials at the University of California, Los Angeles, in the press release.

Safety data showed that the most common adverse effects (AEs) associated with the therapy included peripheral neuropathy, fatigue, diminished appetite and peripheral edema. Additionally, grade 3/4 laboratory abnormalities included decreased lymphocytes, increased glucose, increased ala­nine aminotransferase and elevated gamma-glutamyltransferase.

The FDA previously granted breakthrough therapy designation to telisotuzumab vedotin for this patient population in January 2022.

“[Telisotuzumab vedotin], AbbVie’s first internally developed solid tumor medicine and our first solid tumor FDA approval in lung cancer, is a testament to our commitment to develop cancer therapies that aim to improve the course of treatment for patients facing this challenging disease. Leveraging advanced technology and data science, we are growing our ADC portfolio designed to deliver the right medicines to the right patients in need across a range of difficult-to-treat tumors”, concluded Roopal Thakkar (MD), Executive Vice-President of Research and Development and Chief Scientific Officer at AbbVie”⁽¹⁾.

2. Beamion LUNG-01 trial results support zongertinib’s potential as a first-line therapy

Dr. John V. Heymach said that the latest findings suggest that zongertinib may address an unmet need for patients with HER2-mutant NSCLC.

Activating HER2 mutations occur in 2% to 4% of patients with non-small cell lung cancer (NSCLC). Patients harboring such mutations often have a worse prognosis and higher incidence of brain metastases.

“There remains a clear, unmet need for a potent TKI that selectively inhibits HER2 while sparing these EGFR-related toxicities”⁽²⁾, said John V. Heymach (MD, PhD), Chair of Thoracic, Head and Neck Medical Oncology and Professor at the University of Texas, MD Anderson Cancer Center.

Historically, it’s been a challenge to de­ve­­lop TKIs for HER2 mutations because of EGFR-related toxicities and structural changes that prevent drugs from effectively tar­ge­ting mutant HER2 kinase. Thus, until recently, treatment options have been limited for patients with HER2-mutant NSCLC. However, the latest results from the Beamion LUNG-1 trial suggest that research may have found a way to address current limitations with the novel TKI zongertinib.

The findings demonstrated a 71% objective response rate (ORR) in patients with tyrosine kinase domain (TKD) mutations and a 48% ORR in patients who had prior HER2-directed antibody drug conjugates (ADCs).

“Compared to drugs that have previously been tested in this space such as poziotinib and afatinib, zongertinib is roughly two orders of magnitude more selective for the HER2 insertion”⁽²⁾, added Dr. Heymach.

“The results were presented during the 2025 American Association for Cancer Research (AACR) Annual Meeting. Zongertinib, a potent covalent TKI, selectively inhibits HER2 while sparing wild-type EGFR. It has already received priority review from the US Food and Drug Administration for the treatment of unresectable or metastatic NSCLC.

In the phase Ib Beamion LUNG-1 interim analysis, a 120 mg daily dose was administered following the phase Ia dose escalation. The second part of the study enrolled participants from three cohorts:

• Cohort one, the primary and largest cohort, included patients with TKD mutations in a specific HER2 region.
• Cohort five included patients with TKD mutations who had previously received a HER2-directed ADC.
• Cohort three included patients with non-TKD mutations.

The primary endpoint was ORR as assessed by a blinded independent central review for cohorts one and five, or by investigator review for cohort three. The secondary endpoints included duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS). Dr. Heymach presented the efficacy and safety data as of the data cutoff of November 2024.

He said that responses to zongertinib were durable, with a median DoR of 14.1 months and a median time to response of 1.4 months. The median PFS for cohort one was 12.4 months. Zongertinib demonstra­ted intracranial activity in participants, with 81% of participants with brain metastases achieving disease control.

Additionally, zongertinib exhibited a manageable safety profile, with a low incidence of grade 3 treatment-related adverse events (TRAEs). Only 7% of participants experienced adverse events (AEs) that led to a dose reduction, and only 3% discontinued the treatment due to AEs.”⁽²⁾

“Most drug-related adverse events were grade 1 and 2”, added Dr. Heymach. “The most common AE was diarrhea, which was largely grade 1. Only one patient had grade 3 diarrhea.

With a favorable safety profile and strong response rates, the Beamion LUNG-01 trial sets the stage for zongertinib as a potential first-line therapy for patients with HER2-mutant NSCLC.

The Beamion LUNG-02 trial is underway and will evaluate the efficacy and safety of zongertinib compared with pembrolizumab in combination with platinum-pemetrexed chemotherapy”⁽²⁾.

3. Advancing the needle on the management of resectable EGFR-positive NSCLC: is neoadjuvant osimertinib the answer?

“In summary, the authors of NORA should be commended for their efforts in evaluating the role of perioperative osimertinib. Although much progress has been made in improving treatment outcomes for patients with early-stage EGFR-mutant NSCLC, several unanswered questions remain, including whether TKI alone is sufficient for cure. Given the rapid advancements in the metastatic setting with the incorporation of novel agents such as amivantamab and antibody-drug conjugates, it is conceivable that these compounds will be introduced in the earlier stage setting for EGFR mutant NSCLC. Yet, it is not practical to conduct multiple phase III trials powered for overall survival to evaluate each of these combinations, given the swiftly evolving treatment landscape. To that end, future trials should interrogate the robustness of earlier endpoints such as pathologic response as a surrogate for survival in the context of TKI, and explore adaptive trial designs based on pathologic or ctDNA response to refine risk stratification approaches”⁽³⁾.

4. Extensive-stage small cell lung cancer: real-world comparison of atezolizumab (Techntriq®) versus durvalumab (Imfinzi®)

A real-world study indicates that durvalumab seemed to help patients live longer and might have fewer side effects than atezolizumab.

