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Pfizer’s Lorbrena extends life for patients with rare lung cancer

Pfizer’s lung cancer drug Lorbrena can extend life for patients with a rare form of the disease for years longer than other drugs, according to new research published Friday.

The drug treats a type of non-small cell lung cancer with a genetic mutation called ALK. Non-small cell lung cancers account for about 85% of lung cancer diagnoses , and ALK-positive cancers account for about 4% of those diagnoses — more than 70,000 people every year.

The cancer tends to occur in younger patients who are nonsmokers .

It’s also particularly deadly: ALK-positive lung cancers are especially adept at spreading to the brain. About 25% of patients have brain metastasis within the first two years of being diagnosed.

“As time moves on, that increases,” said Dr. Ben Solomon, head of lung medical oncology at the Peter MacCallum Cancer Centre in Australia, who led the Pfizer-supported study.

The new research, a follow-up to a previous phase 3 clinical trial , found that after five years, 60% of patients who got Lorbrena were still alive, compared with 8% of patients who received a different drug, crizotinib (Xalkori, also from Pfizer).

The study was published in the Journal of Clinical Oncology and will be presented Friday at the American Society of Clinical Oncology’s annual meeting in Chicago.

“These results are remarkable,” said Dr. John Heymach, the chair of thoracic and head and neck medical oncology at the MD Anderson Cancer Center in Houston, who was not involved with the study. “For the first time, we are seeing that most patients go more than five years without their cancer progressing, and that is more than any other drug in the space. Previously, the best drugs we had were two to three years.”

There is one caveat: The drug that Lorbrena was compared to, crizotinib, is no longer used in the U.S., said Dr. Julie Gralow, the chief medical officer and executive vice president at the American Society of Clinical Oncology.

Both drugs — part of a class of medications called tyrosine kinase inhibitors — fight tumor cells in generally the same way. However, crizotinib is a first-generation version of this type of drug, whereas lorlatinib (the generic name for Lorbrena) is the third generation.

The current standard of care, meaning the drugs oncologists typically use to treat ALK-positive lung cancers , includes Lorbrena and two second-generation drugs: brigatinib (Takeda’s Alunbrig) and alectinib (Genentech’s Alecensa).

“In an ideal world, we would have compared lorlatinib to one of those, but the study was started before those were approved,” Gralow said. 

Still, “this is the best long-term data we’ve ever seen for” this class of drugs, she said. “This is just the most impressive progression-free survival we’ve ever seen in this population.”

The new study also found that the patients taking Lorbrena were nearly 95% less likely to have their cancer spread to their brain than those taking crizotinib. Four of the 114 patients taking Lorbrena developed brain metastasis within about 16 months, compared to 39 out of the 109 taking crizotinib, a huge feat for people living with ALK-positive lung cancer.

“Earlier drugs like crizotinib were not effective at blocking the spread in the brain,” Heymach said. While alectinib and brigatinib do have some ability to block tumors from spreading to the brain, he added, “the activity we’re seeing in the brain for lorlatinib is really unprecedented.”

The reason Lorbrena is so effective at preventing and treating brain metastasis is its ability to cross a membrane called the blood-brian barrier and enter the brain, something not all drugs can do.

“When the cancer spreads to the brain , that often leads to a marked decline in quality of life and really horrible side effects,” Heymach said.

Only a trial that compares all three standard-of-care drugs head to head, rather than to crizotinib can determine which is superior, said Dr. Isabel Preeshagul, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.

However, “it does seem that lorlatinib may have an edge in regards to CNS efficacy,” Preeshagul said, referring to the drug’s ability to treat and prevent spread to the brain. “This was a big unmet need for patients that harbor” the ALK mutation.

With its exceptional ability to cross into the brain comes the potential for more side effects, said Dr. Aaron Mansfield, a medical oncologist at the Mayo Clinic in Rochester, Minnesota.

People taking Lorbrena may be more prone to memory or mood issues compared to those taking similar second-generation drugs.

Solomon, the study leader, said because of this, the drug might not be the best choice for people with psychiatric disorders.

But a lower dose may be able to remedy the drugs’ neurotoxicity.

“We know that reducing the dose is very effective at reducing the cognitive side effects, and in those patients, outcomes were just as good as those that didn’t lower the dose,” Solomon said.

All four tyrosine kinase inhibitors only work in people who have ALK-positive lung cancer, not other types of lung cancer. While most mutations are caused by a single change in a gene, the ALK-positive mutation occurs when two genes break and then fuse together. Because of this, it’s sometimes referred to as ALK fusion.

Preeshagul said it’s important for patients diagnosed with lung cancer to advocate for themselves and ask for further testing to determine if they have the mutation, which is missed without additional tests.

“If you are diagnosed with stage 4 lung cancer, it’s important to ask your oncologist to send off next-generation sequencing,” she said. “If you have an ALK fusion, you should absolutely be on targeted therapy. The treatments that we have are life-altering.”

Kaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.

Berkeley Lovelace Jr. is a health and medical reporter for NBC News. He covers the Food and Drug Administration, with a special focus on Covid vaccines, prescription drug pricing and health care. He previously covered the biotech and pharmaceutical industry with CNBC.

