An encouraging – and exciting – slew of results and progress in the quest to bolster the arsenal against cancer were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago before tens of thousands of oncologists, health researchers and scientists this weekend.
This included an extraordinary treatment which suggests the halting of the progress of lung cancer, another which almost cuts in half the progression of deadly multiple myeloma, an “unprecedented” drug in slowing breast cancer’s march; an “ultra-sensitive” new blood test able to predict if breast cancer will return, years before the disease shows up on scans, and thousands of NHS cancer patients in England having access to trials of a new treatment using personalised vaccines to fight their disease. Also stepping up to the plate were weight-loss drugs, which researchers say can help cut cancer rates in obese individuals.
Lung cancer
Physicians are hailing “off the chart” trial results showing that a new drug stopped lung cancer from advancing – for far longer than any other treatment in medical history – with 60% of the patients still being alive after five years, and no progression.
Lung cancer is the world’s leading cause of cancer death, accounting for about 1.8m deaths every year, The Guardian reports. Survival rates in those with advanced forms of the disease, where tumours have spread, are particularly poor.
In the trial, more than half of patients (60%) diagnosed with advanced forms of lung cancer who took lorlatinib were still alive five years later with no progression in their disease, data presented at the world’s largest cancer conference showed. The rate was 8% in patients treated with a standard drug, the researchers found.
The results, presented at ASCO on Sunday, are the longest progression-free survival (PFS) outcomes ever recorded in patients with non-small cell lung cancer, the world’s most common form of the disease.
“To our knowledge these results are unprecedented,” said the study’s lead author, Dr Benjamin Solomon, a medical oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia.
In the phase 3 trial, 296 patients with advanced forms of non-small cell lung cancer were randomly assigned to receive either lorlatinib (149 patients) or crizotinib (147 patients, of whom 142 ultimately received treatment).
Just more than half of the patients were women. In about 25% of them their lung cancer had already spread to the brain when the study began.
The participants all had ALK-positive non-small cell lung cancer. Lorlatinib and crizotinib are both ALK tyrosine kinase inhibitors (TKIs). ALK TKIs are targeted treatments that bind to the ALK protein found in ALK-positive non-small cell lung cancer and stop the growth of tumour cells.
“Despite significant advancements with newer generation ALK TKIs, the majority of patients treated with second-generation ALK TKIs will have progression of their disease within three years,” said Solomon.
“Lorlatinib is the only ALK TKI that has reported five-year progression-free survival, and even after this time, the majority of patients continue to have their disease controlled, including control of disease in the brain.”
The five-year progression-free survival (PFS) rate was 60% in patients who took lorlatinib and 8% in the crizotinib group.
“You don’t need a magnifying glass to see the difference between these two drugs,” said Dr Julie Gralow, Asco’s chief medical officer, adding that 60% five-year progression-free survival in non-small cell lung cancer “is just unheard of”.
Dr David Spigel, the chief scientific officer of the Sarah Cannon Research Institute in London, a world-leading clinical trials facility specialising in new therapies for cancer patients, welcomed the findings. “These long-term data results are off the chart,” he said.
Most of the patients experienced some side-effects. Treatment-related issues occurred in 77% of patients on lorlatinib and in 57% of patients on crizotinib. The most common side-effects reported in the trial that was funded by Pfizer were swelling, high cholesterol and elevated lipid levels.
Cancer Research UK’s chief clinician, Professor Charles Swanton, who was not involved with the study, said the “groundbreaking” results would offer fresh hope for patients with advanced lung cancer.
“Despite progress in our understanding of the disease, it can be incredibly challenging to control cancers that have spread, and there are limited treatment options for lung cancer,” he said.
“Showcasing the power of cancer-growth blocker drugs, this study could present us with an effective way of stopping cancer in its tracks and preventing it from spreading to the brain.
“The results show that over half of the patients who took lorlatinib did not suffer a progression in their disease after five years. In contrast, more than half of the patients who took crizotinib experienced disease progression after just nine months.
