Nuanced Biomarker Tests and Immunotherapy Strategies May Usher ASCO 2025 Data Into the Clinic

As the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting drew to a close, top experts across oncology fields reflected on the data that signaled future developments regarding novel biomarker testing strategies, increasingly personalized modifications of standard chemotherapy regimens, and optimal use of PD-1/PD-L1 inhibition.

“We’re in interesting times,” Maurie Markman, MD, editor in chief of OncologyLive and president of medicine & science at City of Hope in Atlanta, Georgia; Chicago, Illinois; and Phoenix, Arizona, said. “The incredibly important and optimistic tone is our increasing understanding of the fundamental biology of cancer—what makes it start, what makes it grow, what makes it become resistant. Getting to the molecular biology of cancer has allowed insights that are now being translated into new drugs, new strategies, and monitoring approaches that are, without any question, increasingly having an effect on patients—not only on survival, which is a critical end point, but on the quality of the lives that the patients are experiencing.”

OncologyLive captured all angles of this year’s ASCO meeting in Chicago, Illinois, through our live article coverage, more than 100 exclusive interviews with leading experts across oncology specialties, and the inaugural round of the On the Clock social media video series hosted by MedNews Week’s Chandler Park, MD, FACP, and Yan Leyfman, MD. Read on for topline coverage of 19 of the most exciting abstracts from the conference, and visit onclive.com/conference/asco for additional comprehensive coverage.

For a full list of abstracts from the meeting, visit: bit.ly/4jHnKVB.

Breast Cancer

Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine- based therapy (ET) and ahead of disease progression in patients (pts) with HR+/ HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial (Abstract LBA4)

Findings from the phase 3 SERENA-6 trial (NCT04964934) revealed that the addition of the oral selective estrogen receptor degrader camizestrant to continued CDK4/6 inhibition significantly improved progression-free survival (PFS) compared with continuation of an aromatase inhibitor (AI) and a CDK4/6 inhibitor ahead of disease progression on first-line therapy in patients with estrogen receptor–positive, HER2-negative advanced breast cancer harboring an ESR1 mutation.

The median investigator-assessed PFS was 16.0 months (95% CI, 12.7-18.2) with camizestrant plus CDK4/6 inhibition (n = 157) vs 9.2 months (95% CI, 7.2-9.5) with continued AI plus CDK4/6 inhibition (n = 158; HR, 0.44; 95% CI, 0.31-0.60; P < .00001). The 12- and 24-month PFS rates in the camizestrant arm were 60.7% and 29.7%, respectively; the rates were 33.4% and 5.4% in the continued AI plus CDK4/6 inhibition arm.

Tess O’Meara, MD, MHS, Dana-Farber Cancer Institute

“Although the PFS and potentially [time to second progression] benefit looked good by switching from an AI to a different endocrine treatment earlier than progression…are we going to see longer overall survival [OS] and long-term outcomes for patients who switch their endocrine treatment up front? Or are we just getting into the next line of treatment earlier?”

How will our health care system be able to handle serial circulating tumor DNA [ctDNA] sequencing, especially outside of academic centers? How will patients respond to serial ctDNA testing adding to test anxiety and anticipation about their results? SERENA-6 brought up a lot of interesting questions about the ways we’re moving toward drug approval and how we’re going to define molecular response.”

Sara M. Tolaney, MD, MPH, Dana-Farber Cancer Institute

“This was a different way of thinking, [considering that] maybe we should look for molecular progression [and] emergence of resistance by liquid biopsies and then change treatment, rather than waiting until anatomic progression. These were interesting data because they showed that we can dramatically improve PFS and that quality of life was substantially better when switching at the time of molecular progression. We’re delaying the time to anatomic progression, which is delaying patients from getting symptoms from their disease. It’s an exciting study, and we’ll have to wait for approval, but if [camizestrant plus CDK4/6 inhibition] becomes an option, it would be a paradigm shift in the way we think about treating [patients with metastatic disease].”

Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study (Abstract LBA109)

The primary readout of the phase 3 ASCENT-04/ KEYNOTE-D19 study (NCT05382286) showed that the frontline combination of sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) compared with chemotherapy plus pembrolizumab in patients with PD-L1–positive, advanced or metastatic TNBC.