Lung Cancer Research Results and Study Updates

See Advances in Lung Cancer Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

FDA has approved alectinib (Alecensa) as adjuvant therapy for people with lung cancer who have ALK-positive tumors. In a clinical trial, alectinib helped people live longer after surgery without their cancer returning than chemotherapy.

The results of the clinical trial that led to FDA’s 2023 approval of repotrectinib (Augtyro) for lung cancers with ROS1 fusions have been published. The drug shrank tumors in 80% of people receiving the drug as an initial treatment.

A collection of material about the ALCHEMIST lung cancer trials that will examine tumor tissue from patients with certain types of early-stage, completely resected non-small cell lung cancer for gene mutations in the EGFR and ALK genes, and assign patients with these gene mutations to treatment trials testing post-surgical use of drugs targeted against these mutations.

Tarlatamab, a new type of targeted immunotherapy, shrank small cell lung cancer (SCLC) tumors in more than 30% of participants in an early-stage clinical trial. Participants had SCLC that had progressed after previous treatments with other drugs.

For people with lung cancer and medullary thyroid cancer whose tumors have changes in the RET gene, selpercatinib improved progression-free survival compared with other common treatments, according to new clinical trial results.

In the ADAURA clinical trial, people with early-stage lung cancer treated with osimertinib (Tagrisso) after surgery lived longer than people treated with a placebo after surgery. Despite some criticisms about its design, the trial is expected to change patient care.

For certain people with early-stage non-small cell lung cancer, sublobar surgery to remove only a piece of the affected lung lobe is as effective as surgery to remove the whole lobe, new research shows.

Pragmatica-Lung is a clinical trial for people with non-small cell lung cancer that has spread beyond the lungs (stage 4 cancer). The trial will help confirm if the combination of pembrolizumab and ramucirumab helps people with advanced lung cancer live longer.

On August 11, the Food and Drug Administration (FDA) gave accelerated approval to trastuzumab deruxtecan (Enhertu) for adults with non-small cell lung cancer (NSCLC) that has a specific mutation in the HER2 gene. Around 3% of people with NSCLC have this kind of HER2 mutation.

Giving people with early-stage lung cancer the immunotherapy drug nivolumab (Opdivo) and chemotherapy before surgery can substantially delay the progression or return of their cancer, a large clinical trial found.

Atezolizumab (Tecentriq) is now the first immunotherapy approved by FDA for use as an additional, or adjuvant, treatment for some patients with non-small cell lung cancer. The approval was based on results of a clinical trial called IMpower010.

Quitting smoking after a diagnosis of early-stage lung cancer may help people live longer, a new study finds. The study, which included more than 500 patients, also found that quitting smoking delayed the cancer from returning or getting worse.

NCI scientists and their international collaborators have found that the majority of lung cancers in never smokers arise when mutations caused by natural processes in the body accumulate. They also identified three subtypes of lung cancer these individuals.

FDA has approved the first KRAS-blocking drug, sotorasib (Lumakras). The approval, which covers the use of sotorasib to treat some patients with advanced lung cancer, sets the stage for other KRAS inhibitors already in development, researchers said.

Combining the chemotherapy drug topotecan and the investigational drug berzosertib shrank tumors in some patients with small cell lung cancer, results from an NCI-supported phase 1 clinical trial show. Two phase 2 trials of the combination are planned.

Mortality rates from the most common lung cancer, non-small cell lung cancer (NSCLC), have fallen sharply in the United States in recent years, due primarily to recent advances in treatment, an NCI study shows.

In a study of more than 50,000 veterans with lung cancer, those with mental illness who received mental health treatment—including for substance use—lived substantially longer than those who didn’t participate in such programs.

FDA has granted accelerated approval for selpercatinib (Retevmo) to treat certain patients with thyroid cancer or non-small cell lung cancer whose tumors have RET gene alterations. The drug, which works by blocking the activity of RET proteins, was approved based on the results of the LIBRETTO-001 trial.

Osimertinib (Tagrisso) improves survival in people with non-small cell lung cancer with EGFR mutations, updated clinical trial results show. People treated with osimertinib lived longer than those treated with earlier-generation EGFR-targeted drugs.

A large clinical trial showed that adding the immunotherapy drug durvalumab (Imfinzi) to standard chemotherapy can prolong survival in some people with previously untreated advanced small cell lung cancer.

The investigational drug selpercatinib may benefit patients with lung cancer whose tumors have alterations in the RET gene, including fusions with other genes, according to results from a small clinical trial.

FDA has approved entrectinib (Rozlytrek) for the treatment of children and adults with tumors bearing an NTRK gene fusion. The approval also covers adults with non-small cell lung cancer harboring a ROS1 gene fusion.

Clinical recommendations on who should be screened for lung cancer may need to be reviewed when it comes to African Americans who smoke, findings from a new study suggest.

Use of a multipronged approach within hospitals, including community centers, not only eliminated treatment disparities among black and white patients with early-stage lung cancer, it also improved treatment rates for all patients, results from a new study show.

In everyday medical care, there may be more complications from invasive diagnostic procedures performed after lung cancer screening than has been reported in large studies.

The Lung Cancer Master Protocol, or Lung-MAP, is a precision medicine research study for people with advanced non-small cell lung cancer that has continued to grow after treatment. Patients are assigned to different study drug combinations based on the results of genomic profiling of their tumors.