“In a recent real-world comparison study, researchers retrospectively analyzed data from patients with extensive-stage small cell lung cancer to evaluate efficacy and safety of atezolizumab versus durvalumab. A real-world comparison study is a type of research that looks at how cancer treatments work in everyday medical practice, outside of the controlled environment of clinical trials.

Key findings: patients who received durvalumab lived longer on average. Those on durvalumab lived about 14.7 months, while those on atezolizumab lived about 11.6 months. Fewer patients on durvalumab experienced immune-related side effects compared to those on atezolizumab (about 33% versus 48%); however, this finding was not statistically significant. Also, fewer durvalumab patients needed to be hospitalized due to these side effects (about 17% versus 36%)”.⁽⁴⁾

5. Non-small cell lung cancer: what you need to know about ctDNA testing

“Medicare has expanded coverage for a ctDNA test, a personalized molecular residual disease (MRD) test, to include patients with stage I-III non-small cell lung cancer (NSCLC) in the surveillance setting. This means that both resectable and unresectable NSCLC patients can now access ctDNA testing under Medicare for ongoing monitoring after diagnosis or treatment. This coverage builds on existing Medicare approval for using ctDNA to monitor immunotherapy, a common treatment for NSCLC in both early and advanced stages.

Why this matters for lung cancer patients:

• Earlier detection of recurrence – ctDNA uses a blood sample to detect circulating tumor DNA, allowing it to identify cancer recurrence up to a year before it would appear on imaging scans (median lead time: five months). This can give doctors and patients a crucial head start in managing the disease.
• High accuracy – in three independent peer-reviewed studies, ctDNA with Signatera’s test demonstrated a sensitivity of 93-100% and a specificity of 96-100% for detecting extracranial recurrence in NSCLC patients.
• Addresses gaps in current surveil­lance – traditional surveillance tools like CT scans can be difficult to interpret and may miss early signs of recurrence. ctDNA offers a more sensitive and specific option to support early intervention, potentially improving outcomes.”⁽⁵⁾

6. European Lung Cancer Conference (ELCC) 2025, March 26-29, 2025, Paris, France

‘Take a Photograph’: Trial Shows Big Survival Gain in Advanced EGFR-Mutant NSCLC

“Final overall survival results from the phase 3 MARIPOSA study showed that the first-line amivantamab plus lazertinib combination extended overall survival notably more than osimertinib in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)”.⁽⁶⁾

7. Osimertinib OS benefit per­sists among patients with EGFR+NSCLC

“Osimertinib (Tagrisso®, AstraZeneca) continues to provide an overall survival (OS) benefit after definitive chemoradiotherapy (CRT) in patients with unresectable stage III epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), according to the latest results from the pivotal phase 3 LAURA study. [...] This updated analysis [...] demonstrates an improved favorable trend for overall survival benefit with osimertinib over placebo”⁽⁷⁾, reported lead investigator Suresh Ramalingam (MD) at the European Lung Cancer Congress 2025.

8. Skin care regimen cuts toxicities of combination NSCLC therapy

“An enhanced prophylactic regimen using widely available and easy-to-use agents significantly reduced the incidence and severity of dermatologic reactions associated with first-line amivantamab plus lazertinib in epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC), early data from the COCOON trial showed.

Compared with standard-of-care dermatologic management, the enhanced prophylactic skin regimen led to significant reductions in grade 2 or higher dermatologic adverse events (AEs) and allowed more patients to stay on cancer treatment without dose interruption, reduction, or discontinuation.

With the overall survival benefits seen with amivantamab plus lazertinib in MARIPOSA, we expect more patients to receive this combination, and the COCOON regimen should really be implemented in clinical practice to improve the patient experience”⁽⁸⁾, said Nicolas Girard (MD), PhD, Head of Medical Oncology at Institute Curie, in Paris, France.

“Standard-of-care dermatologic management included general skin prophylaxis per local practice and reactive treatment, such as topical steroids and systemic antibiotics.

In contrast, enhanced management included an oral antibiotic (100 mg doxycycline or minocycline) administered twice daily for 12 weeks, followed by a topical antibiotic (1% clindamycin) applied to the scalp, an antibacterial wash (4% chlorhexidine) on the nails, and a ceramide-based moisturizer applied once daily to the body and face”.⁽⁸⁾

9. Subcutaneous pembrolizumab on par with i.v. administration in lung cancer

“For patients with metastatic non-small cell lung cancer (NSCLC), subcutaneous (s.c.) administration of pembrolizumab works just as well as standard intravenous (i.v.) administration, phase 3 data indicated.

The open-label, phase 3 MK-3475A-D77 trial enrolled 377 pa­tients with newly diagnosed stage IV NSCLC without sensitizing genetic mutations. They were randomly allocated (2:1) to first-line treatment with pembrolizumab SC (790 mg) or pembrolizumab i.v. (400 mg) every six weeks in addition to platinum doublet chemotherapy.

The study met its dual primary pharmacokinetic endpoints of area under the curve (AUC) of pembrolizumab exposure during the first dosing cycle (0-6 weeks) and steady-state (cycle 3) trough concentration”⁽⁹⁾.

In conclusion, although no therapeutic means have been discovered that would radically change the evolution of lung cancer, there is still an evolution of therapeutic means that has resulted in increased survival. The determination of ctDNA represents a new standard for monitoring the disease that would be useful if it were reimbursed. However, all the evolution of treatments and investigations means is increasingly raising costs and perhaps there should be better cooperation between economists and the pharmaceutical industry, between research doctors and the pharmaceutical industry, for conducting studies and at the proposal of research investigators for pertinent comparisons within clinical trials. Also, each country must adopt the best financing plan for newly emerging drugs, a plan prioritized after consultation of decision-makers with research doctors in real cooperation.