At a data cutoff date of March 3, 2025, the median PFS with sacituzumab govitecan plus pembrolizumab (n = 221) was 11.2 months (95% CI, 9.3-16.7) by blinded independent central review vs 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab (n = 222; HR, 0.65; 95% CI, 0.51-0.84; P < .001). In the sacituzumab govitecan arm, the respective 6- and 12-month PFS rates were 72% (95% CI, 65%-77%) and 48% (95% CI, 41%-56%); these respective rates in the chemotherapy arm were 63% (95% CI, 56%-69%) and 33% (95% CI, 26%-40%). The median overall survival was not reached (NR) in the sacituzumab govitecan arm (95% CI, 25.6 months-NR) or the chemotherapy arm (95% CI, NR-NR; HR, 0.89; 95% CI, 0.62-1.29).

Manmeet Singh Ahluwalia, MD, MBA, FASCO, Baptist Health Miami Cancer Institute

“I manage brain metastases, and patients with TNBC have limited options, especially when they get brain metastases. We have seen nice response rates with immunotherapy, and now we’re excited that we [may] have a combination of an antibody-drug conjugate [ADC] with immunotherapy. This opens doors for numerous combinations because ADCs have been transforming outcomes of patients with different cancers, including breast cancer…. The fact that now we have an ADC that can be combined with immune checkpoint blockade to show synergy of cell kill…opens numerous opportunities for patients with cancer and brain tumors.”

Gynecology

TRUST: Trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7) (Abstract LBA5500)

Data from the phase 3 TRUST trial (NCT02828618) showed that progression-free survival (PFS) outcomes were significantly improved with primary cytoreductive surgery (PCS) compared with neoadjuvant chemotherapy and interval cytoreductive surgery (ICS) in patients with advanced ovarian cancer.

The median PFS, a secondary end point, was 22.1 months (95% CI, 20.4-24.5) with PCS (n = 345) vs 19.7 months (95% CI, 17.9-21.9) with ICS (n = 343; HR, 0.80; 95% CI, 0.66-0.96; P = .018). This was also the first randomized trial to show an overall survival benefit with PCS vs ICS, although this difference was not statistically significant.

Bradley Monk, MD, FACOG, FACS, Florida Cancer Specialists & Research Institute

“The TRUST study confirms that there is no decrement in survival associated with neoadjuvant chemotherapy and interval debulking compared with primary debulking, even at high-volume, surgically qualified sites managing advanced ovarian cancer. This adds confidence to the role of neoadjuvant chemotherapy and interval debulking.”

Rachel N. Grisham, MD, Memorial Sloan Kettering Cancer Center

“In part due to the practice shift that occurred during the COVID-19 [pandemic], many practices have moved more routinely toward the use of neoadjuvant chemotherapy for treatment of women with advanced ovarian cancer. This study reinforces that primary cytoreductive surgery is the standard of care in nonfrail patients with potentially resectable advanced ovarian cancer.”

ROSELLA: A phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG- 3073, ENGOT-ov72) (Abstract LBA5507)

Data from the phase 3 ROSELLA trial (GOG-3073/ENGOT ov72/APGOT-Ov10/LACOG-0223/ ANZGOG-2221/2023; NCT05257408) showed that relacorilant plus nab-paclitaxel (Abraxane) significantly improved progression-free survival (PFS) and prolonged overall survival (OS) vs nab-paclitaxel alone in patients with platinum-resistant ovarian cancer.

The median PFS per blinded independent central review was 6.54 months (95% CI, 5.55- 7.43) with relacorilant plus nab-paclitaxel (n = 188) vs 5.52 months (95% CI, 3.94-5.88) with nab-paclitaxel alone (n = 193; HR, 0.70; 95% CI, 0.54-0.91; P = .0076). The interim data for OS, which were at 50% maturity, demonstrated that the median OS was 15.97 months (95% CI, 13.47-not reached) with relacorilant compared with 11.50 months (95% CI, 10.02-13.57) with nab-paclitaxel alone (HR, 0.69; 95% CI, 0.52-0.92; P = .0121).

