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The addition of temozolomide (Temodar) to radiotherapy improved overall survival (OS) and progression-free survival (PFS) vs radiotherapy alone in patients with IDH-mutant, symptomatic or progressive low-grade glioma (LGG) without codeletions of 1q and 19q, as well as patients with codeletions, according to findings from a molecular analysis of the phase 3 ECOG-ACRIN E3F05 trial (NCT00978458), which were presented at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting.¹

A statistically significant OS benefit with the addition of temozolomide to radiotherapy vs radiotherapy alone was seen among patients with IDH-mutated disease without codeletions (n = 38; HR, 0.15; 95% CI, 0.03-0.74; stratified log-rank P = .02). An OS benefit was also seen among patients with codeletions (n = 74; HR, 0.51; 95% CI, 0.19-1.42). Numerical PFS benefits were also seen among patients without codeletions (HR, 0.50; 95% CI, 0.16-1.54) and those with codeletions (HR, 0.57; 95% CI, 0.24-1.35).

“These numbers were too small to allow us to declare statistical significance,” lead study author David Schiff, MD, said of the findings in the population of patients with codeletions during the presentation.

Schiff is the Harrison Distinguished Professor of Neurology, Neurological Surgery and Medicine in the Department of Neurology, Division of Neurology at the University of Virginia (UVA), as well as the codirector of the UVA Neuro-Oncology Center in Charlottesville.

ECOG-ACRIN E3F05 Trial Key Highlights

• The ECOG-ACRIN E3F05 trial investigators performed methylation profiling to determine IDH mutational status in enrolled patients following trial closure.

• The addition of temozolomide to radiotherapy provided a statistically significant OS benefit compared with radiotherapy alone for patients with IDH-mutant LGG who did not have codeletions of 1q and 19q (HR, 0.15; 95% CI, 0.03-0.74; stratified log-rank P = .02).

• Among patients with IDH-mutated, non-codeleted disease, the 10-year OS rate was higher in the temozolomide plus radiotherapy arm (80%) compared with the radiotherapy alone arm (39%).

What was the design of the ECOG-ACRIN E3F05 trial?

E3F05 enrolled patients at least 18 years of age with grade II glioma who had receive no prior radiotherapy or chemotherapy. Patients also needed to be younger than 40 years of age or have radiographic progression or have uncontrolled symptoms/seizures. Following surgery, patients were randomly assigned to receive radiotherapy at 50.4 Gy alone or with concomitant temozolomide followed by 12 cycles of temozolomide on days 1-5 of each 28-day cycle. After study treatment, patients underwent follow-up.

Patients were stratified by age, deletion 1q/19q status, Karnofsky performance score, tumor diameter, and contrast enhancement.

How has the E3F05 trial evolved as glioma classification systems have changed over time?

The E3F05 trial was activated in September 2009, which Schiff noted was prior to the advent of IDH testing in glioma. In January 2014, updated findings from the phase 2 RTOG 9802 trial (NCT00003375) of radiation with or without procarbazine/lomustine/vincristine chemotherapy in patients with LGG showed a benefit with the addition of chemotherapy, making the control arm of E3F05 unethical. At that point, accrual to E3F05 was stopped with 172 of the planned 540 patients enrolled.

“These non-codeleted tumors were agnostic as to their IDH [mutation] status and were 2 World Health Organization classification systems past what we started with when the study was conceived,” Schiff explained. “To try to ascertain IDH mutational status to characterize…patients according to contemporary neuropathology, we reached an agreement with the National Cancer Institute…database group to perform methylation profiling on our patients.”

Among the 172 enrolled patients, 74 had codeletions. Additionally, 97 patients had adequate samples for methylation profiling, 52 of whom did not have codeletions. Among those 52 patients, Heidelberg v12 classification was used to determine that 13 had IDH wild-type disease (diffuse high-grade subtype F, n = 3; glioblastoma, n = 2; ganglioglioma, n = 2), and 38 had IDH-mutant diffuse glioma (IDH-mutant low-grade astrocytoma, n = 36; IDH-mutant high-grade astrocytoma, n = 2).

What efficacy data from E3F05 have been previously reported?

