Category: 3. Business

It could be described as a storm in a teacup but the humble Jaffa Cake is once again at the centre of controversy after McVitie’s asked a biscuit museum to pull the snack from a display.

The manufacturer took issue with the orangey treat being showcased in a museum devoted to biscuits because, for VAT purposes anyway, it is officially a cake. This fact was settled long ago in a legal battle with the taxman.

The David and Goliath-style row – which some suggested had been orchestrated by McVitie’s to boost sales – has reignited the debate.

Days after the biscuit museum in Bermondsey, south London, unveiled the display, McVitie’s sent it a cease-and-desist-style letter requesting “the immediate removal of Jaffa Cakes from your biscuit exhibit”.

However, it sought to sweeten the pill by diluting the legalese with biscuit-based puns. “We write to you today, not with crumbs of animosity, but with a full slice of firm objection,” it says. “Allow us to be clear: Jaffa Cakes are, in fact, cakes. Some would say the clue is in the name on the box.”

McVitie’s and the biscuit museum, officially called the Peek Frean Museum, said they were yet to agree on a resolution. The museum’s curator, Gary Magold, said, “It’s a shame – we’ve had to remove the exhibition for the moment. We’re hoping we can reach an agreement.”

The subtleties of the “is it a cake or biscuit?” debate have likely filled many a tea break but the tax law is clear: biscuits are zero-rated, but as soon as the makers start covering them with chocolate they attract 20% VAT. This was at the heart of the Jaffa Cakes case, which came to a head in 1991.

HM Customs & Excise (the predecessor of HMRC) said they were biscuits, and that their chocolatey topping was taxable. The manufacturer McVitie’s insisted they were cakes, which are zero-rated. It won, and those smashing orangey bits can be enjoyed tax-free.

This week’s skirmish lit up social media message boards. One poster tried to shut the debate down, stating: “A biscuit goes soft when you leave it out. A cake goes hard. There’s your answer.”

Others questioned whether there was a darker subtext. “They just want to hide how much the thing have [sic] shrunk – shrinkflation strikes again.”

In recent years Jaffa Cake fans have faced diminishing returns. Not only has the number in the box reduced but two years ago the “cakes” shrank in size from 5.5cm to 5cm across. The orange bump became smaller, too.

Pension Insurance Corporation Group Limited (“PICG”), ultimate parent company of Pension Insurance Corporation plc (“PIC”), the specialist insurer of UK defined benefit pension schemes, today announces that Athora Holding Limited (“Athora”) has agreed to acquire PICG for approximately £5.7 billion. Athora is a leading pan-European savings and retirement services group with €76 billion of assets under management and administration, on behalf of 2.8 million policyholders. 

The transaction means that for the first time in its 20-year history, PIC will be held by a single strategic owner. PIC will become the UK insurance business of Athora and continue operating under the PIC (and penguin) brand. Athora has existing insurance businesses in the Netherlands, Italy, Belgium and Germany. Athora is backed by permanent capital owners, including a strategic minority investment by Apollo Global Management and Athene Holding Limited, and long-term institutional investors such as a wholly owned subsidiary of the Abu Dhabi Investment Authority (“ADIA”).

The transaction creates a total Group with assets of over €130 billion, backing the pensions of more than three million savers and retirees across Europe. PIC will be 45% of Athora’s total assets under management and administration, and will be the largest and fastest growing business in the Group. 

PIC has a portfolio of £50.9 billion backing the pensions of 400,000 people. It has £30 billion invested in the UK. To date it has invested £13.8 billion in UK housing and infrastructure, which help provide the secure, inflation-linked cashflows which match its pension liabilities over future decades. PIC has so far paid more than £16 billion in pensions, with a 99% customer satisfaction rating.

The acquisition reinforces PIC’s strategy of providing very high customer service levels and increases its ability to invest in UK housing and infrastructure as Athora supports PIC through the next phase of its growth. This will allow PIC to provide its best pricing across a larger number of pension risk transfer deals.