On December 6, 2018, the Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with a standard three-drug regimen as an initial treatment for advanced lung cancer that does not have EGFR or ALK mutations.

A new study has identified a potential biomarker of early-stage non–small cell lung cancer (NSCLC). The biomarker, the study’s leaders said, could help diagnose precancerous lung growths and early-stage lung cancers noninvasively and distinguish them from noncancerous growths.

Results from two large clinical trials should cement the value of the drugs brigatinib (Alunbrig) and durvalumab (Imfinzi) in treating non-small cell lung cancer (NSCLC). The trial results, several experts said, confirm that the drugs can improve the outcomes of patients with advanced NSCLC.

Cancer researchers have trained a computer program to scan images of tissue samples to differentiate normal lung tissue from the two most common forms of lung cancer. The program also learned to detect cancer-related genetic mutations in the samples.

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Top advances in lung cancer, 2021

Nisha a. mohindra.

1 Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

2 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA

Jyoti D. Patel

Despite a global pandemic that continued to inflict chaos and confusion on the world, resulting in fewer cancer screenings and delayed surgeries, remarkable lung cancer treatment advancements were made in 2021. From immunotherapy in the adjuvant setting to the approval of the first-in-class, highly selective inhibitor of KRAS G12C, these treatment advances have significant clinical impact in patients with lung cancer.

INTRODUCTION

The treatment paradigm and outcomes for patients with lung cancer have vastly evolved over the last several decades, largely because the use of immune checkpoint inhibitors and targeted therapies. 1 This past year, we continued to see immense progress for nonsmall cell lung cancer (NSCLC) as immunotherapy entered earlier stages of disease and innovative strategies were developed to effectively target some of our more difficult-to-treat subsets of disease.

IMMUNOTHERAPY IN THE ADJUVANT SETTING

In October 2021, the US Food and Drug Administration approved atezolizumab for adjuvant treatment after resection and platinum-based chemotherapy in patients with stage II–IIIA NSCLC whose tumors have PD-L1 expression on ≥1% of tumor cells. 2 In the IMpower010 trial ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02486718","term_id":"NCT02486718"}} NCT02486718 ), a randomized, multinational, phase 3 trial, adjuvant atezolizumab was compared with best supportive care in patients with completely resected, stage IB–IIIA NSCLC (according to the American Joint Committee on Cancer AJCC Cancer Staging Manual , seventh edition) after adjuvant platinum-based chemotherapy. 3 In total, 1005 patients were randomized in a 1:1 fashion to receive either atezolizumab for a 1-year duration ( n = 507) or best supportive care ( n = 498). All patients received adjuvant platinum-based chemotherapy before atezolizumab. After a median follow-up of 32 months, adjuvant atezolizumab demonstrated a significant improvement in disease-free survival (DFS) in the stage II–IIIA PD-L1 ≥ 1% population with a hazard ratio (HR) of 0.66 (95% CI, 0.50–0.88; p = .0039) and a 3-year DFS rate of 60% compared with 48% in the best supportive care group. In the overall stage II–IIIA population, a DFS benefit was noted, with an HR of 0.79 (95% CI, 0.64–0.96; p = .020); however, in the intention-to-treat population, which included stage IB–IIIA disease, the boundary for statistical significance for DFS was not crossed (HR, 0.81; 95% CI, 0.67–0.99; p = .040). The magnitude of benefit was most striking in patients who had PD-L1 expression on ≥50% of tumor cells (HR, 0.43; 95% CI, 0.27–0.68). Treatment with adjuvant atezolizumab did not yield any new safety concerns. Although overall survival results from this trial are still immature, we now have options for effective adjuvant therapy with both osimeritinib in resected epidermal growth factor receptor ( EGFR ) mutation–positive disease and atezolizumab in resected stage II and III PD-L1–positive NSCLC. 4

Beyond the adjuvant setting, there remains much interest in the potential of immunotherapy in the neoadjuvant setting. In the preoperative setting, intact tumor and tumor antigens may yield higher T-cell responses from immunotherapy. The CheckMate 816 trial ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02998528","term_id":"NCT02998528"}} NCT02998528 ) was the first phase 3 trial in NSCLC to report a significant improvement in rates of pathologic complete response with neoadjuvant nivolumab and chemotherapy versus chemotherapy alone (24.0% vs. 2.2%; p < .0001). 5 Patients on the trial were randomized to receive either three cycles of nivolumab and platinum-doublet chemotherapy or three cycles of chemotherapy, followed by surgery. Eighty-three percent of patients on nivolumab/chemotherapy and 75% of patients who received chemotherapy underwent definitive resection, suggesting that the addition of neoadjuvant immunotherapy did not affect the extent or timing of surgical resection. 6 Further data from this trial and others like it are awaited as we see the potential impact of these agents on survival, gain clarity about the impact of a pathologic complete response on lung cancer survival, and learn how to best integrate immunotherapy with surgery.

NOVEL AGENTS

Despite great advancements in targeted therapies for NSCLC, there remain molecular subsets in which effective targeted agents have remained elusive. In 2021, we saw three of these difficult-to-drug subsets, Kirsten rat sarcoma (KRAS ), EGFR exon 20, and human epidermal growth factor receptor 2 ( HER2 ) mutations, achieve meaningful outcomes with novel agents.