Bradley Monk, MD, FACOG, FACS, Florida Cancer Specialists & Research Institute

“Relacorilant…is a new class of agent, a glucocorticoid receptor antagonist. It was associated with an unprecedented prolongation in OS at the interim analysis compared with the most active agent in this setting.”

Ramez N. Eskander, MD, University of California, San Diego, Moores Cancer Center

“We are excited to see this combination regimen emerge as a potentially new treatment strategy for patients with platinum-resistant, recurrent ovarian cancer. The regimen was also tolerable [and associated] with a low discontinuation rate.”

Gastrointestinal Cancers

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) (Abstract LBA5)

Findings from the phase 3 MATTERHORN trial (NCT04592913) demonstrated that perioperative treatment with durvalumab (Imfinzi) plus FLOT extended EFS compared with placebo plus FLOT in patients with resectable gastric or gastroesophageal junction adenocarcinoma.

At a median follow-up of 31.6 months (range, 0.0-48.1) in the durvalumab arm (n = 474) and 31.4 months (range, 0.0-48.1) in the placebo arm (n = 474), treatment with the combination of durvalumab and FLOT produced a median EFS that was not reached (NR; 95% CI, 40.7-NR) vs 32.8 months (95% CI, 27.9-NR) for placebo plus FLOT (HR, 0.71; 95% CI, 0.58-0.86; P < .001). In the durvalumab arm, the 18- and 24-month EFS rates were 73% and 67%, respectively. In the placebo arm, these rates were 64% and 59%, respectively.

Kohei Shitara, MD, National Cancer Center Hospital East

“OS [overall survival] data are still immature, but [durvalumab plus FLOT] already showed a benefit, especially in terms of long-term tail of the survival curve, and the HR already favors the combination arm at [0.78]. We need to wait for OS at the final analysis to conclude, but the current EFS data are attractive, and I consider this practice changing because EFS could be the true end point in the therapeutic setting. If I am a patient, I hope I can live without cancer. We need to wait for regulatory decisions, but I hope we can use this treatment in the near future.”

First-line encorafenib + cetuximab + mFOLFOX6 in BRAF V600E-mutant metastatic colorectal cancer (BREAKWATER): Progression-free survival and updated overall survival analyses (Abstract LBA3500)

Updated findings from the phase 3 BREAKWATER trial (NCT04607421) demonstrated that the addition of encorafenib (Braftovi) and cetuximab (Erbitux) to mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) generated a statistically significant and clinically meaningful progression-free survival (PFS) improvement vs standard of care (SOC) in patients with previously untreated, BRAF V600E–mutated metastatic colorectal cancer (mCRC).

At a median follow-up of 16.8 months (95% CI, 15.1-18.4) in the encorafenib/cetuximab/mFOLFOX6 arm (n = 236) and 9.8 months (95% CI, 8.5-13.0) in the SOC arm (n = 243), patients treated in the experimental arm achieved a median PFS of 12.8 months (95% CI, 11.2-15.9) vs 7.1 months (95% CI, 6.8-8.5) for those given SOC (HR, 0.53; 95% CI, 0.41-0.68; P < .0001).

Dirk Arnold, MD, PhD, Asklepios Tumorzentrum Hamburg

“The modification of standard chemotherapy with an active molecular-targeting agent in the first-line setting is of super importance, and we saw impressive data for a group of patients with BRAF V600 mutations in colon cancer. Here, giving the targeted agent in addition to chemotherapy led to a massive improvement in PFS and, by trend, also OS. That’s impressive to see how targeted approaches, even in a disease like CRC, can massively improve outcomes.”

Emil Lou, MD, PhD, FACP, Masonic Cancer Center, University of Minnesota

“[At] the 2025 ASCO Annual Meeting, more than most annual meetings… [gastrointestinal (GI) oncology] has risen to the top. BRAF long was a prognostic factor for CRC in 5% to 10% of cases of stage IV disease and has become targetable in more recent years. This study showed that the combination of chemotherapy and targeted therapy is making a major advance and extending how long patients live with that disease. This has turned a biomarker that was previously considered something patients would not want into something that is actionable and targetable with combination drug therapy. This has made our therapeutic options for patients in the clinic much more promising than before. A lot of the things we’re seeing in GI oncology are spanning from the lab and ctDNA [circulating tumor DNA] biomarkers all the way to actionable therapies and everywhere in between.”