PICG’s current shareholders are Reinet Fund S.C.A., F.I.S. (“Reinet”) which holds 49.5% of the issued shares, a wholly owned subsidiary of ADIA, with 18.4% of the issued shares, funds managed by CVC Capital Partners (“CVC”), with 17.4%, and funds managed by HPS Investment Partners with 10.2%, as well as employees and other shareholders, who hold c.4% of the issued shares. The transaction, which is subject to regulatory approval, is expected to close in early 2026.

Tracy Blackwell, CEO of PIC, said: “PIC has had an amazing growth story over the past two decades and is now one of Britain’s preeminent pension businesses. This success has been based on a simple purpose, which is to pay the pensions of our current and future policyholders. Athora’s investment is validation of what we have always believed: that PIC’s reputation, strategy, fortress balance sheet, purpose, and most importantly our people combine to make this a unique business in a huge and growing market. 

“With Athora backing us through our next phase of growth as their UK insurance business, we will be able to provide more options to the trustees of defined benefit pension schemes and invest more in UK housing and infrastructure. The pension risk transfer market is vital to the wellbeing of millions of UK pensioners and the allocation of tens of billions of pounds of investment into the UK’s economy. This acquisition and the potential for growth that it represents is the strongest possible recognition of the value and importance of the pension risk transfer market, the sector that PIC helped to create and continues to lead.

“Finally, I want to thank our exiting shareholders who have been absolutely brilliant in getting us to this point. I very much look to the next chapter in PIC’s story.”

Mike Wells, CEO of Athora, said: “We are delighted to have agreed this transaction. We have followed PIC’s progress for several years and been consistently impressed by the very high-quality business the PIC team has built. As our UK subsidiary, PIC will be the largest business within the Athora Group and we intend to invest in the business and its people to support that growth in the UK pension risk transfer market. We have great confidence in the long-term strengths of the UK: its retirement market, regulatory and policy framework, and economic prospects.”

Dillie Malherbe, Director: Reinet Investments Manager, said: “We have been invested in PICG since 2012, and have helped oversee a 900% increase in the size of the business since then, by size of financial investments. What has consistently impressed me about PIC is that, despite that amazing growth trajectory, it has maintained a relentless focus on outcomes for its policyholders. I want to thank Tracy, our fellow shareholders, and everyone at PIC for all their efforts over the past 13 years.”

Hamad Shahwan Aldhaheri, Executive Director of the Private Equities Department at ADIA, said: “As a shareholder in PICG since 2018, our investment supported the growth of the company as it strengthened its position as one of the leading players in the UK pension risk transfer market. Following this transaction, we will maintain exposure to the company via our existing shareholding in Athora, and believe that PIC has strong prospects for the future. We wish the company continued success as part of Athora.”

The general rules of the Mexican Social Security Institute came into effect on July 1, 2025, ensuring that individuals working for “digital platforms” receive social security benefits. This follows the reform of the Federal Labor Law (FLL) regarding digital platforms, amended in December 2024.

The key points of the general rules are as follows:

• Mexican Social Security Institute Registration: Companies providing digital platform services must register with the Mexican Social Security Institute those workers who earn at least the general monthly minimum wage. Currently, the general daily minimum wage is $278.00 pesos.
• Determination and Payment of Contributions: Platforms must calculate, withhold and pay employer-employee social security contributions, including those for sickness and maternity insurance, occupational risk, disability and life insurance, as well as for contributions to the National Workers’ Housing Fund Institute.
• Base Salary for Contributions: The calculation of contributions will be based on the worker’s net monthly income earned through the platform, excluding tips and other items not recognized by the FLL.
• Mexican Social Security Institute Digital Module: The authority will develop a specific digital module so that platforms can carry out registration, enrollment and payment of contributions digitally.
• No Obligation for Independent Workers: It is confirmed that independent workers who do not reach the established income threshold (the monthly minimum wage) are not required to be insured under this scheme, unless they choose to enroll voluntarily.
• Termination of Employment Relationship After 30 Days of Inactivity: It is confirmed that the employment relationship will be considered terminated if the worker ceases activity for 30 consecutive calendar days, and accordingly, the obligation to pay Mexican Social Security Institute contributions will cease.
• Pilot Program: These rules are part of the mandatory pilot program provided for in the reform, intended to validate the operational scheme before its definitive implementation to ensure it is functional and does not affect the Mexican Social Security Institute’s finances (for up to 180 days).
• No Employment Relationship: There will be no employment relationship when services are provided through digital platforms involving vehicle leasing or without subordination, provided legal requirements are met. In these cases, there will be no labor or social security obligations, except as stipulated in the FLL.