Efficacy findings that were previously reported at SNO 2024 showed that the addition of temozolomide to radiotherapy significantly improved OS vs radiotherapy alone (HR, 0.54; 95% CI, 0.31-0.95).² OS benefits were also seen among patients with codeletions of 1q and 19q (HR, 0.56; 95% CI, 0.20-1.60) and those with 1 or both of these intact (HR, 0.53; 95% CI, 0.27-1.04). Numerical PFS benefits were also seen in the overall population (HR, 0.76; 95% CI, 0.44-1.28), those with codeletions (HR, 0.63; 95% CI, 0.24-1.64), and those with 1 or both intact (HR, 0.82; 95% CI, 0.43-1.56).

What additional updated efficacy data from E3F05 were presented at SNO 2025?

Among the patients with IDH-mutated, non-codeleted disease, the 5-year PFS rate was 76% in the temozolomide arm vs 53% in the radiotherapy alone arm.¹ The 10-year PFS rate with temozolomide was 59%. At 5 years, the OS rates were 94% with temozolomide plus radiotherapy and 71% with radiotherapy alone. These respective rates at 10 years were 80% and 39%.

“The benefit of adding temozolomide in the IDH-mutant astrocytomas is particularly evident when you look at 10-year OS with radiation alone,” Schiff added.

Among the patients with codeletions, the 5-year PFS rate was 79% in the temozolomide arm vs 64% in the radiotherapy alone arm. The 10-year PFS rates in these respective arms were 47% and 69%. At 5 years, the OS rates were 97% with temozolomide plus radiotherapy and 92% with radiotherapy alone. These respective rates at 10 years were 90% and 68%.

“In summary, we’ve shown a statistically significant OS benefit with the addition of temozolomide to radiation in grade 2 IDH-mutant astrocytomas, and we still see a trend toward [an] OS benefit in the oligodendrogliomas as well,” Schiff concluded. “We [also] see suggestive HRs for PFS in both the astrocytomas and oligodendrogliomas.”

References

1. O’Neill A, Brown P, et al. Molecular analysis of outcomes in ECOG-ACRIN E3F05: phase III study of radiation therapy with or without temozolomide of symptomatic or progressive low-grade gliomas. Presented at: 2025 SNO Annual Meeting; November 19-23, 2025; Honolulu, Hawaii. Abstract CTNI-29.
2. Schiff D, O’Neill A, Brown P, et al. LTBK-07. Progression-free and overall survival results of ECOG-ACRIN E3F05: a phase 3 intergroup trial of radiation ± temozolomide for grade II gliomas.Neuro Oncol. 2024;26(suppl 8):viii1-viii2. doi:10.1093/neuonc/noae165.1303

For generations of women, the logic has seemed airtight: Focus on a career in your 20s, and worry about starting a family once you are established in a job.

This mindset has catapulted women into higher-earning positions, and into traditionally male-dominated fields. The share of women in their prime working years who are in the workforce is around a record high. And women are having babies later, if they have them at all. The answer to fertility constraints, they’re told, is egg freezing.

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Okta (OKTA) has been catching investors’ attention lately, as its stock price has seen a dip of nearly 10% over the past month. This movement has prompted fresh discussion about the company’s current valuation and future prospects.

See our latest analysis for Okta.

Zooming out, Okta’s 1-year total shareholder return is up just 2.8% even as the stock price has given back nearly 10% this month. This shows that momentum has faded after a volatile stretch of gains and setbacks. Most recently, the company saw its share price return slip by 14.5% over the last 90 days, which could reflect investors recalibrating expectations around its growth potential and risk profile.

If you’re curious to see what other growth stories are developing beyond Okta, now’s a smart moment to check out fast growing stocks with high insider ownership.

With shares lagging and trading at a notable discount to analyst price targets, the question now is whether Okta’s current weakness signals an undervalued opportunity or if the market already reflects all of its potential upside.

Compared to Okta’s last close at $78.68, the most popular narrative pegs fair value above $120. This supports a bold thesis centered on cloud identity growth and increasing security needs.

The proliferation of AI agents and nonhuman identities is creating new, urgent security use cases that require sophisticated identity governance, privileged access management, and policy controls. These are areas where Okta is innovating (Cross App Access, Auth0 for AI Agents, Axiom acquisition), opening incremental growth avenues and potential margin expansion through higher-value and differentiated products.