Genitourinary Cancers

Phase 3 AMPLITUDE trial: Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes (Abstract LBA5006)

Data from the phase 3 AMPLITUDE trial (NCT04497844) showed that the combination of niraparib and abiraterone acetate (Akeega) plus prednisone reduced the risk of radiographic progression or death vs placebo plus abiraterone acetate and prednisone for patients with mCSPC harboring HRR gene alterations who had received prior androgen deprivation therapy.

At a median follow-up of 30.8 months, the median radiographic progression-free survival was not estimable for patients who received niraparib vs 29.5 months for those who received placebo (HR, 0.63; 95% CI, 0.49-0.80; P = .0001). The addition of niraparib also significantly reduced the risk of symptomatic progression vs placebo plus AAP (HR, 0.50; 95% CI, 0.36- 0.69; P < .0001).

Alicia Morgans, MD, MPH, Dana-Farber Cancer Institute

“Understanding the possible utility of a PARP inhibitor, and certainly a PARP inhibitor–based combination, in this metastatic hormone- sensitive setting is potentially meaningful for patients with [BRCA1 and BRCA2] mutations that inherently give them a poor prognosis and worse outcomes in terms of faster disease progression and perhaps more suffering in an overall shorter timeline in terms of survival. This combination…will be important for that patient population…who will then have something new to look to as a source of hope and opportunity in this setting.”

Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA (Abstract 4503)

Data from an exploratory analysis of the phase 3 NIAGARA trial (NCT03732677) investigating perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy and radical cystectomy vs neoadjuvant chemotherapy and radical cystectomy alone in patients with MIBC showed the potential utility of ctDNA as a biomarker that is prognostic for event-free survival (EFS) with the durvalumab combination.

At baseline, positive ctDNA levels were prognostic for EFS (HR 0.42; 95% CI, 0.30- 0.60). Throughout the study, treatment with durvalumab demonstrated an EFS benefit regardless of ctDNA status for ctDNA-negative patients (HR, 0.45; 95% CI, 0.24-0.84) and ctDNA-positive patients (HR, 0.73; 95% CI, 0.51-1.05). The rates of ctDNA clearance from baseline to precystectomy were 70% in the durvalumab arm vs 57% in the comparator arm. Furthermore, EFS outcomes were better in patients who cleared ctDNA prior to cystectomy (HR, 0.32; 95% CI, 0.22-0.47).

Alan Tan, MD, Vanderbilt University Medical Center

“We’ve reached new heights in bladder cancer, especially MIBC. In the NIAGARA data, looking at ctDNA…at baseline, [57% of patients] were ctDNA positive, emphasizing that this is a systemic disease, even though it’s stage II. MIBC requires neoadjuvant treatment, and ctDNA negativity is an important prognostic marker for patients who might do well with surgery. If they’re [ctDNA] positive, surgery might not be the right answer.”

Guru P. Sonpavde, MD, AdventHealth Cancer Institute

“[NIAGARA] led to a change in the SOC [standard of care] across many areas of the world. It’s not clear that [the findings presented at ASCO 2025] change standards because [patient] groups benefited from adding durvalumab regardless of ctDNA positivity or negativity. That’s interesting but does not change the SOC.”

Ipilimumab and nivolumab in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated on the phase 3 PDIGREE (Alliance A031704) trial: Results from Step 1 analysis (Abstract 4516)

The adaptive phase 3 PDIGREE study (NCT03793166) is investigating the sequential treatment of ipilimumab (Yervoy) plus nivolumab (Opdivo; step 1) followed by cabozantinib (Cabometyx) plus nivolumab vs nivolumab treatment adapted to 3-month radiographic responses (step 2) in patients with metastatic International Metastatic RCC Database Consortium (IMDC) intermediate- and poor-risk ccRCC.