It is important to analyze the impact these new obligations may have for companies that operate or contract services through digital platforms, especially regarding costs, payroll administration, social security and legal compliance.

For additional guidance on implementing these requirements or assessing their implications for your organization, please contact the authors.

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Information contained in this alert is for the general education and knowledge of our readers. It is not designed to be, and should not be used as, the sole source of information when analyzing and resolving a legal problem, and it should not be substituted for legal advice, which relies on a specific factual analysis. Moreover, the laws of each jurisdiction are different and are constantly changing. This information is not intended to create, and receipt of it does not constitute, an attorney-client relationship. If you have specific questions regarding a particular fact situation, we urge you to consult the authors of this publication, your Holland & Knight representative or other competent legal counsel.

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The addition of ipilimumab (Yervoy) to nivolumab (Opdivo) not only led to a significant improvement in progression-free survival (PFS) over nivolumab alone, but it also resulted in better health-related quality of life (HRQOL) and reduced symptoms in patients with microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC), according to additional analyses from the phase 3 CheckMate 8HW trial (NCT04008030).¹

At the 2025 ESMO Gastrointestinal (GI) Cancers Congress, it was shared that of the 582 total patients treated with the doublet or with nivolumab alone on the trial, questionnaire completion rates ranged from 91% to 95% at baseline. Investigators leveraged the EORTC QLQ-C30, EORTC QLQ-CR29, and EQ-5D-3L instruments to examine mean changes from baseline vs week 21. Improvements in functioning and decreases in symptoms were observed for both treatment groups across all key functional domains and symptoms, with slightly greater improvements in the nivolumab/ipilimumab arm.

When they analyzed the mean change from baseline in global health status (GHS) scores, they found that in both treatment groups, GHS scores showed a trend for improvement starting at week 7. In the doublet arm, GHS scores remained at, or near, the minimally important change from baseline starting at week 21; the nivolumab-alone arm had slightly less improvement.

They also examined the mean change from baseline in fatigue scores. In both treatment groups, fatigue scores demonstrated a trend for improvement starting at week 7. In the doublet arm, fatigue scores exceeded the minimally important change from baseline starting at week 21 vs week 85 in the nivolumab-alone arm. Improvements in fatigue scores from baseline were numerically better in those who received the doublet vs those given the monotherapy starting at week 21; however, the analysis was not designed to formally compare the treatment arms.

When looking at mean change from baseline in ED-5D-3L visual analogue scores, which is a measure of patients’ self-reported health, the score demonstrated a trend for improvement starting at week 7 in both treatment groups. In the doublet arm, the visual analogue scores exceeded the minimally important change from baseline starting at week 21; for the monotherapy arm, the minimally important change from baseline was exceeded starting at week 61.

Lastly, they assessed mean change from baseline in EQ-5D-3L utility index scores. In both treatment groups, these scores indicated a trend for improvement starting at week 7. Those in both the nivolumab/ipilimumab and nivolumab-alone arms exceeded the minimally important change from baseline starting at week 29.

“The addition of nivolumab to ipilimumab significantly improved PFS compared [with] nivolumab immunotherapy while maintaining HRQOL,” Elena Elez MD, PhD, said in a presentation of the data. Elez is a medical oncology consultant at Vall d’Hebron University Hospital and senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain.

