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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

Meta CEO Mark Zuckerberg is shaking up the artificial intelligence domain with a massive, unprecedented recruitment drive that is not only targeting OpenAI’s top talent but also making it even harder for the US government to build its own tech bench.

Zuckerberg is offering mind-boggling compensation packages, sometimes exceeding $100 million in the first year alone to lure leading AI researchers from OpenAI and other companies. Over four years, total payouts could soar to $300 million, as reported by WIRED. These are not just high salaries, they rival the kind of money usually reserved for star athletes or major start-up valuations.

The campaign culminated this week with Zuckerberg unveiling Meta Superintelligence Labs (MSL), his new elite AI division. The Meta founder has personally courted potential hires at his residences in Palo Alto and Lake Tahoe. His most high-profile recruit so far is Alex Wang, co-founder of Scale AI, who will serve as Meta’s Chief AI Officer. Former GitHub CEO Nat Friedman will lead product and applied AI development. Eleven other top-tier hires were listed in an internal memo.

Zuckerberg’s all-out raid is dramatically inflating AI compensation and intensifying a talent war already underway in Silicon Valley. The ripple effect is particularly damaging for the U.S. government, which was already struggling to compete for AI expertise. With tens of millions now easily attainable in private industry, public service becomes a much harder sell.

Meanwhile, Chinese tech firms are quickly gaining ground, supported by their government’s ability to direct top talent into state projects. A recent Wall Street Journal report warned that China’s AI models from companies like DeepSeek and Alibaba—are rapidly gaining traction across Asia, Europe, and Africa.

Backdrop and implications

Zuckerberg’s hiring spree is part of a larger strategic pivot, reminiscent of his earlier move to shift Facebook’s focus to mobile. Then, he bought Instagram and WhatsApp to catch up. Now, instead of acquiring companies, he’s betting on individuals.

It’s a bold move—but not without risk. Meta has spent heavily developing its large language model, Llama, to catch up with ChatGPT, Claude, and Gemini. But The Wall Street Journal notes that Meta’s track record in generative AI has made some recruits hesitant.

Still, Zuckerberg sees the opportunity clearly. OpenAI has projected massive growth—$10 billion in annual revenue already, with targets of $125 billion by 2029 and $174 billion by 2030. Anthropic, another OpenAI spinoff, is on a $4 billion annual revenue pace. For Meta, the payoff of dominating this sector could be trillions in long-term gains.

Altman’s response

OpenAI CEO Sam Altman acknowledged the aggressive poaching attempt, telling employees that Meta did manage to hire “a few great people” but largely missed out on OpenAI’s top talent. In a Slack message, he commented, “Missionaries will beat mercenaries,” stressing that OpenAI’s strength lies in its mission-driven culture.

He also pointed out on a recent podcast that OpenAI’s financial model rewards success with strong long-term incentives, aligning innovation with economic gain.

The broader concern

This highly public bidding war reflects an underlying AI arms race that’s now impacting national interests. For government agencies, the challenge is existential. They’re increasingly priced out of a market where the world’s biggest corporations treat top researchers like venture-backed unicorns. And without major reforms or incentives, Uncle Sam may be left watching from the side-lines.