Sabrina Serani

In phase 3 DREAM3R, first-line Imfinzi plus chemotherapy showed survival and response benefits in advanced mesothelioma, but results were inconclusive.

In the phase 3 DREAM3R study, first-line treatment with Imfinzi (durvalumab) plus chemotherapy demonstrated consistent improvements in overall survival, progression-free survival, and objective response rates among patients with advanced pleural mesothelioma, echoing findings from earlier phase 2 trials. Despite these positive trends, slow patient enrollment and evolving standards of care led to inconclusive results, leaving several key questions unresolved.

Data from the trial were presented at the 

. In patients treated with Imfinzi and chemotherapy, the median overall survival was 21 months compared with 18 months for patients receiving chemotherapy alone. Median progression-free survival was 8 months with the combination versus 7 months with chemotherapy alone. The objective response rate, which measures the proportion of patients who experienced tumor shrinkage, was 58% with Imfinzi plus chemotherapy versus 35% with chemotherapy alone.

The safety profile of chemotherapy, with or without Imfinzi, was consistent with the known effects of these treatments. Fatigue, nausea, and anemia were the most commonly reported side effects in both treatment groups, consistent with what has been seen in previous studies of these therapies.

Rationale and Design of the DREAM3R Trial

Imfinzi was previously evaluated in the phase 2 DREAM and PrE0505 trials, in which it demonstrated promising activity when combined with pemetrexed and either cisplatin or carboplatin chemotherapy. The phase 3 DREAM3R study enrolled patients with advanced pleural mesothelioma and patient enrollment began in February 2021.

Overall survival (OS): The length of time patients remain alive after starting treatment.

Progression-free survival (PFS): The length of time patients live without the cancer getting worse.

Objective response rate (ORR): The percentage of patients whose tumors shrink or disappear after treatment.

Neoadjuvant setting: Treatment given before the main therapy (such as surgery) to shrink a tumor.

Randomized trial: A study in which patients are assigned by chance to different treatment groups to compare outcomes.

The trial design was influenced by findings from the CheckMate 743 study in 2021, which demonstrated that nivolumab (Opdivo) combined with ipilimumab (Yervoy) significantly improved overall survival compared with chemotherapy alone. This change in standard treatment led to modifications in the DREAM3R trial, including the addition of a nivolumab/ipilimumab arm and adjusting the randomization to 1:1 for Imfinzi plus chemotherapy versus physician’s choice of nivolumab/ipilimumab or chemotherapy. At the 2025 ESMO Congress, only data from the Imfinzi and chemotherapy cohorts were presented.

A total of 114 patients received chemotherapy with Imfinzi, while 60 patients received chemotherapy alone. The trial’s primary end point was overall survival. Secondary end points included progression-free survival, objective response rate, and side effects.

Next Steps and Implications After the DREAM3R Study

Dr. Anna Nowak, deputy vice chancellor at the University of Western Australia, noted that although DREAM3R was a well-designed study, early trial termination due to slow enrollment makes it unlikely that the primary study question will ever be definitively answered. She explained that slow patient enrollment was influenced by the global pandemic and by changes in clinical practice following the CheckMate 743 study, which complicates interpretation of the findings. Chemotherapy alone is no longer considered standard treatment.

Despite this, Nowak emphasized that the high tumor response and disease control observed with Imfinzi plus chemotherapy suggest potential for future testing in the neoadjuvant setting, which is treatment given before surgery. Correlative biomarker analyses from DREAM3R are ongoing and may provide insights into which patients are most likely to benefit. She highlighted the importance of initiating randomized phase 3 trials promptly after positive phase 2 results to maximize enrollment and generate reliable evidence, noting that delays in starting the trial were due to multiple factors.

Overall, the DREAM3R trial provides valuable insights into the potential role of Imfinzi in combination with chemotherapy for advanced pleural mesothelioma, even though the study’s early termination limits definitive conclusions. The observed improvements in survival outcomes, tumor response, and disease control highlight the promise of this approach, particularly for patients who may benefit from earlier or neoadjuvant therapy. Ongoing analyses of correlative biomarkers and patient subgroups may further refine understanding of which patients are most likely to respond.