Checking Out CheckMate 8HW: Eligibility, Treatment, End Points

The randomized, multicenter, open-label, phase 3 study enrolled patients with histologically confirmed unresectable or mCRC who had MSI-H/dMMR status by local testing, had not been previously exposed to immunotherapy, and had an ECOG performance status of 0 or 1.

They were randomly assigned in a 2:2:1 fashion to receive 240 mg of nivolumab every 2 weeks for 6 doses followed by 480 mg of nivolumab every 4 weeks (n = 353); 240 mg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 480 mg of nivolumab every 4 weeks (n = 354); or investigator’s choice of chemotherapy in the form of mFOLFOX6 or FOLFIRI with or without bevacizumab (Avastin) or cetuximab (Erbitux; n = 132). Treatment continued until progressive disease, unacceptable toxicity, withdrawn consent, or the maximum treatment duration of 2 years.

Patients were stratified based on number of prior lines of treatment (0 vs 1 vs ≥2) and primary tumor location (right vs left). The trial had dual primary end points: PFS by blinded independent central review (BICR) for the doublet vs chemotherapy in the first-line setting and PFS by BICR for the doublet vs nivolumab alone across all lines—all in those with MSI-H/dMMR mCRC. Other end points included safety, PFS2, objective response rate by BICR, overall survival, and HRQOL.

What Came Before

Previous data indicated that nivolumab plus ipilimumab (n = 296) yielded to a statistically significant and clinically meaningful improvement in PFS vs nivolumab alone (n = 286) in those with centrally confirmed MSI-H/dMMR mCRC across all lines of therapy. The median PFS was not reached (95% CI, 53.8-not evaluable [NE]) with the doublet vs 39.3 months (95% CI, 22.1-NE) with nivolumab alone (HR, 0.62; 95% CI, 0.48-0.81; P = .0003).² The 12-, 24-, and 36-month PFS rates in the doublet arm were 76%, 71%, and 67%, respectively; in the monotherapy arm, these respective rates were 62%, 55%, and 51%.

Elez noted that the PFS benefit with the combination vs the nivolumab alone also proved to be consistent in all randomly assigned patients, at a median of 54.1 months vs 18.4 months, respectively (HR, 0.64; 95% CI, 0.52-0.79).¹

In April 2025, the FDA granted accelerated approval to nivolumab plus ipilimumab for the treatment of adult and pediatric patients at least 12 years of age with dMMR or MSI-H unresectable or mCRC based on CheckMate 8HW data.³ The combination was also cleared in the European Union and other countries for this indication.¹ Elez added that previously, first-line nivolumab plus ipilimumab improved HRQOL in key functioning scales and reduced symptoms compared with chemotherapy.

Breaking Down the Basics of the Current Analysis

For the analysis shared during the 2025 ESMO GI Cancers Congress, Elez shared HRQOL findings for nivolumab plus ipilimumab compared with nivolumab alone across all lines of treatment. The data cutoff was August 28, 2024, and the median follow-up was 47.0 months (range, 16.7-60.5).

These analyses included those with centrally confirmed MSI-H/dMMR mCRC who had received at least 1 dose of the combination or nivolumab monotherapy. They were evaluated with EORTC QLQ-C30, EORTC QLQ-CR29, and EQ-5D-3L questionnaires, which were answered at baseline, defined as before day 1 of cycle 1; day 1 cycle 2; day 1 cycle 3; then every other cycle thereafter, or every 8 weeks. “As a reminder, the C30 refers to [patients with] cancer, the CR29 is specifically for [patients with] CRC, and the EQ-5D-3L refers to all illness beyond patients with cancer,” Elez explained.

The questionnaires were scored per their scoring instructions, and data were summarized through descriptive analyses, which included mean scores and changes from baseline, standard deviation of the means, medians, interquartile range, and minimum and maximum values at each time point.