Activating mutations in the KRAS oncogene are found in 25%–30% of lung adenocarcinomas; however, there are distinct molecular underpinnings that make this group of mutations difficult to target and lead to various clinical and therapeutic outcomes. 7 , 8 In May 2021, a novel drug, sotorasib, was approved to treat the most frequent variant among KRAS mutations, KRAS p.G12C, which comprises 13% of lung adenocarcinomas. 8 , 9 Sotorasib is a small molecule that irreversibly binds to a pocket of the switch II region of KRAS p.G12C that is only present when KRAS p.G12C is in its inactive conformation. 10 , 11 Therefore, when sotorasib is bound, KRAS p.G12C is blocked from cycling from an inactive state to an activated state.

The CODEBREAK trial ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT04185883","term_id":"NCT04185883"}} NCT04185883 ) was a single-arm, phase 2 trial evaluating the efficacy of sotorasib in patients with KRAS p.G12C–mutant NSCLC that had progressed on prior lines of therapy. 12 Of the 124 evaluable patients treated with sotorasib, 37% had an objective response (95% CI, 28.6%–46.2%), and 81% of patients achieved disease control (95% CI, 72.6%–87.2%).The median progression-free survival (PFS) was 6.8 months (95% CI, 5.1–8.2 months), the median duration of response (DOR) was 11.1 months (95% CI, from 6.9 months to not evaluable), and the median overall survival was 12.5 months (95% CI, from 10.0 months to not evaluable). Treatment-related adverse events (AEs) occurred in 70% of patients, and the most common were diarrhea (32%), fatigue (11%), and emesis (8%). Sotorasib demonstrated durable clinical benefit in the majority of patients on trial and had promising efficacy in some of our most difficult-to-treat subsets of disease. Other novel agents, such as adagrasib, have also demonstrated promising activity in KRAS p.G12C–mutant NSCLC and may become additional agents available to this disease subset in the future. 13

Another subset of NSCLC that has lacked effective targeted therapies is NSCLC with EGFR exon 20 gene insertion mutations, which includes 2% of lung adenocarcinomas. 14 , 15 Exon 20 insertions result in a restricted drug-binding pocket within the EGFR tyrosine kinase domain, making conventional EGFR tyrosine kinase inhibitors largely ineffective. 14 , 16 Prior efforts to develop effective targeted treatments have yielded low response rates (range, 5%–20%) and various degrees of toxicity. 17 – 19 In late 2021, two agents for EGFR exon 20 insertion mutations were approved: amivantamab, a bispecific antibody directed at EGFR and MET, and mobocertinib, an oral tyrosine kinase inhibitor developed to select for EGFR exon 20 insertion mutations.

Amivantinib, a fully human, bispecific antibody, binds to both EGFR and MET extracellular domains, leading to inhibition of ligand binding, endocytosis, and degradation of the receptor–antibody complex, as well as destruction by macrophages and antibody-dependent cellular cytotoxicity by natural killer cells. 20 , 21 In the CHRYSALIS study ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02609776","term_id":"NCT02609776"}} NCT02609776 ), a first-in-human, phase 1, dose-escalation and dose-expansion study, amivantinib demonstrated a 40% overall response rate among 81 evaluable patients, with a median DOR of 11.1 months (95% CI, from 6.9 months to not evaluable). 22 The most common AEs were rash (86%), infusion-related reaction (66%), paronychia (45%), and constipation (24%).

Mobocertinib is a novel, potent, irreversible EGFR tyrosine kinase inhibitor designed specifically to inhibit activating EGFR exon 20 insertion mutations with relative sparing of wild-type EGFR. 23 The Study 101 trial ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02716116","term_id":"NCT02716116"}} NCT02716116 ) was a multicohort, nonrandomized, open-label trial evaluating the efficacy of mobocertinib in patients who had locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. In the 114 patients whose disease had progressed on or after platinum-based chemotherapy, mobocertinib produced an overall response rate of 28% (95% CI, 20%–37%), with a median DOR of 17.5 months (95% CI, 7.4–20.3 months). The median PFS was 7.3 months (95% CI, 5.5–9.2 months), and the median OS was 24.0 months (95% CI, 14.6–28.8 months). The most common AEs were diarrhea (91%) and rash (45%).

Patients with HER2 gene mutations, which are identified in 3% of NSCLC adenocarcinomas, represent another population that has lacked effective targeted agents because previous HER2–directed therapies have only resulted in limited efficacy in NSCLC. 4 , 24 – 27 Trastuzumab deruxtecan is an antibody–drug conjugate of humanized anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload that leads to cellular apoptosis when the payload is intracellularly released. 28 DESTINY-Lung01 ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03505710","term_id":"NCT03505710"}} NCT03505710 ) was a single-arm, phase 2 trial that evaluated the efficacy of trastuzumab deruxtecan among 91 pretreated patients with metastatic, HER2 -mutant NSCLC. 29 After 13.1 months of follow-up, 55% of patients had a confirmed overall response (95% CI, 44%–65%), and 92% achieved disease control. The median PFS was 8.2 months (95% CI, 6.0–11.9 months), and the median OS was 17.8 months (95% CI, 13.8–22.1 months). Nearly all patients had at least one AE, and the most common AEs were nausea (73%), fatigue (53%), and anemia (35%). Interstitial lung disease (ILD) occurred in 26% of patients; 7% of patients had grade ≥ 3 ILD, and two patients died from ILD. Trastuzumab deruxtecan is an effective targeted therapy option for patients with metastatic, HER2 -mutant NSCLC and has achieved US Food and Drug Administration breakthrough designation. Despite this efficacy, ongoing research will be needed to understand and mitigate the risk of treatment-related ILD in patients with NSCLC.