“Research like this is vital to find new ways to treat lung cancer and help more people survive for longer.”
GSK drug slashes blood cancer death risk
In other significant trials, the multiple myeloma drug Blenrep from GSK nearly halved the risk of disease progression or death compared with standard-of-care treatments for the incurable blood cancer, showed data from a late-stage study presented at ASCO.
In the trial of 302 patients with relapsed or difficult-to-treat multiple myeloma, 71% of those who received Blenrep in combination with the steroid dexamethasone and pomalidomide were alive without their disease worsening at the end of a year, reports Reuters.
That compared with progression-free survival (PFS) of 51% of those who were treated with pomalidomide, dexamethasone and bortezomib.
Pomalidomide is a generic version of Bristol Myers Squibb’s Pomalyst, while bortezomib is the generic of Takeda Pharmaceuticals’ Velcade.
“Being able to offer a drug like Blenrep that is administered on an outpatient basis, does not require hospitalisation, can be available in a community setting and is not restricted by manufacturing challenges, like cell therapies, is really important,” said GSK oncology executive Hesham Abdullah.
Blenrep has had several setbacks over the past couple of years, including being pulled from the lucrative US market in 2022 after it failed to show superiority over an existing treatment in a separate late-stage study.
The top-line data from this trial – released in March – showing it had met the main goal of significantly improving PFS over a current standard treatment regimen, appeared to signal a comeback for the drug.
More than half of the Blenrep patients were alive without disease progression after a median follow-up of 21.8 months compared with 12.7 months PFS for the standard of care, the company said.
The British drugmaker plans to file marketing applications with global regulators in the second half of 2024.
Good news for breast cancer
AstraZeneca and Daiichi Sankyo’s drug Enhertu slowed the progression of breast cancer by about five months in women whose disease worsened after endocrine therapy – even if they had very low levels of the mutant protein targeted by the drug, according to trial results, also announced on Sunday at ASCO.
The findings significantly broaden the range of breast cancer patients who could benefit from Enhertu, an antibody-drug conjugate designed to deliver toxic chemotherapy directly to tumours.
The data showed an “unprecedented” improvement in progression-free survival, supporting the thesis that antibody-drug conjugates can deliver their payloads more specifically to cancer cells, ASCO president Dr Lynn Schuchter told Reuters.
Study participants given Enhertu lived for a median of 13.2 months before their cancer worsened, compared with 8.1 months for those given chemotherapy.
Results were similar for patients with low and “ultra-low” levels of HER2 – the protein targeted by the drug.
About 70% of breast cancer cases are hormone-receptor positive, and are initially treated with endocrine drugs that interfere with hormones like oestrogen. If the cancer worsens, the only current option for those patients is chemotherapy. Another 20%-25% of breast cancers are HER2 positive, or HER2 “high”, and can be treated with drugs like Roche’s Herceptin.
Enhertu is currently approved as a second-line treatment for HER2 positive and HER2 low breast cancer.
If approved for HER2 low and ultra-low breast cancers after endocrine therapy, eight out of out 10 women with metastatic breast cancer could be treated with Enhertu, said oncology research chief Susan Galbraith.
As tumour mutation testing improves, the number of patients with no HER2 could be so small that Enhertu becomes a preferred choice for almost all patients in approved settings.
Galbraith said Astra was working with global regulatory agencies to submit the latest Enhertu breast cancer data.
A number of other trials are under way aimed at moving the drug into earlier lines of therapy.
Galbraith said Enhertu was effective at reaching tumours with low levels of HER2 due to the mechanism linking the antibody to the drug.
“Our linker is stable in the blood. When it gets to the tumour it gets cleaved and then it can go across the cell membrane,” she added.
Blood test ‘can predict’ breast cancer return
British researchers say their “ultra-sensitive” new blood test is able to predict if breast cancer will return – years before the disease shows up on scans – after conducting trials on 78 patients with early blood cancer.
