Osimertinib Improves Survival in Lung Cancer
NY Senate Passes Bill To Expand Free Lung Cancer Screenings; Assembly Vote Pending
Senator Joseph Addabbo's bill on mandating health insurance for lung cancer has been approved by the Senate.
via Getty Images
The New York State Senate has unanimously passed Senate Bill S. 2000, a significant step toward improving the early detection and treatment of lung cancer in New York.
The bill is sponsored by Senator Joseph Addabbo who represents the Senate's 15th District, which includes the neighborhoods of Glendale, Middle Village, Ridgewood, Woodhaven. It mandates that health insurance providers cover follow-up screening and diagnostic services for lung cancer without any patient cost-sharing.
This legislation is designed to address a critical gap in healthcare coverage and remove the financial barriers that often prevent patients from accessing necessary follow-up tests.
Lung cancer continues to be one of the most common and deadly cancers in New York, and the statistics are startling. Every year, over 6,700 men and 7,200 women are diagnosed with lung cancer in the state. Tragically, approximately 3,800 men and 3,600 women succumb to the disease annually.
Despite the prevalence of lung cancer, early detection remains a challenge because symptoms of the disease typically do not appear until it has reached an advanced stage. At this point, treatment options are limited, and survival rates decrease dramatically.
The effectiveness of lung cancer screening in detecting the disease in its early stages is well-documented. However, a major barrier to utilizing these life-saving screenings is the financial burden that many patients face. Despite being eligible for screening, only about 19.5% of those recommended for testing actually undergo the procedure.
One primary reason for this low participation rate is the cost-sharing requirements associated with health insurance plans. Co-pays, co-insurance, and deductibles all create financial obstacles for individuals who might otherwise seek out screenings that could detect cancer early and increase their chances of survival.
Addabbo's bill seeks to eliminate these financial barriers by ensuring that follow-up screenings and diagnostic services for lung cancer are fully covered by insurance without any out-of-pocket costs for the patient.
This change is expected to significantly increase the number of individuals who seek early screening, leading to more diagnoses at treatable stages and ultimately saving lives.
"Far too many people are impacted by cancer, either personally or through a close relative or friend. I'm proud to make early detection screening and treatment available to everyone, especially those who would otherwise avoid these important tools, due to the cost," said Addabbo.
"An individual's health is one of the most precious things affecting your physical, mental, and emotional well-being. That's why it's so important to be proactive about your health and take appropriate actions to prevent illness and disease."
The bill received bipartisan support in the Senate, highlighting the widespread agreement on the importance of improving lung cancer detection and treatment in New York.
In addition to legislative backing, advocacy groups such as the American Cancer Society Cancer Action Network (ACS CAN) have lent their full support to the bill, recognizing the critical need for early detection and affordable treatment options.
Updated Trial Results Support Tagrisso As Standard-of-Care For EGFR-Mutated Lung Cancer
Results from multiple clinical trials showed that Tagrisso demonstrated survival benefits in EGFR-mutated non-small cell lung cancer, both as monotherapy and in combination therapies.
Image Credit: Adobe Stock Images/Sebastian Kaulitzki
Results from the Phase III LAURA and FLAURA2 trials and Phase II SAVANNAH and ORCHARD trials show that treatment with Tagrisso (osimertinib; AstraZeneca) produces significant survival benefits in patients with early-stage EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), with potential efficacy in combination therapies for advanced disease.1
These results, presented at the European Lung Cancer Congress (ELCC), solidified the role of Tagrisso as a foundational medication for this patient population.
"A critical goal in treating every patient with lung cancer is to not only extend a patient's life but also maintain quality of life while on treatment," said Myung-Ju Ahn, MD, PhD, professor, Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, in a press release "The continued overall survival (OS) trend seen here at ELCC in the unresectable Stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment."
The global, randomized, double-blind, placebo-controlled Phase III LAURA trial enrolled 216 patients with unresectable, Stage III EGFRm NSCLC whose disease had not progressed following definitive platinum-based chemoradiotherapy. Patients were treated with 80 mg of once-daily Tagrisso or placebo until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
Results showed a median OS of 58.8 months in the Tagrisso group compared to 54.1 months with placebo. Notably, 78% of patients in the placebo group switched to Tagrisso upon experiencing disease progression. AstraZeneca noted that the high crossover rate could dilute the observed survival difference, making it harder to detect a significant benefit of earlier Tagrisso use. The hazard ratio was 0.67 (95% CI, 0.40-1.14) with 31% maturity. The trial will continue assessing OS, and no new safety signals have been identified.