The demonstrated efficacy of four different agents to target three different subsets of NSCLC underscores the importance of molecular testing and PD-L1 testing in NSCLC. Current guidelines now recommend testing for numerous biomarkers at the time of diagnosis in advanced stage NSCLC— EGFR , ALK , ROS1 , BRAF , KRAS , NTRK , MET , RET , and HER2 —highlighting the wide breadth of targets and corresponding therapies that can be leveraged for disease management. In early stage disease, testing tumors for EGFR mutations and PD-L1 has become paramount given the advances made in adjuvant treatments. As we look back at the last year, it truly was one marked by innovation and the integration of effective therapies for patients with lung cancer. In particular, the addition of immunotherapy as adjuvant therapy in early stage disease and the ability to develop targeted therapies (bispecific antibodies, antibody–drug conjugates, and small-molecule inhibitors) for new subsets of patients are notable advances that will further improve outcomes for patients with NSCLC.

Lay summary

• There has been tremendous innovation in the treatment of nonsmall cell lung cancer.
• The year 2021 was marked by new approaches to adjuvant therapy and the availability of agents to target new subsets of nonsmall cell lung cancer.

Funding information

Nisha A. Mohindra is supported by grant AHRQ-K12HS02638 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. Jyoti D. Patel is supported by a Cancer Center Core Grant from the National Cancer Institute, National Institutes of Health (3P30CA060553-26S2).

CONFLICTS OF INTEREST

Nisha A. Mohindra reports grants from Pfizer Inc. and personal fees from Astra Zeneca outside the submitted work. Jyoti D. Patel reports grants from Bristol-Myers Squibb and personal fees from AbbVie, AstraZeneca, Eli Lilly & Company, Genentech USA, Inc., and Takeda Oncology outside the submitted work.

Trial registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02486718","term_id":"NCT02486718"}} NCT02486718 .

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Recent advances in lung cancer research: unravelling the future of treatment

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• Published: 06 April 2024

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• Luca Bertolaccini   ORCID: orcid.org/0000-0002-1153-3334 1 ,
• Monica Casiraghi 1 , 2 ,
• Clarissa Uslenghi 1 ,
• Sebastiano Maiorca 1 &
• Lorenzo Spaggiari 1 , 2  

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Lung cancer, a multifaceted disease, demands tailored therapeutic approaches due to its diverse subtypes and stages. This comprehensive review explores the intricate landscape of lung cancer research, delving into recent breakthroughs and their implications for diagnosis, therapy, and prevention. Genomic profiling and biomarker identification have ushered in the era of personalised medicine, enabling targeted therapies that minimise harm to healthy tissues while effectively combating cancer cells. The relationship between pulmonary tuberculosis and lung cancer is examined, shedding light on potential mechanisms linking these two conditions. Early detection methods, notably low-dose computed tomography scans, have significantly improved patient outcomes, emphasising the importance of timely interventions. There has been a growing interest in segmentectomy as a surgical intervention for early-stage lung cancer in recent years. Immunotherapy has emerged as a transformative approach, harnessing the body's immune system to recognise and eliminate cancer cells. Combining immunotherapy with traditional treatments, such as chemotherapy and targeted therapies, has shown enhanced efficacy, addressing the disease's heterogeneity and overcoming drug resistance. Precision medicine, guided by genomic profiling, has enabled the development of targeted therapies like tyrosine kinase inhibitors, offering personalised treatments tailored to individual patients. Challenges such as drug resistance and limited accessibility to advanced therapies persist, emphasising the need for collaborative efforts and innovative technologies like artificial intelligence. Despite challenges, ongoing interdisciplinary collaborations and technological advancements offer hope for a future where lung cancer is treatable and preventable, reducing the burden on patients and healthcare systems worldwide.

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This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds.

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Bertolaccini, L., Casiraghi, M., Uslenghi, C. et al. Recent advances in lung cancer research: unravelling the future of treatment. Updates Surg (2024). https://doi.org/10.1007/s13304-024-01841-3

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After 40 years of smoking, she survived lung cancer thanks to new treatments

Yuki Noguchi

Denise Lee on her last day of chemo. In addition to chemo and surgery, she was treated with immunotherapy. She's currently in remission. Denise Lee hide caption

Denise Lee on her last day of chemo. In addition to chemo and surgery, she was treated with immunotherapy. She's currently in remission.

Denise Lee grew up in Detroit in the mid-1970s and went to an all-girls Catholic high school. She smoked her first cigarette at age 14 at school, where cigarettes were a popular way of trying to lose weight.

Instead, her nicotine addiction lasted four decades until she quit in her mid-50s.

"At some point it got up as high as 2.5 packs a day," Lee, 62, recalls.