Findings from the step 1 analysis showed that fewer patients with IMDC poor-risk disease and bone metastases were treated in step 2 than in step 1. Pending step 2 findings, this trial may inform the use of immunotherapy sequencing and adaptation based on radiographic response in this population.

Sumanta Kumar Pal, MD, FASCO, City of Hope

“Nivolumab plus ipilimumab [is associated with] a core complete response rate applied across a broad setting, not in clinical trials. [These findings] suggest that it is feasible to do studies like this where you’re taking a broad spectrum of patients and applying a novel treatment strategy, not necessarily in the initial treatment setting, but after [patients have] had a chance to be on therapy and respond to it.”

Lung Cancer

Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial (Abstract 8006)

Primary results from the phase 3 IMforte trial (NCT05091567) showed that first-line maintenance treatment with lurbinectedin (Zepzelca) in combination with atezolizumab (Tecentriq) improved progression-free survival (PFS) and overall survival (OS) vs atezolizumab monotherapy in patients with ES-SCLC.

The median PFS with lurbinectedin plus atezoli- zumab (n = 242) was 5.4 months (95% CI, 4.2-5.8) per independent review facility assessment vs 2.1 months (95% CI, 1.6-2.7) with atezolizumab monotherapy (n = 241; HR, 0.54; 95% CI, 0.43- 0.67; 2-sided P < .0001). The median OS was 13.2 months (95% CI, 11.9-16.4) with the doublet vs 10.6 months (95% CI, 9.5-12.2) with the monotherapy (HR, 0.73; 95% CI, 0.57-0.95; 2-sided P = .0174).

Eric K. Singhi, MD, The University of Texas MD Anderson Cancer Center

“Big changes are underway for patients with SCLC. The IMforte study delivered practice-changing results. However, careful toxicity monitoring will be essential, as higher rates of grade 3/4 adverse effects were observed with combination maintenance therapy, and this approach eliminates the chemotherapy-free interval that some patients previously benefited from.”

Alexander I. Spira, MD, PhD, FACP, FASCO, Virginia Cancer Specialists

“Maintenance lurbinectedin improved survival and offers [another] option for patients with SCLC [in a paradigm that] includes ADCs [antibody-drug conjugates], T-cell engagers, and chemotherapy—regardless of which modality ultimately emerges as the most effective.”

Stephen Liu, MD, Georgetown Lombardi Comprehensive Cancer Center

“Given the high attrition rate in SCLC, approximately half of patients never receive second-line therapy. Earlier use of active treatment, such as lurbinectedin, gives patients the chance to receive that benefit. With phase 3 studies showing a survival advantage with maintenance therapy and new second-line therapy options, there is more reason for optimism in SCLC.”

Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304 (Abstract LBA8008)

Findings from the primary analysis of the phase 3 DeLLphi-304 trial (NCT05740566) demonstrated that second-line treatment with tarlatamab-dlle (Imdelltra) generated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) vs chemotherapy in patients with SCLC.

At a median follow-up of 11.2 months in the tarlatamab arm (n = 254) and 11.7 months in the chemotherapy arm (n = 255), the median OS with tarlatamab was 13.6 months vs 8.3 months for chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; 2-sided P < .001). The median PFS in the tarlatamab arm was 4.2 months and 3.7 months in the chemotherapy arm (HR, 0.71; 95% CI, 0.59-0.86; 2-sided P = .002).

Stephen Liu, MD, Georgetown Lombardi Comprehensive Cancer Center

“This should be our SOC [standard-of-care] second-line therapy for eligible patients.”

Sandip P. Patel, MD, FASCO, University of California, San Diego, Moores Cancer Center

“There are some logistical hurdles in the administration of this agent at the current time, but given the significant benefit seen in this study, it’s important to provide access to tarlatamab for patients, as it currently is the most likely treatment we have to provide durable responses.”

Luis Raez, MD, FASCO, FACP, FCCP, Memorial Cancer Institute

“The DeLLphi-304 trial results were some of the most significant for the lung cancer community at ASCO 2025. Among patients with relapsed SCLC after progression on platinum-based chemotherapy, tarlatamab led to a greater OS, better PFS, and better overall response rate over conventional palliative chemotherapy, with an acceptable toxicity profile.”