Read the complete narrative.

Want to know what financial forecasts power this striking discount? The foundation here is aggressive profit expansion, ambitious margin targets, and revenue acceleration that could catch the market off guard. Find out which key growth bets and financial leaps are at the heart of this narrative. Are the numbers bold enough to deliver on the massive upside?

Result: Fair Value of $120.37 (UNDERVALUED)

Have a read of the narrative in full and understand what’s behind the forecasts.

However, ongoing cybersecurity consolidation and execution risks from frequent product expansions could quickly challenge Okta’s growth story if there are any missteps in integration or innovation.

Find out about the key risks to this Okta narrative.

Shifting focus from growth assumptions to how the market values Okta compared to its peers shows a less optimistic picture. Okta currently trades at a price-to-earnings ratio of 82.6x, notably higher than the US IT industry average of 27.8x and its peer average of 28.1x. The fair ratio for Okta, based on broader trends, stands at just 40.7x. This sizable gap could indicate more downside risk if investor sentiment reverts to the mean. Are markets getting ahead of themselves, or will Okta’s earnings prove robust enough to justify such a premium?

See what the numbers say about this price — find out in our valuation breakdown.

If you have a different perspective or want to dig into the numbers yourself, you can build your own viewpoint in just a few minutes, your way. Do it your way.

A good starting point is our analysis highlighting 4 key rewards investors are optimistic about regarding Okta.

There’s no reason to limit yourself to just one opportunity. Use the Simply Wall Street Screener and uncover unique stocks before others even notice.

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include OKTA.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

• Earlier in November 2025, Restaurant Brands International announced a joint venture with Chinese asset manager CPE to grow Burger King’s restaurant count in China from about 1,250 to more than 4,000 locations by 2035, backed by a US$350 million investment from CPE.

• This move aligns with RBI’s strategy of expanding via franchise-led models and underlines the significance of China’s rapidly growing consumer market for global quick-service restaurant brands.

• We’ll consider how this ambitious partnership and expansion plan could influence the company’s investment narrative and future growth opportunities.

Outshine the giants: these 25 early-stage AI stocks could fund your retirement.

To be a shareholder in Restaurant Brands International, you need to believe in the company’s ability to drive profitable growth through its global franchise model, while balancing the risks of international expansion and margin pressures. The recent China joint venture is a meaningful step for long-term unit growth but, in the near term, does not materially resolve the biggest risk: the potential for margin compression from persistent commodity inflation and competitive discounting, especially in the key U.S. and international markets.

The recently completed US$1.21 billion follow-on equity offering stands out in the context of these expansion plans. This fresh capital further strengthens RBI’s ability to fund initiatives like the ambitious China partnership, reinforcing the company’s commitment to international growth as a primary catalyst, while also highlighting the need for disciplined capital allocation should near-term pressures on margins intensify.

By contrast, investors should be aware that executing large-scale international growth ventures can introduce risks that…

Read the full narrative on Restaurant Brands International (it’s free!)

Restaurant Brands International’s outlook anticipates $10.1 billion in revenue and $2.0 billion in earnings by 2028. This is based on a 3.5% annual revenue growth rate and a $1.1 billion increase in earnings from the current $862.0 million.

Uncover how Restaurant Brands International’s forecasts yield a $78.25 fair value, a 11% upside to its current price.

Simply Wall St Community fair value estimates for Restaurant Brands International range from US$43 to nearly US$87 across 4 separate perspectives. While these views underscore broad uncertainty, the recent China expansion plans highlight that international initiatives can significantly shape future performance, reminding you to explore several alternative viewpoints before making up your mind.

Explore 4 other fair value estimates on Restaurant Brands International – why the stock might be worth 39% less than the current price!

Disagree with existing narratives? Create your own in under 3 minutes – extraordinary investment returns rarely come from following the herd.

Our top stock finds are flying under the radar-for now. Get in early:

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include QSR.

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

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‘From niche wellness corners into the mainstream’

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‘An add-on, not a magic fix’

The government is expected to announce an extra £1.3bn in funding for a scheme encouraging the use of electric vehicles (EVs) at next week’s Budget.

The Electric Car Grant scheme started in July as part of the move to zero emission vehicles. The government says it has helped 35,000 switch to EVs.