They said the test picks up traces of a tumour’s DNA before a full relapse and was found to be 100% accurate at predicting which patients would see their cancer come back.
They hope the test can enable earlier treatment and improved survival rates.
The team from the Institute of Cancer Research (ICR) London conducted the trial on 78 patients with different types of early breast cancer, with the “liquid biopsy” searching for 1 800 mutations in the patients’ blood which are released by cancer cells.
These circulating tumour DNA were found in 11 women, all of whom saw their cancer relapse. None of the others saw their cancer return.
On average, the blood test detected cancer 15 months before symptoms appeared or the illness showed up on scans, according to their results presented at ASCO.
The earliest detection was 41 months before a scan confirmed the diagnosis, reports the BBC.
Lead researcher Dr Isaac Garcia-Murillas, from the ICR, said: “Breast cancer cells can remain in the body after surgery and other treatments but there can be so few of these that they are undetectable on follow-up scans.”
These cells can then cause patients to relapse many years after their initial treatment.
He said the study laid the groundwork for better post-treatment monitoring and potentially life-extending treatment.
Researchers tested blood samples at the point of diagnosis, then again after surgery and chemotherapy, repeating the tests every three months for the next year and every six months for the next five years.
Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, which part-funded the study, said: “Early detection is one of our greatest weapons against breast cancer and these initial findings, which suggests new tests could be able to detect signs of breast cancer recurrence more than a year before symptoms emerge, are incredibly exciting.”
Though the research was still in its infancy, he said catching breast cancer recurrence earlier means treatment is likelier to destroy the cancer and prevent its spread to other parts of the body, thus becoming incurable.
It is unclear when the test could become widely available.
Weight loss drugs shrink tumours
Also featuring at the conference were weight-loss drugs, which have been shown to cut cancer risk by a fifth, and which doctors said now offer a new weapon in the global fight against cancer, with “enormous potential” to prevent new cases and shrink tumours.
Injections like Wegovy, which have revolutionised obesity treatment, were also recently approved for use in other areas of medicine, including reducing the risk of heart attacks, strokes and cardiovascular-related deaths.
Now experts believe the drugs could play a big role in preventing and treating cancer.
A study presented at the conference found patients taking the drugs were 19% less likely to develop 13 obesity-related cancers, including ovarian, liver, colorectal, pancreatic, bowel and breast cancer, reports The Guardian.
The research involving 34 000 people, led by the Case Western Reserve University in Ohio, also found patients were half as likely to die over 15 years compared with patients not taking the jabs, also known as GLP-1 receptor agonists (RA).
Study co-authors Dr Cindy Lin and Dr Benjamin Liu said: “Our findings are significant in that they could change the paradigm of obesity management by suggesting early intervention with GLP-1 RAs could delay or prevent obesity-related cancer development.”
There could be “multiple” ways in which the drugs cut the risk of cancer – not just by helping people to lose weight, they added.
A second study published at the event suggested weight-loss drugs could reduce the risk of cancer coming back in breast cancer patients – and boost their prospects of long-term survival.
Researchers from Memorial Sloan Kettering Cancer Centre in New York said the jabs could cut the risk of cancer recurrence and be a “new tool” against the disease.
A third paper led by Yale University, also looking at breast cancer patients, suggested taking weight-loss drugs reduced the chances of the disease returning.
Speaking at the conference, Dr Mitchell Lazar, the director of the institute for diabetes, obesity and metabolism at the University of Pennsylvania School of Medicine, said: “GLP-1 based therapies are highly effective at producing weight loss, and thus one of the fundamental mechanisms by which they improve cancer outcomes is via the impressive weight loss that they produce.
“Obesity is a risk factor for nearly all cancers, in both men and women. So the revolution in the medical treatment of obesity has enormous potential to prevent new cancers, reduce the severity and growth rate of existing tumours, and synergise with new cancer-specific therapies.”