Yet she didn't think about lung cancer risk — until she saw a billboard urging former smokers to get screened. Lee, a retired lawyer living in Fremont, Calif., used to drive past it on her way to work.

"The thing that caught my attention was the fact that it was an African American female on the front," she recalls.

Shots - Health News

The american cancer society says more people should get screened for lung cancer.

She eventually got the low-dose CT scan recommended for current and former smokers. When doctors found an early, but dangerous, tumor, Lee cried and panicked. Her mother had cared for her father, who'd died of prostate cancer. "My biggest concern was telling my mom," she says.

But that was six years ago, and Lee is cancer free today. Surgery removed the 2-inch tumor in her lung, then new treatments also boosted her immune system, fighting off any recurrence.

Lung cancer remains the most lethal form of the disease, killing about 135,000 Americans a year – more than breast, prostate and colon cancer combined – which is why many people still think of a diagnosis as synonymous with a death sentence. But with new treatments and technology, the survival rates from lung cancer are dramatically improving, allowing some patients with relatively late-stage cancers to live for years longer.

"If you're gonna have lung cancer, now is a good time," Lee says of the advances that saved her.

Denise Lee has been cancer-free for six years. She says she's grateful she got screened and caught her lung cancer early enough that treatment has been effective. Denise Lee hide caption

Denise Lee has been cancer-free for six years. She says she's grateful she got screened and caught her lung cancer early enough that treatment has been effective.

The key breakthrough, says Robert Winn, a lung cancer specialist at Virginia Commonwealth University, is the ability to better pinpoint the mutations of a patient's particular form of cancer. In the past, treatments were blunt tools that caused lots of collateral damage to healthy parts of the body while treating cancer.

"We've gone from that to molecular characterization of your lung cancer, and it has been a game changer," Winn says. "This is where science and innovation has an impact."

One of those game-changing treatments is called targeted therapy . Scientists identify genetic biomarkers in the mutated cancer cells to target and then deliver drugs that attack those targets, shrinking tumors.

CRISPR gene-editing may boost cancer immunotherapy, new study finds

Another is immunotherapy, usually taken as a pill, which stimulates the body's own defense system to identify foreign cells, then uses the immune system's own power to fight the cancer as if it were a virus.

As scientists identify new cancer genes, they're creating an ever-broader array of these drugs.

Combined, these treatments have helped increase national survival rates by 22% in the past five years – a rapid improvement over a relatively short time, despite the fact that screening rates are very slow to increase. Winn says as these treatments get cheaper and readily available, the benefits are even reaching rural and Black populations with historic challenges accessing health care.

The most remarkable thing about the drugs is their ability to, in some cases, reverse late-stage cancers. Chi-Fu Jeffrey Yang, a thoracic surgeon at Massachusetts General Hospital and faculty at Harvard Medical School, recalls seeing scans where large dark shadows of tumor would disappear: "It was remarkable to see the lung cancer completely melting away."

To Yang, such progress feels personal. He lost his beloved grandfather to the disease when Yang was in college. If he were diagnosed today, he might still be alive.

"Helping to take care of him was a big reason why I wanted to be a doctor," Yang says.

But the work of combating lung cancer is far from over; further progress in lung cancer survival hinges largely on getting more people screened.

Low-dose CT scans are recommended annually for those over 50 who smoked the equivalent of a pack a day for 20 years. But nationally, only 4.5% of those eligible get those scans , compared to rates of more than 75% for mammograms.

Andrea McKee, a radiation oncologist and spokesperson for the American Lung Association, says part of the problem is that lung cancer is associated with the stigma of smoking. Patients often blame themselves for the disease, saying: "'I know I did this to myself. And so I don't I don't think I deserve to get screened.'"

McKee says that's a challenge unique to lung cancer. "And it just boggles my mind when I hear that, because, of course, nobody deserves to die of lung cancer."

Denise Lee acknowledges that fear. "I was afraid of what they would find," she admits. But she urges friends and family to get yearly scans, anyway.

"I'm just so grateful that my diagnosis was early because then I had options," she says. "I could have surgery, I could have chemotherapy, I could be a part of a clinical trial."

And all of that saved her life.

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Trial reveals benefits of 'stepped' palliative care for patients with advanced lung cancer

by Massachusetts General Hospital

A new study led by investigators from Mass General Cancer Center reveals the effectiveness of more scalable ways of delivering palliative care to patients with advanced lung cancer.

The findings were highlighted at the American Society of Clinical Oncology's annual meeting and are published in JAMA in a paper titled "Stepped Palliative Care for Patients with Advanced Lung Cancer: A Multi-site Randomized Clinical Trial."

The study, led by Jennifer S. Temel, MD of the Mass General Cancer Center, assessed the effectiveness of stepped palliative care , in which all patients receive palliative care for their condition, but with a minimum of required contact with a specialty-trained clinician. More intensive treatment is reserved for those who do not benefit sufficiently from the less intensive care.

This randomized trial included 507 patients with advanced lung cancer who received either early standard palliative care or stepped palliative care.

Studies show that early palliative care, integrated with oncology care from the time of diagnosis of advanced cancer, improves patient and caregiver outcomes. However, this care model has not been widely implemented for two main reasons: the shortage of palliative care clinicians nationwide and challenges in providing palliative care visits throughout the course of cancer treatment, especially as novel therapeutics prolong survival.