However, early research suggests there is little indication the scheme has attracted entirely new buyers.

There will also be money to create more charging points, and a consultation on helping people without driveways to charge their cars.

It is also possible EV owners could face a new tax elsewhere in Wednesday’s Budget in the form of a pay-per-mile charge in future.

All new cars will have to be electric or hybrid from 2030, when a ban on the sale of new petrol and diesel cars comes into force.

The Electric Car Grant scheme, which provides a discount of up to £3,750 on eligible vehicles, was launched with an initial fund of £650m.

New AutoMotive, a non-profit organisation supporting the UK’s transition to electric vehicles, found in a recent study that the scheme had yet to expand the market for EVs.

EVs covered by the scheme made up 23.8% of new registrations in September, the same as their share before the Electric Car Grant was announced, New Automotive said.

“It isn’t yet clear that it’s prompting consumers to consider buying cars that they wouldn’t have gone ahead and bought anyway,” David Farrar, policy manager for New AutoMotive, said at the time.

The Budget is also expected to announce a further £200m for speeding up the rollout of chargepoints across the UK.

Data from Zapmap shows almost 87,000 points across the UK, in about 44,000 locations. Those include places like supermarket car parks and lamppost chargers.

“The proposed funding will support the creation of thousands of chargepoints and provide extra resources for local authorities to ramp up charging infrastructure on local streets – making it easier for everyone to access reliable charging, including those without off-street parking,” the government said.

Chancellor Rachel Reeves, it added, was “expected to publish a consultation on Permitted Development Rights to make it easier and cheaper for people without a driveway to charge”.

However, it is also possible that EV owners could face a new tax in the Budget in the form of a pay-per-mile charge from 2028.

A government spokesperson told the BBC earlier this month: “Fuel duty covers petrol and diesel, but there’s no equivalent for electric vehicles. We want a fairer system for all drivers.”

Reeves is being urged not to raise taxes on drivers overall, with campaigners preparing to deliver a petition to Downing Street early next week which calls for fuel duty, long frozen, not to be increased.

Richard Holden, the shadow transport secretary, said that “handing out £1.5 billion in EV subsidies while hard-working taxpayers are squeezed dry” was “madness”.

“Ordinary families are facing increased taxes and spiralling inflation under Labour, yet the Government’s priority is handing out discounts on new electric cars,” the Conservative MP said.

Reeves is expected to increase some taxes in the Budget after saying she means to bring down NHS waiting lists, the national debt and the cost of living.

America’s most popular car brand is recalling more than one million vehicles (1).

On Oct. 30, Japanese vehicle manufacturer Toyota announced a sweeping recall of several models released between 2020 and 2023 as a result of malfunctioning backup cameras (2). The Toyota Newsroom stated that drivers of some Toyota and Lexus models could experience a blacked out or frozen camera when reversing, a violation of federal car safety standards (3) .

Some of the impacted models include the Camry, Highlander, and Prius. Toyota says affected drivers will be notified of the recall by late December 2025.

A faulty backup camera may not sound like a serious enough issue to send your car into the shop, but companies only issue recalls after receiving customer complaints and when there’s a verified safety risk (4). A malfunctioning backup camera can fail to alert drivers to obstacles, animals, or children in the rear of the car, and creates an additional blind spot for drivers of newer vehicles who aren’t used to having to look behind or check their mirrors when backing up (5).

It’s a hassle to deal with a vehicle that has been recalled, but it’s important to get the issue fixed. Here’s what drivers need to know.

Recalls are not uncommon: nearly 30 million vehicles in the U.S. were impacted by nearly 1,100 different recalls in 2024, according to the National Highway Traffic Safety Administration (6) .

If a driver is alerted to a recall, they should schedule service with the car dealership as soon as possible, especially if the issue presents a severe safety risk. Some recalls, like a faulty camera, may not present immediate risks. In this case, Toyota isn’t issuing notices to impacted drivers until December. But sometimes, your car might need an urgent fix.

Fortunately, it’s the manufacturer’s responsibility to pay for the fix. But returning your car to the road isn’t always smooth.

Car makers may announce a fix is needed before they are actually ready to make the repairs.