Dr Jennifer Ligibel, a senior physician at Dana-Farber Cancer Institute who was not involved with the studies, said: “These are exciting, preliminary findings of a link between use of GLP-1 RAs and cancer risk.”
They added to previous work suggesting the drugs could reduce cancer risk, she added.
A previous study showed they were associated with a 50% reduced risk of bowel cancer in people with type 2 diabetes. “Individuals with diabetes who were prescribed a GLP-1 RA had a lower risk of colorectal cancer compared with others who were not prescribed one of these drugs,” Ligibel said.
Dr Julie Gralow, the chief medical officer of ASCO, said the evidence was not clear yet whether the potential benefits of weight-loss drugs in reducing cancer risk were just as a result of weight loss, or whether there were other, unknown factors at play.
Gralow, a world-renowned cancer expert who was named woman oncologist of the year in 2023, said she was absolutely certain the jabs would become a much greater focus of cancer prevention research in the future. “The more we can do to reduce the risk factors and prevent cancer, the better,” she added.
ASCO presentation – Comparative risk of obesity-related cancer with glucagon-like protein-1 receptor agonists vs. bariatric surgery in patients with BMI ≥ 35 (Open access)
https://meetings.asco.org/abstracts-presentations/238997
ASCO presentation – Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer (Open access)
https://meetings.asco.org/abstracts-presentations/231445
JAMA Oncology article – GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients With Type 2 Diabetes, With and Without Overweight/Obesity
https://jamanetwork.com/journals/jamaoncology/fullarticle/2812769
The Guardian article – ‘Enormous potential’: weight-loss drugs cut cancer risk by a fifth, research shows (Open access)
https://www.theguardian.com/society/article/2024/jun/04/weight-loss-drugs-cut-cancer-risk-fifth-research-wegovy
At-home spit test may ID prostate cancers
In another ASCO presentation, British researchers said their preliminary findings have suggested that saliva tests carried out at home were better at identifying men who are at higher risk of prostate cancer than the standard blood test.
The DIY could identify genetic factors making men more likely to develop the disease, which claims around 12 000 lives a year in the UK, reports the BBC.
The study was carried out by the Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, who hoped the findings could “turn the tide on prostate cancer”.
The UK does not have a national screening programme for prostate cancer because blood tests are not considered accurate enough and can pick up non-life threatening forms of the disease over aggressive types.
However, researchers believe the cheap and simple testing method could help catch the disease earlier and save lives, said Ros Eeles, principal investigator for the study and a professor at the ICR, as well as a consultant at the Royal Marsden NHS Foundation Trust.
“It is simple from the patient’s point of view… get sent a tube, put your saliva sample into it and post it off,” said consultant urologist Professor Caroline Moore.
“DNA is extracted from that (saliva) and analysed to look for a combination of genetic variations linked to prostate cancer.”
The study had involved more than 6 000 European men aged 55-69, an age bracket where the risk of developing prostate cancer is increased.
The researchers then used blood and saliva tests on a smaller group of those men who were found to have genetic variations in their DNA indicating a higher likelihood of developing the disease.
Preliminary results from the research showed the saliva test produced fewer false positives and picked up a higher proportion of aggressive cancers.
Currently, men who wish to be tested for prostate cancer need to speak to their GP and have a blood test, which measures the level of prostate-specific antigen (PSA) in their blood.
“But we know the PSA test doesn’t find all of the cancers,” Moore said, adding the men in the study had done the test, but showed normal PSA levels.
After an MRI scan and biopsy, 40% of men with high scores from the saliva test were diagnosed with prostate cancer.
For standard blood tests, only 25% of men with a high PSA level will actually have prostate cancer, the researchers said.
Institute of Cancer Research chief executive Professor Kristian Helin said the standard blood test “can cause men to go through unnecessary treatments and, more worryingly, it’s missing men who do have cancer”.