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

"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial," by Paul Baas. et al. 

For more news on cancer updates, research and education,

don’t forget to subscribe to CURE®’s newsletters here.

Articles

The phase 3 DREAM3R study evaluated the efficacy of Imfinzi (durvalumab) combined with chemotherapy in treating advanced pleural mesothelioma. Results showed improved overall survival, progression-free survival, and objective response rates compared to chemotherapy alone. However, slow patient enrollment and evolving treatment standards led to inconclusive results. The trial's early termination limits definitive conclusions, but the combination therapy's potential in neoadjuvant settings remains promising. Ongoing biomarker analyses may identify patients who benefit most, emphasizing the need for timely phase 3 trials following positive phase 2 outcomes.

Imfinzi With Chemo Produces Inconclusive Outcomes in Phase 3 Mesothelioma Study

Adding Imfinzi to Bacillus Calmette-Guérin therapy improved disease-free survival for patients with high-risk, non-muscle invasive bladder cancer.

Adding Imfinzi (durvalumab) to Bacillus Calmette-Guérin (BCG) therapy helped patients with high-risk, non-muscle invasive bladder cancer live longer without their cancer returning compared with BCG alone, according to results from a phase 3 study presented at the 2025 ESMO Congress.

The findings were presented by Dr. Maria De Santis, associate professor at the University of Warwick Medical School in Coventry, England, and simultaneously published in The Lancet.

The open-label, randomized study included 1,018 patients who were assigned in 3 cohorts: 339 received 1 year of Imfinzi with BCG induction and maintenance therapy, 339 received one year of Imfinzi with BCG induction only, and 340 received BCG induction and maintenance therapy alone.

The primary end point of DFS was achieved, with a 32% reduction in risk of a DFS event with the addition of Imfinzi to BCG induction and maintenance. Early and sustained DFS benefit with Imfinzi was observed starting as early as four months. The median follow-up was 60.7 months.

However, the difference in DFS for Imfinzi plus BCG induction only versus BCG induction and maintenance was not statistically significant.

While overall survival (OS) data were immature, there was no detriment to OS with the addition of Imfinzi to BCG induction and maintenance therapy.

Disease-free survival (DFS): time after treatment during which a patient lives without any signs or symptoms of cancer returning.

Overall survival (OS): time from treatment start or diagnosis until death from any cause.

The addition of Imfinzi to BCG induction and maintenance therapy had no major impact on patient-reported quality of life, one of the secondary end points of the trial.

Regarding safety, another key secondary end point, results showed that the Imfinzi/BCG regimen was tolerable and manageable with no unexpected side effects, and there were no deaths possibly related to the study treatment. Grade 3 (severe) or 4 (life-threatening) side effects possibly related to any treatment occurred in 21% of the Imfinzi/BCG induction and maintenance arm, 15% of the Imfinzi/BCG induction arm, and 4% of the BCG induction and maintenance arm.

The most frequently reported any-grade side effects in the Imfinzi/BCG induction and maintenance and BCG-only arms included dysuria (37% versus 36%, respectively), hematuria (32% versus 30%), pollakiuria (26% versus 25%), urinary tract infection (21% versus 18%), cystitis (19% versus 19%), and pyrexia (16% versus 20%).

“Overall, these events were consistent with what we expected for Imfinzi and BCG therapy with dysuria, hematuria, and pollakiuria being the three most commonly reported in both arms,” said De Santis during the presentation.

Most patients were male, and the median age was 68. Approximately 64% of patients had papillary disease only. Patients also had high-risk tumors, defined as being either T1, high grade, carcinoma in situ, or multiple and recurrent and large.

Patients received a median of six BCG induction instillations and 14 BCG maintenance instillations, with a maximum of 15 in both arms. More than half of patients received BCG for 18 months.

“In conclusion, these results support one year of Imfinzi with BCG induction and maintenance therapy as a potential new treatment in BCG-naive, high-risk NMIBC,” De Santis said during the presentation.