Disclosures: Elez disclosed serving in consulting or advisory roles for Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cureteq, Jannsen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Roche-Genentech, Sanofi, Seagen, Servier, and Takeda. Honoraria was received from Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cureteq, Janssen, Lilly, Medscape, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Roche-Genentech, Sanofi, Seagen, Servier, and Takeda. Research funding (institution) was provided by AbbVie, Amgen, Array BioPharma, AstraZeneca, Bayer, BeiGene, Biontech, BioNTech, Boehringer Ingelheim, Boehringer Ingelheim (Spain), Bristol Myers Squibb, Celgene, Daiichi Sankyo, Debiopharm Group, Gercor, HailoDx, Huchison MediPharma, Iovance Biotherapeutics, Janssen-Cilag, Janssen R&D, MedImmune, Menarini, Merck, Merck Sharp & Dohme, Merus NV, Mirati, Novartis, Nouscom, PharmaMar, Pfizer, PledPharma, RedX Pharma, Pierre Fabre, Roche-Genentech, Sanofi, Scandion Oncology, Seagen, Servier, Sotio, Taiho, and WntResearch. Travel or accommodation expenses were provided by Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cureteq, Janssen, Lilly, Medscape, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Roche-Genentech, Sanofi, Servier, Seagen, and Takeda. The study was funded by Bristol Myers Squibb.

References

1. Elez E, Andre T, Lonardi S, et al. Nivolumab plus ipilimumab vs nivolumab monotherapy for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: health-related quality of life analyses from CheckMate 8HW. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 1O.
2. Lonardi S, André T, Arnold D, et al. 2O Health-related quality of life (HRQoL) with first-line (1L) nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): CheckMate 8HW. Ann Oncol. 2024;35(suppl 1):S1-S2. doi:10.1016/j.annonc.2024.05.013
3. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. FDA. April 8, 2025. Accessed July 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-msi-h-or-dmmr-colorectal-cancer

Budget airline Ryanair is planning to increase its “personal bag” size by 20% as the EU brings in a new standard.

Passengers will be allowed to take an item such as a handbag or laptop bag measuring up to 40cm x 30cm x 20cm in the cabin without paying an extra fee. It should weigh less than 10kg, and fit “under the seat in front you.”

The new size represents a 20% increase in volume from the current maximum dimensions.

This will mean that Ryanair accepts free bags one third bigger than the new EU minimum size limit.

Ryanair said the new free bag size would come into effect in the coming weeks as its bag size measuring devices were adjusted to the new standard.

It’s current maximum bag size is 40cm x 25cm x 20cm, which already has a greater volume than the new European standard of 40cm x 30cm x 15cm.

Ryanair declined to say why it was giving passengers a larger carry-on bag allowance.

The size is still less generous than rival budget airline Easyjet, which allows a free underseat bag of 45cm x 36cm x 20cm (including wheels and handles) weighing up to 10kg.

Wizz Air allows one cabin bag as big as Ryanair’s new limits – 40cm x 30cm x 20cm, with the same weight limit of 10kg.

BA has a slightly smaller limit for an under-seat laptop bag or handbag of 40cm x 30cm x 15cm, but passengers are allowed to take a larger cabin bag as well free of charge, subject to a maximum weight of 23kg.

The EU has been working with airlines to agree a minimum free bag size, so that frequent travellers can purchase one piece of luggage and be confident it would be accepted by multiple airlines.

The rule applies to airlines based in the EU – which includes Easyjet, Ryanair and Wizz Air – but airlines are of course free to accept larger bags if they choose.

Confusion about the different minimum sizes has caused problems for passengers, who have sometimes been faced with unexpected extra fees when airlines said their bags didn’t match the specified dimensions.

Last month the transport committee of the European parliament voted to give passengers the right to an extra piece of free hand luggage weighing up to 7kg. The proposed rule would still have to be passed by the wider European parliament.

Passengers should confirm baggage rules with their airlines directly.