Moore said the next step would be a big screening study to find the best test or the best combination of tests, looking at saliva tests, PSA tests and MRI scans, which are a modern alternative to the rectal examination.
Personalised cancer vaccines
Delegates also heard that thousands of patients in England will be fast-tracked into ground-breaking trials of personalised cancer vaccines in a world-first NHS “matchmaking” scheme to save lives.
The jabs, a form of immunotherapy, aim to provide a permanent cure and are custom-built for each patient in just a few weeks. They are tailored to the individual’s tumours and work by telling their body to hunt and kill any cancer cells and prevent the disease from coming back.
Unlike vaccines that protect from an infection, like the Covid-19 jab, these vaccines treat people who already have the disease, reports The Guardian.
To make them, a sample of a patient’s tumour is removed during surgery, followed by DNA sequencing and in some cases the use of artificial intelligence. The result is a personalised anti-cancer jab specific to that patient’s tumour.
Patients who meet the eligibility criteria and agree to have a blood test and sample of their cancer tissue analysed will gain immediate access to clinical trials for the new vaccines that experts say represent a new dawn of treatments for cancer.
Research into cancer vaccines is at an early stage, but trials have already shown they can be effective at killing off any remaining tumour cells after surgery and dramatically cutting the risk of cancer returning.
The NHS has enrolled dozens of patients on to its scheme, the Cancer Vaccine Launch Pad, with thousands more to be enlisted at 30 NHS sites across England. The first trials are expected to focus on colorectal, skin, lung, bladder, pancreatic and kidney cancer, officials said, but other forms of the disease could be added in future.
“As more of these trials get up and running at hospitals across the country, our national matchmaking service will ensure as many eligible patients as possible get the opportunity to access them,” head of NHS England Amanda Pritchard said.
German biotech company BioNTech, one of those that is partnering with the NHS on the trials, presented new preliminary data on how measuring circulating tumour DNA could help increase early detection of colorectal cancer.
Iain Foulkes, executive director of research and innovation at Cancer Research UK, said it was “incredibly exciting” that patients were accessing personalised jabs in a development that will be a “gamechanger” in the fight against cancer. “Clinical trials like this are vital in helping more people live longer, better lives, free from the fear of cancer,” he said.
The first NHS patient to join the Cancer Vaccine Launch Pad is Elliot Pfebve (55) a lecturer at Coventry University who had no symptoms and was diagnosed with colorectal cancer after a routine health check. He had surgery to remove his tumour and 30cm of his large intestine, followed by chemotherapy.
Pfebve then received his personalised cancer vaccine at University Hospitals Birmingham NHS foundation trust, one of several sites taking part in the BioNTech colorectal cancer vaccine trial. It was designed with the same mRNA technology used to create the Pfizer/BioNTech Covid vaccine.
His vaccine was created by analysing his tumour to identify mutations specific to his cancer. Doctors then used this data to create a personalised cancer vaccine.
The trial’s principal investigator, Dr Victoria Kunene, said it was too early to say if Pfebve had been cured completely, but said she was “extremely hopeful”.
“Based on the limited data we currently have of the in-body response to the vaccine, this could prove to be a significant and positive development for patients, but more data are needed and we continue to recruit suitable patients to the trial to establish this further.”
Cancer vaccines are designed to induce an immune response that may prevent cancer from returning after surgery to remove tumours, by stimulating a patient’s immune system to recognise and destroy any remaining cancer cells – and stop them coming back.
Professor Peter Johnson, NHS England’s national clinical director for cancer, said: “We know that even after a successful operation, cancers can sometimes return because a few cancer cells are left in the body, but using a vaccine to target those remaining cells may be a way to stop this happening.”
More research is needed to get a full picture of how well the jabs work and which cancers they could treat, but experts believe they could be effective in a range of cancers, including but not limited to colorectal, lung, bladder, pancreatic and kidney.
If successfully developed, researched and approved, they could become part of standard care.