According to the National Cancer Institute, NMIBC refers to bladder cancers that have not grown into the muscle layer of the bladder wall. These cancers are confined to the inner lining (urothelium) or the connective tissue just beneath it. NMIBC includes stage 0 and stage 1 disease, meaning the tumor is limited to the surface or shallow layers of the bladder and has not invaded the deeper muscular wall.

“Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer” by Dr. Maria De Santis, et al., The Lancet.

The integration of Imfinzi (durvalumab) with BCG therapy in high-risk, non-muscle invasive bladder cancer (NMIBC) patients demonstrated a significant improvement in disease-free survival (DFS) compared to BCG alone, as per a phase 3 study. The study involved 1,018 patients and showed a 32% reduction in DFS events with Imfinzi addition. While overall survival data remain immature, no adverse impact on survival was noted. The treatment was well-tolerated, with manageable side effects, and no significant quality of life detriment was observed.

Imfinzi Plus BCG Improves Disease-Free Survival in High-Risk NMIBC

Combining Tecentriq with BCG therapy did not lead to better outcomes compared with BCG alone: © stock.adobe.com.

Combining Tecentriq (atezolizumab) with Bacillus Calmette-Guérin (BCG) therapy did not lead to better outcomes compared with BCG alone for patients with high-risk, non–muscle-invasive bladder cancer (NMIBC) who had not previously received BCG treatment. These findings, shared at the 2025 European Society for Medical Oncology (ESMO) Congress, showed that the addition of Tecentriq did not significantly improve the time patients lived without their cancer returning or worsening.

The findings, presented by Dr. Morgan Roupret, professor of urology at Sorbonne University in Paris, France, and simultaneously published in the 

, reported 73 events of 262 patients in the experimental combination arm versus 72 of 255 patients in the single-agent BCG arm. Events were defined as high-grade or low-grade NMIBC relapse, persistence of carcinoma in situ (CIS) after 6 months, progression of disease, appearance of upper tract urothelial carcinoma, or death of any cause.

“You don’t have to be a statistician to see the [Kaplan-Meier] curves are very close to one another,” Roupret said during the presentation.

Regarding the secondary end point of high-grade recurrence-free survival (RFS), defined as reappearance of high-grade NMIBC or death of any cause, there was also no improvement in the experimental arm. Data were not yet mature for an analysis of overall survival (OS), but there was no impact on the median survival with the addition of Tecentriq.

Side Effects Associated With Tecentriq and BCG Combination

Any-grade treatment-related side effects were reported in 94% (240 patients) and 76% (189 patients) of patients in the experimental and control arms, respectively. Grade 3 or higher and serious side effects occurred in 23% (58 patients) of those receiving Tecentriq and 9% (22 patients) of those receiving BCG only, and in 24% (60 patients) and 8% (21 patients) of patients, respectively.

Side effects leading to dose interruption occurred in 18% (47 patients) of the experimental arm versus 8% (9 patients) of the control arm. Treatment withdrawal due to side effects occurred in 29% (73 patients) and 9% (22 patients) of patients, respectively. In the experimental arm, 13% (32 patients) withdrew from BCG only, 16% (41 patients) withdrew from Tecentriq only, and 3% (8 patients) withdrew from both.

“Side effects such as rash and pruritus were common and consistent with previously published data. There was no particular surprise,” Roupret said.

How the ALBAN Trial Evaluated Tecentriq Plus BCG in High-Risk Bladder Cancer

The ALBAN study enrolled 517 patients who were BCG-naive with high-risk NMIBC after first- and second-look transurethral resection of bladder tumor (TURBT). High risk was defined as the presence of any high-grade or grade 3 Ta or T1 tumors and/or CIS. Patients were also required to have no metastatic disease in the pelvis, abdomen, or chest and an ECOG performance status of 0 to 2.

Patients were randomized 1:1 to receive BCG once a week for 6 weeks during the induction phase and once a week for 3 weeks at 3, 6, and 12 months during the maintenance phase, with or without Tecentriq, which was administered at 1200 mg intravenously every 3 weeks for up to 1 year.