The ongoing global Phase II SAVANNAH trial enrolled 369 patients with EGFRm, locally advanced, or metastatic NSCLC with mesenchymal-epithelial transition overexpression and/or amplification whose disease progressed on first-line Tagrisso. Patients were randomly assigned to receive 300 mg or 600 mg once daily, or 300 mg twice daily of Orpathys (savolitinib) in combination with 80 mg of once-daily Tagrisso, or a combination of 300 mg twice daily Orpathys and placebo. The primary endpoint is overall response rate (ORR), with key secondary endpoints that included progression-free survival (PFS) and duration of response (DoR).
Early results showed that Tagrisso plus Orpathys achieved a 56% ORR, a median DoR of 7.1 months, and a median PFS of 7.4 months. The safety profile was consistent with previous studies, with grade 3 or higher adverse events (AEs) reported in 57% of patients.
The open-label, multi-center, Phase II ORCHARD trial evaluated 247 patients with advanced EGFRm NSCLC whose disease progressed on first-line Tagrisso. The study assessed 10 different Tagrisso-based combinations, with a primary endpoint of ORR and key secondary endpoints that included PFS and DoR.
Results from the Tagrisso plus Datroway (datopotamab deruxtecan) module showed an ORR of 43% in the 6 mg group and 36% in the 4 mg group. Median PFS was 11.7 months and 9.5 months, respectively. At nine months, 64% of patients in the 6 mg group remained responsive compared to 15% in the 4 mg group. Grade 3 or higher AEs occurred in 34% of patients on the 4 mg dose and 56% on the 6 mg dose. No new safety signals were identified.
The randomized, open-label, multi-center, global Phase III FLAURA2 trial evaluated 557 patients with locally advanced or metastatic EGFRm NSCLC. All patients received 80 mg of once-daily Tagrisso with chemotherapy (pemetrexed plus cisplatin or carboplatin) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial's primary endpoint was PFS.
Results showed a median PFS of two years, regardless of the duration of pemetrexed maintenance therapy. The safety profile of the Tagrisso-chemotherapy combination was consistent with known profiles of both medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received three to less than nine months of pemetrexed maintenance and 10% of patients who received over nine months. Chemotherapy discontinuation rates due to AEs were 18% for the three-to-nine-month group and 10% for the over nine-month group.1
"Having now treated more than one million patients around the world, Tagrisso has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment," said Susan Galbraith, EVP, oncology hematology R&D, AstraZeneca, in the press release. "The breadth of data at ELCC reinforce Tagrisso as the backbone therapy for patients with this disease and show that adding Orpathys or Datroway at the time of disease progression can help prolong patients' responses to treatment."
Reference
1. New study results reinforce Tagrisso as the backbone therapy for EGFR-mutated lung cancer across stages and settings. AstraZeneca. March 26, 2025. Accessed March 26, 2025. Https://www.Astrazeneca.Com/media-centre/press-releases/2025/new-study-results-reinforce-tagrisso-as-the-backbone-therapy-for-egfr-mutated-lung-cancer-across-stages-and-settings.Html
New Targeted Therapy Strategies For Addressing Non-Small Cell Lung Cancer Metastatic Disease
Targeted therapies have significantly improved outcomes for patients with non-small cell lung cancer (NSCLC) with actionable mutations. However, many tumors inevitably develop drug resistance and progress. (1) Metastatic disease develops in about 50% of patients with surgically resected early-stage NSCLC and is a driving factor for why it remains the leading cause of cancer-related deaths in the United States. (2) (3)
Thoracic medical oncologists and early drug development specialists at Memorial Sloan Kettering Cancer Center (MSK) continue to investigate new ways to improve outcomes for this patient population.
This article highlights three clinical trials of new treatment approaches for patients with epidermal growth factor receptor (EGFR)-mutated lung cancer metastases. It also shares key findings from preclinical research and evidence from three case studies from the ongoing phase 1/2 ALKOVE-1 clinical trial, the first study to evaluate a brain-penetrant anaplastic lymphoma kinase (ALK)-selective inhibitor for patients with heavily pretreated ALK fusion-positive NSCLC.
EGFR-Mutated Lung CancerEGFR pathway activation is found in 15% to 40% of NSCLC, and the incidence of brain metastases in patients with EGFR-mutant NSCLC is estimated to be up to 70%. (4)
MSK thoracic medical oncologist and early drug development specialist Helena A. Yu, MD, is leading three clinical trials evaluating new targeted therapies for EGFR-mutated metastatic NSCLC:
1. Amivantamab plus lazertinib improved responses in EGFR-mutated lung cancer with active brain metastases and leptomeningeal disease
Amivantamab is a bispecific antibody that targets EGFR and MET protein and also causes antibody-dependent cellular cytotoxicity. (5) Lazertinib is an oral third-generation selective inhibitor of EGFR. (6)
The MSK-exclusive study (NCT04965090) enrolled 20 adults with brain metastases and 21 with leptomeningeal disease. Patients received a median of two prior lines of therapy before treatment with amivantamab plus lazertinib.