Vaccines have revolutionised medicine, protecting millions of people from measles and mumps, polio and coronavirus. They have also wiped out smallpox, one of the deadliest diseases in human history.
Scientists believe they can form part of the toolbox needed to fight off cancer for good, and while they will not replace surgery, chemotherapy or radiotherapy any time soon, they could play a key role in immunotherapy, the fourth weapon against cancer.
Doctors have also begun trialling the world’s first personalised mRNA cancer vaccine for melanoma. Experts hailed its potential to permanently cure the skin cancer. A phase 2 trial found that the vaccines dramatically reduced the risk of the cancer returning in melanoma patients.
Study details
Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study.
Benjamin Solomon, Geoffrey Liu, Todd Michael Bauer et al.
Presented at ASCO on 31 May 2024
Background
Lorlatinib, a brain-penetrant, 3rd-generation ALK tyrosine kinase inhibitor, demonstrated improved progression-free survival (PFS) and intracranial (IC) activity vs crizotinib in the phase 3 CROWN study in treatment-naïve patients (pts) with advanced ALK+ non-small cell lung cancer (NSCLC). We report long-term efficacy and safety outcomes from the CROWN study after five years of follow-up.
Methods
296 treatment-naïve pts with advanced ALK+ NSCLC were randomized 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). In this post hoc analysis, we present investigator-assessed efficacy outcomes, safety, and biomarker analyses. Formal statistical testing was not performed.
Results
As of October 31, 2023, 74 of 149 pts (50%) vs 7 of 142 pts (5%) were still receiving lorlatinib vs crizotinib. With a median duration of follow-up for PFS (95% CI) of 60.2 months (57.4-61.6) in the lorlatinib and 55.1 months (36.8-62.5) in the crizotinib arm, median PFS (95% CI) was not reached (NR; 64.3-NR) with lorlatinib and 9.1 months (7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.27). 5-year PFS (95% CI) was 60% (51-68) with lorlatinib and 8% (3-14) with crizotinib. Median time to IC progression (95% CI) was NR (NR-NR) with lorlatinib and 16.4 months (12.7-21.9) with crizotinib (HR, 0.06; 95% CI, 0.03-0.12). In pts without baseline brain metastases in the lorlatinib arm, only 4 of 114 developed brain progression, occurring within the first 16 months of treatment. Efficacy outcomes by baseline brain metastases are shown in the Table. Grade 3/4 adverse events (AEs) occurred in 77% of pts with lorlatinib and in 57% of pts with crizotinib. Treatment-related AEs led to treatment discontinuation in 5% and 6% of pts in the lorlatinib and crizotinib arms, respectively. Safety profile was consistent with that observed in prior analyses. Emerging new ALK mutations were not detected in circulating tumor DNA collected at the end of lorlatinib treatment (n = 31).
Conclusions
After five years of follow up, the median PFS in the lorlatinib arm has yet to be reached, corresponding to the longest PFS ever reported in advanced NSCLC. Coupled with prolonged IC efficacy and absence of new safety signals, these results indicate an unprecedented improvement in outcomes for pts with advanced ALK+ NSCLC.
Study details
Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma
Vania Hungria, Pawel Robak, Marek Hus et al for the DREAMM-7 Investigators
Published in the New England Journal of Medicine on 1 June 2024
Abstract
Background
Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies.
Methods
In this phase 3, open-label, randomised trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)–negative status.
Results
In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved.
Conclusions
As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events.
Study details
Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06).
Giuseppe Curigliano, Xichun Hu, Aditya Bardia et al.
Presented at ASCO on 2 June 2024
Background
T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC.
Methods
Pts with HER2-low or -ultralow, HR+ mBC were randomised 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety.
Results
As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC.
Conclusions
T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC.
Reuters article – Astra’s Enhertu breast cancer trial shows ‘unprecedented’ results (Open access)
BBC article – New blood test 'can predict' breast cancer return (Open access)
BBC article – At-home saliva test may catch deadly prostate cancers (Open access)
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