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Michiel van der Heijden, MD, PhD, medical oncologist at the Netherlands Cancer Institute in Amsterdam, presented the findings at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.

At last year’s ESMO Congress in Barcelona, Spain, Thomas B. Powles, MBBS, MRCP, MD, presented findings from NIAGARA. The patient population consisted of adults with cisplatin-eligible MIBC (cT2-T4aN0/1M0), urothelial cancer or urothelial cancer with divergent differentiation or histologic subtypes, evaluated and confirmed for radical cystectomy, and with creatine clearance of 40 mL/min or lower. Patient were randomly assigned 1:1 to either the durvalumab arm or the comparator arm. Patients in the durvalumab arm received neoadjuvant durvalumab, 1500 mg intravenously every 3 weeks and gemcitabine plus cisplatin for 4 cycles followed by radical cystectomy and 8 cycles of adjuvant durvalumab. Patients in the comparator arm received 4 cycles of gemcitabine plus cisplatin for 4 cycles followed by radical cystectomy. The 2 primary end points were event-free survival (EFS) and pathological complete response. Regarding EFS, there was a significant reduction in risk (HR=0.68, 95% CI, 0.56-0.82). Median follow-up was 42.3 months (range 0.03-61.3 months).^2,3

Data from NIAGARA supported the FDA’s approval of neoadjuvant durvalumab in combination with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy following radical cystectomy, for adult patients with muscle invasive bladder cancer.⁴

At ESMO 2025, van der Heijden presented HRQOL outcomes from the NIAGARA study. In NIAGARA, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EQ-5D-5L were assessed via electronic device at baseline and every 4 weeks until disease progression. van der Heijden explained that the EORTC QLQ-C30 measures global health scale (GHS)/QoL as well as functional and symptom subscales. GHS/QoL and Physical, Fatigue, and Pain were included in NIAGARA as prespecified priority subscales, with a 10-point change in score compared with baseline being deemed clinically meaningful.

The EQ-5D-5L visual analogue scale is constructed for patients to rate their current overall health; for NIAGARA, the investigators reported visual analogue scale change from baseline.

A total of 439 (82.4%) of patients in the durvalumab arm completed the baseline EORTC QLQ-C30 assessment vs 450 (84.9%) patients in the comparator arm. In addition, 416 (78.0%) patients in the durvalumab arm completed the baseline and at least 1 postbaseline assessment vs 410 (77.4%) of patients in the comparator arm. The compliance rate range from baseline to adjuvant week 29 was 50.9%-82.4% in the durvalumab arm vs 44.3%-84.9% in the comparator arm.

For the EQ-5D-5L, 417 (78.2%) patients completed the baseline assessment vs 430 (81.1%) patients in the comparator arm. Further, 391 (73.4%) patients in the durvalumab arm completed the baseline and at least 1 postbaseline assessment vs 380 (71.7%) patients in the comparator arm. The compliance rate range from baseline to adjuvant week 29 was 49.9%-78.2% in the durvalumab arm vs 43.2%-81.1% in the comparator arm.

For GHS/QoL, van der Heijden reported that that the difference between arms for overall mean change from baseline (CFB) was 1.6 (95% CI, –0.44 to 3.69), and with the Physical Functioning subscale, the difference between arms for overall CFB was 1.2 (95% CI, –0.80 to 3.17). For the Fatigue subscale, the difference between arms for overall CFB was –0.9 (95% CI, –3.25 to 1.52), and for the Pain subscale, the difference between arms for overall CFB was –2.1 (95% CI, –4.44 to 0.16).

The EQ-5D-5L visual analogue scale “also did not show any difference between the treatment arms,” according to van der Heijden.

“Overall, the addition of perioperative durvalumab to neoadjuvant chemotherapy significantly improved event-free survival and overall survival without adversely affecting patient-reported outcomes,” van der Heijden said in his concluding remarks.