For the brain metastases group, the systemic objective response rate (ORR) was 30%, and the intracranial ORR was 40%, with a median time on treatment of 3.9 months. In the leptomeningeal disease group, the systemic ORR was 32%, and the intracranial ORR was 23%, with a median time on treatment of 8.1 months. (7)
No serious side effects occurred, underscoring the importance of including patients with brain metastases and leptomeningeal disease in clinical trials testing EGFR-targeted therapies.
The study was funded by Janssen Oncology. Access disclosures for Dr. Yu.
2. Osimertinib alone or with chemotherapy for EGFR-mutated metastatic lung cancer
Osimertinib, an oral selective third-generation EGFR inhibitor, (8) is the usual treatment for EGFR-mutated NSCLC. This phase 2 study is evaluating whether adding carboplatin and pemetrexed to osimertinib can improve response rates and progression-free survival (PFS).
Only patients with persistent EGFR in circulating tumor DNA (ctDNA) after initiating therapy with osimertinib are randomized to either continuing osimertinib alone versus adding chemotherapy to osimertinib.
Dr. Yu is the principal investigator of the study (NCT04410796), which is open at 10 sites across the U.S. And seeks to enrol more than 570 patients. The aim of the study is to risk-stratify patients and match them to the appropriate therapy for their cancer.
3. Osimertinib alone or with bevacizumab as initial treatment for EGFR-mutated metastatic NSCLC
Dr. Yu is the lead principal investigator for the multisite phase 3 trial of osimertinib with or without the antiangiogenic agent bevacizumab. Sponsored by the National Cancer Institute, the study includes more than 590 U.S. Locations and seeks to enroll 300 participants (NCT04181060).
This clinical trial builds on earlier work by Dr. Yu and other MSK researchers that found intracranial response to osimertinib was excellent for patients with EGFR-mutant NSCLC with de novo, previously untreated brain metastases. (9)
The primary endpoint is PFS, and the secondary study objectives include overall survival (OS), ORR, duration of objective response, time to central nervous system (CNS) progression and CNS PFS, and toxicity. Recruiting continues at MSK and other locations. The estimated trial completion date is December 2026. Read more.
ALK-Fusion Positive Lung CancerALK fusions occur in up to 5% of patients diagnosed with NSCLC. (10) Six tyrosine kinase inhibitors (TKIs) spanning three generations have been approved for ALK fusion-positive NSCLC. As initial therapy, all of these agents produce ORRs from 70% to 80%, and each successive generation has improved CNS activity and median PFS.
However, effective treatment strategies following disease relapse remain limited. For example, the third-generation drug lorlatinib after a second-generation ALK TKI is associated with a broad range of CNS effects that occur in 52% of patients, including psychotic effects, dizziness, gait disturbances, and changes in mood, cognitive function, and mental status. These CNS effects are caused by the off-target inhibition of tropomyosin receptor kinase (TRK). (11)
Neladalkib shows promising activity in heavily pretreated ALK fusion-positive NSCLC
Preclinical and translational research by thoracic medical oncologist Alexander Drilon, MD, Chief of MSK's Early Drug Development Service, in collaboration with Nuvalent, has culminated in the first-in-human clinical trial of neladalkib (NVL-655), a novel, brain-penetrant ALK-selective inhibitor.
Neladalkib is a rationally designed TKI with a greater than 50 times selectivity for ALK over 96% of the kinome tested. It was created to provide activity against ALK single and compound mutations that have developed resistance to previous-generation ALK inhibitors, avoid inhibition of the TRK proteins, and address brain metastases. (12)
In a paper published in Cancer Discovery in December 2024, Dr. Drilon and colleagues reported their preclinical research findings and supporting evidence from three case studies from the ongoing international phase 1/2 ALKOVE-1 clinical trial. Highlights of their findings are as follows: (12)
The ALKOVE-1 study (NCT05384626) is currently recruiting patients at 70 institutions, including five cohorts of patients with locally advanced or metastatic NSCLC with an ALK rearrangement or activating ALK mutation and one cohort of patients with other solid tumors with ALK mutations. Dr. Drilon is the principal investigator for the study at MSK, which is enrolling patients at seven locations. Read more.
Based on early data, the U.S. Food and Drug Administration granted neladalkib breakthrough designation in May 2024 for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have been previously treated with two or more TKIs. (12)
The ALKOVE-1 study is sponsored by Nuvalent. Access disclosures for Dr. Drilon.
Read more about MSK's research into new treatment approaches for patients with lung cancer metastatic disease:
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