Investigators in this study found that stepped palliative care, with visits occurring only at key points in patients' cancer trajectories and using a decrease in quality of life to trigger more visits, resulted in fewer palliative care visits without diminishing the benefits for patients' quality of life.

"To our knowledge, this is the first randomized trial to establish the non-inferiority of a palliative care strategy that's tailored to a patient's needs by triggering more intensive palliative care services based on patient-reported quality of life , compared with resource-intensive early palliative care," said Temel, who co-directs the Cancer Outcomes Research and Education Program and is the clinical director of Thoracic Oncology at Massachusetts General Hospital.

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Lung Cancer Was a Death Sentence. Now Drugs Are Saving Lives.

There is more hope than ever for people diagnosed with the deadliest cancer.

Declines in smoking and the advent of screening and newer drugs have transformed the outlook for patients with lung cancer, once considered a death sentence. Progress against the disease has propelled the drop in overall cancer deaths in the U.S. over the past three decades.

And there is more to gain. More patients can fend off the disease for months or years with targeted or immune-boosting drugs, results released this weekend at a top cancer conference showed. That includes patients with forms of the disease that are notoriously tough to treat.

“It had such an abysmal prognosis. And now we have people who are being cured who we never thought would be cured,” said Dr. Angela DeMichele, a medical oncologist at Penn Medicine.

AstraZeneca’s drug Tagrisso can contain lung cancer nearly three years longer than chemotherapy and radiation alone for some stage-three patients, one study released Sunday showed. Another found that some patients with aggressive disease survived nearly two years longer with the company’s immunotherapy drug Imfinzi, the first advance for that lung-cancer subtype in decades.

Another study presented at the American Society of Clinical Oncology conference in Chicago found that 60% of advanced patients were alive without their disease advancing at five years after taking Pfizer’s Lorbrena, a drug that targeted a genetic mutation in their tumors. That compares with just 8% of patients on an older drug with the same target.

“These results are really outstanding,” said Dr. David Spigel, chief scientific officer at Sarah Cannon Research Institute in Tennessee, lead researcher on the Imfinzi trial. “A really major step forward in lung-cancer care.”

Tagrisso, Imfinzi and Lorbrena are all approved by the Food and Drug Administration and in use.

Lorbrena has kept Matt Hiznay’s stage-four lung cancer at bay for nine years. Hiznay, who never smoked, was diagnosed in 2011 after a persistent cough at 24 years old.

“Hearing that, you get old really fast,” he said.

But there was some good news: His tumor tested positive for something called an ALK gene mutation, a rare finding that made him eligible for a targeted drug. Hiznay’s doctor shook his hand and congratulated him on being a mutant.

Hiznay tried a string of drugs and older therapies including chemotherapy and radiation, each of which held off his disease for some time. He joined a clinical trial for Lorbrena in 2015 and has taken the drug ever since. Between treatment, Hiznay earned a doctorate, got married and had a daughter.

“It became a bit easier to see the future again,” said Hiznay, who lives in Brecksville, Ohio. He cherishes each day, even when his infant daughter wakes him up in the middle of the night.

More than 234,000 Americans are diagnosed with lung cancer annually. It is the leading cause of cancer death among men and women, killing some 125,000 Americans each year. The lung-cancer survival rate has increased by some 20% in the past five years, according to the American Lung Association.

Lung cancer has responded to newer drugs such as immunotherapies better than some other cancers, doctors said, in part because its tumors tend to have many mutations that make it easier to find and attack.

Tagrisso targets mutations on the EGFR gene, found in 15% of lung cancers in the U.S. One study presented at the conference added Tagrisso after chemotherapy and radiation for patients with the mutation whose stage-three disease was too far along for surgery. The median time before the disease advanced in those patients was more than three years, compared with just under six months for patients who weren’t on the drug.

Patients in the study were intended to take Tagrisso indefinitely, rather than the three years that many patients take the drug after surgery. A future step would be to study the costs of longer-term treatment and whether some patients could stop it eventually, said Dr. Lecia Sequist, a lung-cancer specialist at Mass General Cancer Center who wasn’t involved in the trial.

The results show how much lung-cancer treatment has changed in the past decade, she said: “It’s like Dorothy looking around and saying we’re not in Kansas anymore.”

Another study showed rare progress against small-cell lung cancer, a less common and more aggressive form of the disease that is harder to treat. AstraZeneca’s Imfinzi increased median survival to around 56 months, compared with 33 months on the standard chemotherapy and radiation alone. The trial included patients with small-cell lung cancer that hadn’t spread.

“To see something where we’re measuring benefit in years versus months is a huge step in the right direction,” said Dr. Lauren Averett Byers, a lung-cancer oncologist at MD Anderson Cancer Center in Houston, who wasn’t involved in the trial.

The FDA in May approved Amgen’s Imdelltra for more advanced small-cell lung cancer. Median survival with the drug was 14 months, with 40% of patients responding to the treatment.

About a quarter of lung-cancer patients are alive five years after diagnosis. The newer treatments can give some patients with advanced disease months or years more to live, but the cancer often comes back and becomes incurable. Many lung cancers are caught late.