The addition of durvalumab (Imfinzi) to perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) did not lead to differences in overall health-related quality of life (QOL), patient function, or symptom burden vs placebo plus FLOT in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to an analysis of patient-reported outcomes (PROs) from the phase 3 MATTERHORN trial (NCT04592913).¹

Data presented at the 2025 ESMO Gastrointestinal Cancers Congress demonstrated that no clinically meaningful deterioration in global health score (GHS)/QOL, physical function, or role function was observed for durvalumab plus FLOT (n = 467) vs placebo plus FLOT (n = 459) at 3 months following the completion of treatment. Similarly, PROs were comparable between the 2 arms in terms of symptom burden, including dysphagia, eating restrictions, anxiety, dry mouth, taste, hair loss, body image, weight loss, fatigue, and appetite loss.

PROs recorded over the course of treatment showed that there was no clinically meaningful deterioration in GHS/QOL in either arm overall. Notably, clinically relevant deterioration in GHS/QOL—defined as a decrease of at least 10 points—occurred in both arms during cycles 4 and 5, but this improved to a decrease of less than 10 points by cycle 5 in both groups.

Additionally, there was no relevant difference in time to deterioration (TTD) in PROs between the 2 treatment groups. The median TTD for GHS/QOL was 13.86 months (95% CI, 11.24-19.98) in the durvalumab arm vs 13.60 months (95% CI, 10.68-16.46) in the placebo arm (HR, 0.90; 95% CI, 0.76-1.07). Regarding physical function, the median TTD was 13.70 months (95% CI, 10.94-17.84) and 11.93 months (95% CI, 9.26-15.38) for the durvalumab and placebo regimens, respectively (HR, 0.89; 95% CI, 0.75-1.05). For role function, the median TTD was 10.12 months (95% CI, 7.98-11.66) for those given durvalumab and 8.34 months (95% CI, 7.23-10.68) for those given placebo (HR, 0.90; 95% CI, 0.76-1.05).

“This [PRO] analysis supports the positive risk:benefit profile of perioperative durvalumab [plus] FLOT in patients with localized gastric and GEJ adenocarcinoma,” lead study author Salah-Eddin Al-Batran, MD, of Krankenhaus Nordwest, University Cancer Center (UCT) Frankfurt and Frankfurt Institute of Clinical Cancer Research in Germany, said in a presentation of the data.

Revisiting Efficacy Data From MATTERHORN

Data presented at the 2025 ASCO Annual Meeting showed MATTERHORN met its primary end point, with patients treated with durvalumab plus FLOT achieving a statistically significant improvement in event-free survival (EFS) compared with those treated with placebo plus FLOT (HR, 0.71; 95% CI, 0.58-0.86; P < .001).² The median EFS was not reached (NR; 95% CI, 40.7-NR) for the durvalumab arm vs 32.8 months (95% CI, 27.9-NR) in the placebo arm.

The median overall survival (OS) was NR (95% CI, NR-NR) for patients in the durvalumab group vs 47.2 months (95% CI, 45.1-NR) for those in the placebo arm (HR, 0.78; 95% CI, 0.62-0.97; P = .025). Although this difference was not statistically significant, Al-Batran noted that data from the final OS analysis are pending.¹

MATTERHORN Background and PRO Analysis

The global, randomized, double-blind, placebo-controlled study enrolled patients with stage II to IVA gastric or GEJ adenocarcinoma who had no evidence of metastases, received no prior therapy, and had an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive neoadjuvant FLOT in combination with durvalumab or placebo, followed by surgery and adjuvant FLOT plus durvalumab or placebo, then 10 cycles of durvalumab or placebo monotherapy. In both the neoadjuvant and adjuvant combination portions, FLOT was given for 4 doses both before and after surgery, and durvalumab or placebo were given for 2 doses both before and after surgery.

Stratification factors included geographic region (Asia vs non-Asia), clinical lymph node status (positive vs negative), and PD-L1 expression (tumor area proportion [TAP] score <1% vs TAP ≥1%).