The primary end point was EFS, and key secondary end points included high-grade RFS, progression-free survival, OS, duration of response, safety, and quality of life.

Understanding the ALBAN Study Population in High-Risk NMIBC

Patient characteristics were balanced between the treatment arms. The median age was 68 years in the combination arm versus 67 years in the control arm. Male patients comprised 84% (221 patients) of the experimental arm and 87% (221 patients) of the control arm.

Roupret noted that the only notable discrepancy between arms was smoking history. In the experimental arm, 66% (173 patients) identified as former smokers and 19% (50 patients) as current smokers. In the control arm, 62% (157 patients) were former smokers and 15% (38 patients) were current smokers.

What’s Next for NMIBC Treatment After the ALBAN Trial?

Roupret concluded that future research will focus on biomarker-driven patient selection based on integrated molecular and spatial immune profiling. He also emphasized the need to optimize the timing, duration, and delivery route of checkpoint inhibitors in NMIBC.

"ALBAN: A phase 3, randomized, open-label, international study of intravenous (IV) atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) vs BCG alone in BCG-naïve high-risk, non-muscle-invasive bladder cancer (NMIBC)," by Dr. Morgan Roupret. Presented at: ESMO 2025 Congress; Oct. 17–20, 2025; Berlin, Germany. Abstract LBA107.

"ALBAN (GETUG-AFU 27): A phase 3, randomized, open-label, international trial of intravenous atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) versus BCG alone in BCG-naïve high-risk, non-muscle invasive bladder cancer (NMIBC)," by Dr. Morgan Roupret. 

The combination of Tecentriq (atezolizumab) with Bacillus Calmette-Guérin (BCG) therapy did not improve outcomes for high-risk, non–muscle-invasive bladder cancer (NMIBC) patients compared to BCG alone. The ALBAN trial, presented at the 2025 ESMO Congress, showed no significant difference in event-free survival or high-grade recurrence-free survival between the two groups. Side effects were more prevalent in the combination arm, leading to higher rates of treatment withdrawal. Future research will focus on biomarker-driven patient selection and optimizing checkpoint inhibitor use in NMIBC.

The addition of Tecentriq to BCG therapy did not significantly improve outcomes for patients with non–muscle-invasive bladder versus BCG alone.

Tecentriq Plus BCG Does Not Improve Outcomes in Some With Bladder Cancer

Using a 14-gene test to guide chemotherapy significantly improved disease-free survival in patients with early nonsquamous lung cancer.

Among patients with stage 1a to 2a nonsquamous non–small cell lung cancer (NSCLC) identified as high risk by a 14-gene molecular assay who received adjuvant chemotherapy, the interim analysis of the international AIM-HIGH trial revealed a substantial improvement in disease-free survival (DFS) at 24 months, according to data presented at the 2025 ASCO Annual Meeting.

At 24 months, 96% of patients in the chemotherapy arm were alive without disease progression compared with 79% in the observation arm.

A similar improvement in DFS was observed in patients with stage 1a disease. In the chemotherapy arm, 98% of patients were alive without disease progression versus 78% in the observation arm.

"This is the first prospective randomized trial to show improvement in disease-free survival with a molecular risk discriminator in stage 1a through 2a nonsquamous non–small cell lung cancer,” Dr. David Spigel, said during the presentation. “Interim analysis was designed to detect a large discrepancy in outcomes between treated and untreated patients."

Disease-free survival (DFS): time a patient lives without signs of cancer after treatment.

Adjuvant chemotherapy: additional treatment given after surgery to lower the risk of cancer returning.

RiskReveal: a 14-gene test that evaluates lung cancer tumors to predict risk of early recurrence.

ECOG performance status: scale used to assess a patient’s ability to perform daily activities.

Spigel, chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, who presented the findings, highlighted the need for improved outcomes in early-stage NSCLC, noting that the 5-year DFS for even stage 1a disease remains under 65%, contributing to over 100,000 deaths worldwide. While adjuvant therapy is common in later stages, it is not typically recommended for stage 1a and often deferred in stages 1b and 2a.