“When you look at the disease statistics, you have to be humbled a little bit,” said Dr. Pasi Jänne, a lung-cancer specialist at Dana-Farber Cancer Institute in Boston. “We still have room to go.”

Through Hiznay’s 13 years with lung cancer, he has seen many fellow patients die. “The survivor’s guilt, it’s there, it’s real,” he said.

Five years after his diagnosis, Hiznay rented a brewery basement for a “One Percent” party, celebrating his victory against the odds of survival in 2011. He did it again after 10 years. He plans to be there for 15.

Write to Brianna Abbott at [email protected]

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Thousands of NHS patients to access trials of personalised cancer ‘vaccines’

31 May 2024

Today, the NHS announced it has treated its first patient in England with a personalised vaccine against their bowel cancer, in a clinical trial part of NHS England’s new Cancer Vaccine Launch Pad .  

As part of the platform, which is run by our Southampton Clinical Trials Unit , thousands of cancer patients in England are set to gain fast-tracked access to trials of personalised cancer vaccines following the launch of a world-leading NHS trial ‘matchmaking’ service to help find new life-saving treatments.  

The vaccines being tested as part of the trials aim to help patients with different types of cancer and, if successfully developed, researched and approved, cancer vaccines could become part of standard care.  

“It’s incredibly exciting that patients in England are beginning to access personalised cancer vaccines for bowel cancer,” said Iain Foulkes, executive director of research and innovation at Cancer Research UK.  

“This technology pioneers the use of mRNA-based vaccines to sensitise people’s immune system and in turn detect and target cancer at its earliest stages.   

“Clinical trials like this are vital in helping more people live longer, better lives, free from the fear of cancer. If successful, the vaccine will be a game changer in preventing the onset or return of bowel cancer.”  

A UK first trial

Elliot Pfebve, 55, received the developmental jab at University Hospitals Birmingham NHS Foundation Trust, one of several sites taking part in the colorectal cancer vaccine trial sponsored by BioNTech SE.  

A higher-education lecturer, Elliot had no cancer symptoms and was diagnosed through a routine health check with his GP.   

Following blood tests, he was immediately invited to Manor Hospital in Walsall and triaged to a hospital ward to receive blood transfusions.  

A CT scan and a colonoscopy confirmed he had colon cancer and Eliott had surgery to remove the tumour and 30 cm of his large intestine.  

He was then referred to the Queen Elizabeth Hospital Birmingham for initial rounds of chemotherapy and to take part in a clinical trial.  

“Taking part in this trial tallies with my profession as a lecturer, and as a community-centred person,” he said.  

“I want to impact other people’s lives positively and help them realise their potential.   

“Through the potential of this trial, if it is successful, it may help thousands, if not millions of people, so they can have hope, and may not experience all I have gone through. I hope this will help other people.”  

How do cancer vaccines work?

The vaccine trial Elliot’s taking part in is one of several that will be taking place across the country to treat different types of cancer.  

Patients who agree to take part have a sample of their cancer tissue and a blood test taken.  

If they meet a clinical trial’s eligibility criteria, they can be referred to their nearest participating NHS site, meaning patients from hospitals across the country will find it easier than ever to take part in groundbreaking research.   

The investigational cancer vaccines evaluated in the colorectal cancer trial are based on a molecule called mRNA, the same technology used for the COVID-19 vaccine .  

They’re created by analysing a patient’s tumour to identify mutations specific to their own cancer. Using this information, medics can create an individualised cancer vaccine.  

The developmental vaccines are designed to induce an immune response that may prevent cancer from returning after surgery by stimulating the patient’s immune system to specifically recognise and potentially destroy any remaining cancer cells.  

The investigational cancer vaccines, which are being jointly developed by biopharmaceutical companies BioNTech and Genentech, are still undergoing trials and have not yet been approved by regulators.  

If successful, the vaccine will be a game changer in preventing the onset or return of bowel cancer.

The launch pad

19 hospitals in England are already signed up to the Cancer Vaccine Launch Pad, one of the biggest projects of its kind in the world, with more sites joining the platform over the coming months.    

Some trials have already enlisted patients, although the majority of participants are expected to be enrolled from 2026 onwards.  

The scheme aims to expand and work with a range of partners in the pharmaceutical industry to include patients across many cancer types who could potentially join a vaccine trial, such as those with pancreatic and lung cancer.   

“Seeing Elliot receive his first treatment as part of the Cancer Vaccine Launch Pad is a landmark moment for patients and the health service as we seek to develop better and more effective ways to stop this disease,” said Amanda Pritchard, NHS chief executive.  

“Thanks to advances in care and treatment, cancer survival is at an all-time high in this country, but these vaccine trials could one day offer us a way of vaccinating people against their own cancer to help save more lives.   

“The NHS is in a unique position to deliver this kind of world-leading research at size and scale, and as more of these trials get up and running at hospitals across the country, our national match-making service will ensure as many eligible patients as possible get the opportunity to access them.”  

The NHS is working in partnership with Genomics England on the launch pad, with work already helping patients access the latest testing technologies and ensures they are given more targeted precision treatments for their cancer.  

This would be amazing. I have ALk Positive lung cancer diagnosed at 52 and having never ever smoked. When the targeted therapy stops working if I have access to these trails that would be incredible

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