Along with the EFS primary end point, key secondary end points comprised OS and pathological complete response rate. Secondary PRO end points included TTD and change from baseline in function and symptoms.

The median age at baseline was 62 years (range, 26-84) in the durvalumab arm and 63 years (range, 28-83) in the placebo arm. Most patients in both arms were male (durvalumab, 69%; placebo, 75%), not from Asia (81%; 81%), had an ECOG performance status of 0 (71%; 77%), had gastric adenocarcinoma (68%; 67%), had non-T4 disease (75%; 75%), had node-positive disease (69%; 70%), had a PD-L1 TAP of at least 1% (90%; 90%), had an intestinal histology (52%; 50%), and did not have microsatellite instability–high disease (64%; 65%).

Baseline PROs were similar between the durvalumab and placebo arms in terms of function as evaluated by the EORTC QLQ-C30 questionnaire and function per the EORTC QLQ-STO22 + IL38 questionnaire. “We can also see that patients were mildly symptomatic compared [with patients with] metastatic [disease], reflecting the ECOG performance status for patients in this study,” Al-Batran explained.

Furthermore, compliance rates for PROs were high in both arms over the course of the study. After utilizing the EORTC QLQ-C30 and EORTC QLQ-STO22 + IL38 questionnaires at baseline, PROs were recorded with these forms from cycles 2 through 14. Compliance rates for both questionnaires never dipped below 76.3% in either arm at any assessment point during treatment, and the vast majority of cycles had compliance rates above 80% in both groups.

Safety Data

Safety findings, which were also presented at the ASCO Annual Meeting in June, showed that any-grade adverse effects (AEs) were reported in 99% of patients in both arms. AEs possibly related to study treatment occurred in 95% of patients in both groups. Grade 3/4 AEs were observed in 72% of patients in the durvalumab arm vs 71% of patients in the placebo group, and the rates of grade 3/4 AEs possibly related to treatment were 60% and 59%, respectively. Serious AEs were reported at rates of 48% for the durvalumab regimen vs 44% for the placebo regimen.

AEs led to discontinuation of any study treatment in 30% of patients in the durvalumab arm vs 23% of those in the control arm. Durvalumab was discontinued in 10% of patients due to AEs, whereas 6% of patients discontinued placebo. AEs led to FLOT discontinuation in 25% and 20% of patients, respectively. Fatal AEs occurred in 5% of patients in the durvalumab arm vs 4% of patients in the placebo arm. The rates of fatal AEs possibly related to durvalumab or placebo were 1% and less than 1%, respectively. AEs leading to death possibly related to FLOT occurred in 1% and less than 1% of patients, respectively.

Any-grade immune-mediated AEs (irAEs) occurred in 23% of patients in the durvalumab group vs 7% of those in the placebo arm. Grade 3/4 irAEs were reported in 7% and 4% of patients, respectively. AEs prevented surgery in 1% of patients in the durvalumab group vs less than 1% of patients in the placebo group. Surgery was delayed due to AEs in 2% and 3% of patients, respectively.

Disclosures: Al-Batran reported serving in advisory roles for AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly Germany, and Merck Sharp & Dohme; receiving funding from AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eli Lilly Germany, Eurozyto, Federal Ministry of Education and Research, German Cancer Aid, German Research Foundation, Immutep, Ipsen, Merck Sharp & Dohme, Roche, Sanofi, and Vifor Pharma; having an ownership interest in Frankfurter Institut für Klinische Krebsforschung; and serving in a speakers’ bureau for AlO GmbH, Bristol Myers Squibb, Eli Lilly Germany, and MCI Group.

References

1. Al-Batran S-E, Wainberg ZA, Muro K, et al. Event-free survival (EFS) and patient-reported outcomes (PROs) in MATTERHORN: A randomised, phase III study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Presented at: 2025 ESMO Gastrointestinal Cancer Congress; July 2-5, 2025; Barcelona, Spain. Abstract LBA4.
2. Janjigian Y, Al-Batran S-E, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5