Overall survival with neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) in patients with resectable NSCLC in CheckMate 816 (Abstract LBA8000)

Data from the phase 3 CheckMate 816 study (NCT02998528) showed that neoadjuvant nivolumab (Opdivo) plus chemotherapy yielded a statistically significant and clinically meaningful overall survival (OS) benefit vs chemotherapy alone in patients with resectable non–small cell lung cancer (NSCLC).

At a median follow-up of 68.4 months, the median OS was not reached with nivolumab plus chemotherapy (n = 179) compared with 73.7 months with chemotherapy alone (n = 179; HR, 0.72; 95% CI, 0.523-0.998; P = .0479). The 60-month OS rates in the nivolumab and chemotherapy-alone arms were 65% and 55%, respectively.

Martin F. Dietrich, MD, PhD, Cancer Care Centers of Brevard

“OS benefit with neoadjuvant chemotherapy/immunotherapy on the CheckMate 816 protocol demonstrates the critical nature of changing early-stage disease practice, with the neoadjuvant [patients] likely carrying most of the clinical benefit. This is a practice-changing trial result.”

Tina Cascone, MD, PhD, The University of Texas MD Anderson Cancer Center

“It is important to understand the long-term outcomes with an approach that is relatively easier than a perioperative strategy for patients. It will be important in the future to keep all this in mind to tailor [treatments] to our population and look at important other factors to make strategic decisions on how to treat patients with this option.”

Neoadjuvant (neoadj) osimertinib (osi) ± chemotherapy (CT) vs CT alone in resectable (R) epidermal growth factor receptor- mutated (EGFRm) NSCLC: NeoADAURA (Abstract 8001)

Findings from the phase 3 NeoADAURA trial (NCT04351555) showed that treatment with neoadjuvant osimertinib (Tagrisso) as monotherapy or in combination with chemotherapy significantly improved major pathological response (MPR) rates compared with chemotherapy alone in patients with resectable EGFR-mutated non–small cell lung cancer (NSCLC).

Patients treated with osimertinib plus chemotherapy (n = 121) achieved an MPR rate of 26% (95% CI, 18%-34%); this rate was 25% (95% CI, 17%-34%) among patients who received osimertinib monotherapy (n = 117) and 2% (95% CI, 0%-6%) among those who received placebo plus chemotherapy arm (n = 120).

Martin F. Dietrich, MD, PhD, Cancer Care Centers of Brevard

“NeoADAURA introduced targeted therapy with osimertinib into the neoadjuvant [NSCLC setting] with some interesting clinical results [that support this strategy] rather than [patients] receiving it months after surgery and chemotherapy.”

Hematology

Overall survival (OS) and duration of response for transfusion independence (TI) in erythropoiesis stimulating agent (ESA)–naive patients (pts) with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) treated with luspatercept (LUSPA) vs epoetin alfa (EA) in the COMMANDS trial (Abstract 6512)

Findings from the OS analysis of the phase 3 COMMANDS trial (NCT03682536) showed that treatment with luspatercept-aamt (Reblozyl) durably improved the overall rate and cumulative duration of red blood cell TI (RBC-TI) for a period of at least 12 weeks compared with epoetin alfa in patients with transfusion-dependent, ESA-naive, very low–, low-, or intermediate-risk MDS.

The rate of RBC-TI for at least 12 weeks was 76.4% in the luspatercept arm vs 55.8% in the epoetin alfa arm (OR, 2.8; 95% CI, 1.7-4.5; P < .0001). The median durations of the longest 12-week or greater RBC-TI interval were 126.6 weeks (95% CI, 81.0-154.1) and 86.7 weeks (95% CI, 55.9-105.9) in these respective arms (HR, 0.632; 95% CI, 0.434-0.919; P = .0156). The median cumulative durations of RBC-TI for at least 12 weeks in these respective arms were 150.0 weeks (95% CI, 119.6-256.0) and 95.1 weeks (95% CI, 74.9-180.1; HR, 0.523; 95% CI, 0.353-0.777; P = .0011]).