“RiskReveal is a 14-gene lung cancer assay that examines the gene expression profile for nonsquamous non–small cell lung cancer and is used to identify patients at high risk of early disease. This assay has been prospectively validated in over 1400 patients with nonsquamous non–small cell lung cancer. Identifying patients who are at highest risk of recurrence is a priority in the treatment of non–small cell lung cancer,” Spigel explained.

The AIM-HIGH trial enrolled patients aged 18 years and older with completely resected stage 1a, 1b or 2a nonsquamous NSCLC. Following surgery, tumor tissue was analyzed using a commercially available 14-gene prognostic assay to identify patients at high or intermediate risk of early recurrence. Patients identified as low risk were not included in the study.

The trial randomized high-risk patients to either observation (the standard of care) or four cycles of platinum-based doublet chemotherapy per local standards. Immunotherapy and tyrosine kinase inhibitors were permitted at the investigator's discretion for appropriate patients.

The primary end point of the study was DFS, with routine CT scans and surveillance conducted for 5 years or until recurrence or death.

The interim analysis, which led to early stopping of the trial by the independent data safety monitoring board due to the significant difference observed, included 89 patients in the adjuvant chemotherapy arm and 111 patients in the control arm. Baseline characteristics, including gender, smoking history (predominantly former or current smokers), ECOG performance status (0 or 1), and stage of cancer (1a, 1b, 2a), were well balanced between the two arms.

Specifically, the median age of patients in the adjuvant chemotherapy arm was 63 years versus 66 in the observation arm, 47% of patients in both arms were female, 90% and 86% had a history of smoking, 67% and 65% had an ECOG performance status of 0, 31% and 34% had an ECOG performance status of 1, and 1% in each arm had an unknown ECOG performance status, respectively. A total of 97% of patients in the adjuvant chemotherapy arm had a histology of adenocarcinoma versus 93% in the control arm, and most patients had stage 1b disease (39% versus 41%).

The types of resections (primarily lobectomy) and the choice of adjuvant chemotherapy regimens were also balanced. The side effects observed in the chemotherapy arm were also consistent with the known profiles of platinum-based doublet chemotherapy.

Spigel concluded that the AIM-HIGH trial demonstrated that utilizing this 14-gene assay to precisely direct systemic adjuvant therapy in stage 1a through 2a nonsquamous NSCLC has the potential to substantially reduce the rates of early recurrence and death.

“Utilization of this 14-gene assay to precisely direct systemic adjuvant therapy in stage 1a through 2a nonsquamous non–small cell lung cancer may substantially reduce the rates of early recurrence and death,” Spigel said.

"An international, multicenter, prospective randomized trial of adjuvant chemotherapy for stage 1A-2A non-small cell lung cancer identified as high risk by a 14-gene molecular assay" by Dr. David Spigel, et al., American Society of Clinical Oncology Annual Meeting.

For more news on cancer updates, research and education, don’t forget to 

subscribe to CURE®’s newsletters here.

The AIM-HIGH trial demonstrated significant improvement in disease-free survival (DFS) for high-risk stage 1a to 2a nonsquamous non-small cell lung cancer (NSCLC) patients identified by a 14-gene molecular assay who received adjuvant chemotherapy. At 24 months, 96% of chemotherapy patients were alive without disease progression, compared to 79% in the observation group. This trial is the first to show DFS improvement using a molecular risk discriminator in early-stage NSCLC, highlighting the potential of targeted adjuvant therapy to reduce early recurrence and mortality rates.


Using a 14-gene test to guide chemotherapy significantly improved disease-free survival in patients with early nonsquamous lung cancer.


Sabrina Serani

Imfinzi With Chemo Produces Inconclusive Outcomes in Phase 3 Mesothelioma Study

Imfinzi Plus BCG Improves Disease-Free Survival in High-Risk NMIBC

Tecentriq Plus BCG Does Not Improve Outcomes in Some With Bladder Cancer

Targeted Chemo Improves Survival in Early-Stage Lung Cancer

Latest News