Trending: Warren Buffett used 8 simple money rules to turn $9,800 into a stunning $150B — start using them today to get rich (and then stay rich)

According to Michael Crossen, lead auto technician at Consumer Reports, “Automakers may announce a recall before they’ve figured out how to handle the problem, because of federal reporting requirements. “

“If that happens, you’ll have to wait for a second notice to tell you that a repair is ready.”

Plus, since hundreds of thousands of vehicles will at least theoretically be going into dealerships for the same issue, there’s a chance the required part won’t be available, or that the next open appointment time isn’t as soon as you’d prefer.

What’s most inconvenient to impacted drivers, however, is when a dealership purposely drags their heels on repairs. Raymond Roth, director and automotive recalls practice leader at analysis firm Stout, says that since dealers don’t stand to make money from the recall repair, they might prioritize other work first.

“We have observed some instances of dealers telling vehicle owners that parts are not available when they actually were, because (the dealerships) viewed other repair work as being more profitable,” Roth told Consumer Reports (7).

If you have an impacted vehicle, the notice will probably come in the mail, and you may get more than one. If you receive a recall notice, call your car dealership to schedule the fix. Make sure it’s an authorized dealership that works directly with the recall issuer, and bring the recall letter with you.

And remember, the only cost to you is likely to be the time out of your day. You should consider asking the dealership for a loaner vehicle, especially if the issue has rendered your car undriveable or the repair will take hours or even days.

If your model is listed on a recall but you haven’t received a notice, don’t assume it’s not affected, as manufacturers have 60 days to issue notices (8). If you want to check whether your car has a current recall, you can enter your vehicle identification number (VIN) on the NHTSA’s recall checker (9).

We rely only on vetted sources and credible third-party reporting. For details, see our editorial ethics and guidelines.

Experian (1); USA Today (2); Toyota (3); NHTSA (4); Arnold & Itkin Trial Lawyers (5); NHTSA (6); Consumer Reports (7); Lehigh Valley Acura (8); NHTSA (9)

This article provides information only and should not be construed as advice. It is provided without warranty of any kind.

RAWALPINDI:

The Competition Commission of Pakistan has initiated action against major private schools across the country that sell notebooks, textbooks, uniforms, school ties, girls’ scarves and registers at extremely high prices by simply placing their school logos on them.

The Commission has issued show-cause notices to owners of 17 major private schools, seeking replies within two weeks. The move has been widely welcomed by private school associations, parents, citizen action groups, the District Bar Association, and stationers.

They said issuing notices alone is not enough; the action must be implemented strictly.

They demanded a complete ban on the sale of textbooks, notebooks, uniforms, shoes, ties, and school canteen items through specific shops only.

They stressed that stationery and uniforms for all government and private schools should be available at every open-market shop, which would encourage competition and reduce prices.

The competition commission has summoned the 17 schools within 14 days for selling school-logo textbooks, copies, uniforms and stationery at 200-300 per cent higher prices than the open market.

President of the All Pakistan Private Schools and Colleges Association, Irfan Muzaffar Kayani, said he fully supports the government’s action. He added that franchise schools are forced to sell logo-branded books and uniforms, as it is the decision of the owners, not the franchisees.

The association supports making all textbooks, copies and uniforms available in the open market. He said they provide some relief to students by offering 10 per cent of seats with free education and books.

President of the District Bar Association, Sardar Manzar Bashir, said the Bar and lawyers are taking the matter directly to the Rawalpindi Bench of the High Court, challenging excessive fees, registration charges, and the sale of logo-branded books and uniforms.

The Bar will request the court to set a strict timeline for creating a uniform national policy in consultation with all stakeholders.

Parents Chaudhry Shaukat and Haji Ibrahim said education and health have already become too expensive, and major private schools worsen the burden by selling logo-branded books and uniforms at prices up to 300 per cent higher. Parents, they said, are forced to bear this burden by cutting household expenses.

They warned that if the government limits itself to issuing notices without enforcement, it would also be considered complicit.

Stationer Waseem Ahmed said that just as meat, clothing, lentils, ghee, sugar, chicken, milk, and yoghurt are available in the open market, school textbooks, notebooks, and uniforms must also be sold openly.

This will encourage competition and reduce prices. “We are booksellers and sell items with minimal profit,” he said. Terming it a positive step by the Punjab government, he added that it would bring relief to people already crushed by inflation.