Naval G. Daver, MD, The University of Texas MD Anderson Cancer Center

“The original data have already been shown; these led to the FDA approval of luspatercept in the frontline setting. [At ASCO 2025], for the first time, we had the long-term survival follow-up. Luspatercept improved hemoglobin [levels], reduced transfusion requirements, had a better durability of hemoglobin response, and led to a significant improvement in OS.”

This is the first time that we have seen a randomized improvement in survival in a low-risk MDS study. This is going to be important because now we have to start thinking about whether we should be using a drug like luspatercept in patients who have anemia, even if they’re not transfusion independent, with the idea that there may be other biological mechanisms whereby [luspatercept yields] an improvement in survival. Is this just because of reduced transfusion requirement and patients having less anemia and less organ damage from transfusions, which leads to better survival? Or is there a direct biological effect of luspatercept? We do not know yet; that is being studied. However, either way, this is important for patients with low-risk MDS.”

SEQUOIA 5-year follow-up in arm C: Frontline zanubrutinib monotherapy in patients with del(17p) and treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (Abstract 7011)

Five-year follow-up data from arm C of the phase 3 SEQUOIA trial (NCT03336333) showed that treatment with zanubrutinib (Brukinsa) demonstrated durable efficacy in patients with CLL and SLL with 17p deletions (del17p).

The 5-year progression-free survival (PFS) rate among patients in this cohort (n = 110) was 72.2% (95% CI, 62.4%-79.8%). At a data cutoff of April 30, 2024, the median PFS with zanubrutinib was not reached. The respective 5-year PFS rates for patients with mutated IGHV (n = 36) and unmutated IGHV (n = 67) were 74.6% (95% CI, 56.9%-85.9%) and 70.7% (95% CI, 57.4%-80.6%).

Manali Kamdar, MD, University of Colorado School of Medicine

“It was encouraging that the 5-year follow-up showed that more than 75% of patients remained on zanubrutinib…. This shows that zanubrutinib is efficacious and tolerable in patients with del17p CLL.”

MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: Primary end points of the phase 3 MIDAS trial (Abstract 7500)

Findings from the phase 3 MIDAS trial (NCT04934475) showed that minimal residual disease (MRD) status–guided consolidation therapy with autologous stem cell transplant (ASCT) in combination with isatuximab-irfc (Sarclisa) plus carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Isa-KRd) following Isa-KRd induction therapy did not improve MRD outcomes compared with the continuation of Isa-KRd alone in patients with newly diagnosed MRD-negative multiple myeloma (NDMM).

The postinduction MRD negativity rate at 10^–6 sensitivity was 76% in patients who received consolidation Isa-KRd vs 73% in those who received ASCT plus Isa-KRd. Following consolidation, the MRD-negativity rates in these respective arms of the intent-to-treat population were 84% and 86% (P = .64). In the MRD-positive group, 40% of patients achieved MRD negativity after receiving single ASCT plus Isa-KRd vs 32% of those who underwent tandem transplant (P = .31).

Amrita Krishnan, MD, City of Hope

“The question about using MRD to guide clinical decision-making has always been important to us. Now we have a randomized trial suggesting that it can be effective. [Isa-KRd] did not seem to have an effect on MRD-negativity rates premaintenance [in patients with MRD-negative disease]. Similarly, in the patients who were MRD positive, tandem transplant didn’t seem to affect MRD rates. In the United States, tandem transplant [in this setting] has not been widely adopted, so that part of the trial is probably less [important in the US].”

Focusing on the MRD-negative part, it is notable that the transplant arm did not increase rates of MRD negativity. [However], we didn’t see the breakdown of high-risk cytogenetic subgroups, and that is key. [Additionally], this is MRD at 1 time point. It may not be sufficient, and what we need to see is sustained MRD negativity. Before we consider abandoning transplant, we need to see longer follow-up and more data. [This trial] was informative, but it should not be practice-changing yet.”