References

1. van der Heijden M, Powles TB, Galsky MD, et al. Health-related quality of life (HRQOL) outcomes from the NIAGARA trial of perioperative durvalumab (D) plus neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC). Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 3069MO.
2. Powles TB, van der Heijden MS, Galsky MD, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA5.
3. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. Published online September 15, 2024. Accessed October 17, 2025. https://www.nejm.org/doi/abs/10.1056/NEJMoa2408154
4. FDA approves durvalumab for muscle invasive bladder cancer. News release. US Food & Drug Administration. Published online March 28, 2025. Accessed October 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer
5. IMFINZI (durvalumab) approved in the US as first and only perioperative immunotherapy for patients with muscle-invasive bladder cancer. News release. AstraZeneca. Published online March 31, 2025. Accessed October 17, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-approved-in-the-US-as-first-and-only-perioperative-immunotherapy-for-patients-with-muscle-invasive-bladder-cancer.html

Durvalumab (Imfinzi) in combination with chemotherapy produced outcomes consistent with prior studies in patients with advanced pleural mesothelioma, demonstrating favorable overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) trends, according to findings from the phase 3 DREAM3R trial (NCT04334759) presented at the 2025 ESMO Congress. However, challenges with patient accrual and evolving standard-of-care practices limited the conclusiveness of the results.

Data were presented at the 2025 European Society for Medical Oncology (ESMO) Congress. Durvalumab and chemotherapy yielded a median OS of 21 months (95% CI, 18–27) vs 18 months for chemotherapy alone (95% CI, 14–30) for a HR of 0.92 (95% CI, 0.63–1.36; stratified log-rank P =.9). Median PFS were 8 months (95% CI, 8–10) with the combination vs 7 months (95% CI, 6–8) with chemotherapy alone (HR, 0.70; 95% CI, 0.5–0.98; P =.20). ORRs were 58% and 35%, respectively (P =.005).

The safety profiles of chemotherapy with or without durvalumab were consistent with the known profiles of the agents. Fatigue, nausea, and anemia were the most common adverse events (AEs) in both arms.

What Was the Rationale and Design of the DREAM3R Trial?

Durvalumab was assessed in the phase 2 DREAM (ACTRN12616001170415) and PrE0505 (NCT02899195). In these studies, durvalumab showed promising activity in combination with pemetrexed and either cisplatin or carboplatin chemotherapy.

The phase 3 DREAM3R study randomized patients 2:1 to receive durvalumab 1500 mg every 3 weeks plus chemotherapy every 3 weeks for 4 to 6 cycles, followed by durvalumab maintenance 1500 mg every 4 weeks until progressive disease or unacceptable toxicity, or chemotherapy every 3 weeks for 4 to 6 cycles. Accrual started in February 2021.

However, the results of the CheckMate 743 study (NCT02899299) published in 2021 showed that nivolumab (Opdivo) and ipilimumab (Yervoy) significantly improved OS vs chemotherapy.² As the standard of care in pleural mesothelioma had changed, the study design changed to incorporate a nivolumab/ipilimumab arm, and randomization changed to 1:1 durvalumab/chemotherapy or physician’s choice of nivolumab/ipilimumab or chemotherapy.¹ At this ESMO Congress, only data from the durvalumab and chemotherapy cohorts were presented.

A total of 114 patients received chemotherapy and durvalumab and 60 patients received chemotherapy alone. The study’s primary end point was OS. Secondary end points included PFS, ORR, and AEs.

What Are the Next Steps?

During her presentation, Anna Nowak, MD, deputy vice chancellor at the University of Western Australia, noted that, while DREAM3R was a well-designed study, due to the early stopping of DREAM3R, it is unlikely that the study question will ever be answered.

“The key limitation is that slow accrual led to early stopping, and this slow accrual was no doubt, an artifact, partly of the global pandemic, but also then of a change of clinical practice as a result of the of the CheckMate 743 study and subsequent regulatory approval and standard clinical care use,” Nowak explained. “These design modifications add complexity to the interpretation of this clinical trial, and of course, chemotherapy alone would no longer be considered standard of care.”

Nowak did note that the high objective tumor response and control observed with chemotherapy and durvalumab raised the potential for future testing in the neoadjuvant setting. Additionally, correlative biomarkers that were collected from DREAM3R are also under ongoing analysis.

Further, Nowak emphasized the importance of timely activation of randomized phase 3 trials after positive phase 2 trials “is critically important to seize the window of opportunity for accrual and provide reliable answers.” Nowak added that, “the reasons for the delay in starting this trial were multifactorial.”

Disclosures: Nowak declared participation on AstraZeneca Data Safety Monitoring Board, board membership on Cancer Council Western Australia, position on Cancer Australia Advisory Council, and president-elect of the International Mesothelioma Interest Group.

References

1. Nowak A. Primary results of DREAM3R: DuRvalumab (MEDI4736) with chemotherapy as first line treatment in advanced pleural Mesothelioma – A phase 3 Randomised trial. Presented at: 2025 ESMO Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA104.

2. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8. Epub 2021 Jan 21.