Prospective validation of end of treatment ctDNA-MRD by PhasED-Seq in DLBCL patients from a national trial (Abstract 7000)

Findings from a prospective trial showed that circulating tumor DNA–based minimal residual disease (ctDNA-MRD) assessed by phased variant enrichment and detection sequencing (PhasED-Seq) was prognostic for survival outcomes in patients with diffuse large B-cell lymphoma (DLBCL) who had received curative-intent first-line treatment.

The 26-month progression-free survival rate among patients who were ctDNA-MRD negative at end of treatment (EOT; n = 126) was 85% vs 15% among those who were ctDNA-MRD positive at the same time point (n = 34; HR, 11.03; 95% CI, 6.27-19.40; P < .0001). The 36-month overall survival rates in these respective arms were 92% and 41% (HR, 7.38; 95% CI, 3.72- 14.62; P < .0001).

Jeremy Abramson, MD, MMSc, Massachusetts General Hospital

“PhasED-Seq is a highly sensitive MRD assay. We have published data in small numbers that show that patients who are [MRD] undetectable at EOT have an excellent prognosis and low likelihood of relapse, whereas patients who are MRD detectable at EOT have a high likelihood of recurrence. That was validated in a large, prospectively collected cohort in Europe, where the MRD assay PhasED-Seq was performed at the end of induction chemoimmunotherapy, and it was the most powerful predictor of prognosis. It was more prognostic than the baseline International Prognostic Index score and even more prognostic than the EOT PET scan, because those EOT PET scans can have a number of false positive results.

“These data suggest that an MRD test at the end of induction therapy coupled with the PET scan can powerfully predict those patients at low likelihood of relapse, who can be reassured, vs those patients at high likelihood of relapse, who should today be followed closely. Ultimately, we should be targeting those patients for treatment at the time of MRD detectability to eradicate the MRD and prevent relapsed disease. Studies like that are ongoing using MRD at EOT to guide treatment intensification. Seeing these data and how important they are in prognosis makes me strongly believe that intervening based on this assay can improve outcomes. That’s the future in DLBCL management.”

Skin/Melanoma

Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC) (Abstract 6001)

Data from the phase 3 C-POST trial (NCT03969004) showed a statistically significant and clinically meaningful reduction in disease recurrence with adjuvant cemiplimab-rwlc (Libtayo) vs placebo in patients with high-risk CSCC following surgery and radiation therapy.

The median disease-free survival was not reached (95% CI, not estimable [NE]-NE) among patients who received cemiplimab (n = 209) vs 49.4 months (95% CI, 48.5-NE) among those who received placebo (n = 206; HR, 0.319; 95% CI, 0.199-0.511; P < .0001).

Ahmad Tarhini, MD, PhD, Moffitt Cancer Center

“The data from the C-POST study…were encouraging and practice-changing. Anti–PD-1 monotherapy has more uptake in the neoadjuvant setting, so [these findings] consolidate the neoadjuvant, as well as adjuvant, use of anti–PD-1 agents as monotherapy in this patient population.”

DREAMseq: A phase 3 trial of treatment sequences in BRAF V600-mutant (m) metastatic melanoma (MM)—Final clinical results (Abstract 9506)

Final clinical results from the phase 3 DREAMseq trial (NCT02224781) showed that the efficacy benefits observed with the immunotherapy-first treatment approach of nivolumab (Opdivo) plus ipilimumab (Yervoy) followed by dabrafenib (Tafinlar) plus trametinib (Mekinist) were sustained at 5 years of follow-up in patients with BRAF V600E–mutant metastatic melanoma.

The 5-year overall survival rate was 63.3% (95% CI, 55.4%-72.3%) in patients who received nivolumab plus ipilimumab followed by dabrafenib plus trametinib vs 33.9% (95% CI, 25.9%-44.3%) among those who received dabrafenib plus trametinib followed by nivolumab plus ipilimumab. The median progression-free survival with the respective first-line regimens was 26.7 months (95% CI, 11.2-47.3) vs 8.5 months (95% CI, 8.1-12.6).

Ahmad Tarhini, MD, PhD, Moffitt Cancer Center

“These [data] updates consolidate the trend that we should be using immunotherapy in most patients who have BRAF-mutant melanoma and extensive metastatic disease.”