The 2024 ESMO Congress not only provided a forum for the presentation of positive, practice-changing data but also for negative trial data that are equally poised to inform care in the solid tumor realm. Twenty-three physicians who sat down with OncologyLive at the meeting in Barcelona, Spain, highlighted the 23 most notable trials from ESMO, with the phase 3 MULTISARC (NCT03784014), NIAGARA (NCT03732677), CheckMate 067 (NCT01844505), ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), and KEYNOTE-522 (NCT03036488) trials getting multiple nods from those treating patients with sarcoma; melanoma; and cancers of the cervix, breast, and bladder.

“This year’s ESMO Congress included [data from] a lot of negative studies as well as early-phase studies using antibody-drug conjugates [ADCs], one of the most promising future avenues of targeted therapies,” Gemma Eminowicz, MBChB, MD, of University College London Hospitals NHS Foundation Trust in the United Kingdom, said. “However, most of the negative studies are interesting, as [their findings] contribute to bodies of evidence in helping to understand the biology of the disease and how to better personalize treatment approaches.”

One physician even noted that among the advancements showcased in Europe, it was data presented during the 2024 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer that caught his attention the most with their potential to push the lung cancer field forward. Data from the prespecified interim analysis of the phase 3 HARMONi-2 trial (AK112-303; NCT05499390) revealed that ivonescimab (SMT112) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs pembrolizumab (Keytruda) in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression.

“These [exciting data from ESMO] come in the context of other gains that we have had rapidly. Perhaps the biggest splash was just days ago at the 2024 IASLC World Conference on Lung Cancer with the ivonescimab data,” Jared Weiss, MD, of the University of North Carolina School of Medicine in Chapel Hill, said. “That seems to be all that anyone wants to talk about, and although it’s not an ESMO finding, that’s the real answer to the question [of what the most notable data are].”

Additional key findings presented at ESMO include those from the phase 3 LEAP-012 (NCT04246177) and POD1UM-303 (NCT04472429) trials. In LEAP-012, patients with intermediate-stage hepatocellular carcinoma who received lenvatinib (Lenvima) plus pembrolizumab and transarterial chemoembolization (TACE) experienced a statistically significant improvement in the primary end point of PFS compared with those who received placebo plus TACE; investigators noted this could represent a new regimen for this patient population.

In POD1UM-303, the addition of retifanlimab-dlwr (Zynyz) to standard of care (SOC) carboplatin/paclitaxel improved median overall survival (OS) vs placebo plus carboplatin/paclitaxel by 6 months in patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal who did not receive systemic chemotherapy; a strong trend toward statistical significance at data cutoff was also observed, and OS follow-up is ongoing.

Throughout the entirety of the ESMO Congress, OncologyLive was on the ground, conducting more than 50 exclusive interviews with key opinion leaders to capture all aspects of this year’s meeting. See topline coverage below of more than 20 exciting abstracts, and visit onclive.com/conference/esmo for comprehensive coverage of the data.

For a full list of abstracts, visit: bit.ly/4eA65g6

Breast Cancer

LBA18 - Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results

Treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) yielded considerable overall and intracranial activity among patients with HER2-positive metastatic breast cancer and stable and active brain metastases in the prospective, phase 3b/4 DESTINY-Breast12 study (NCT04739761).

Patients with baseline brain metastases (n = 263) achieved a 12-month PFS rate of 61.6% (95% CI, 54.9%-67.6%), and the post hoc analysis median PFS was 17.3 months (95% CI, 13.7-22.1). The 12-month PFS rates with the agent were consistent in those with stable (n = 157) and active (n = 106) brain metastases, at 62.9% (95% CI, 54.0%-70.5%) and 59.6% (95% CI, 49.0%-68.7%), respectively. Additionally, the 12-month OS rate was maintained as patients with brain metastases at baseline experienced a rate of 90.3% (95% CI, 85.9%) compared with 90.6% (95% CI, 86.0%-93.8%) in those without brain metastases.

Further data revealed that the central nervous system (CNS) overall response rate (ORR) was 71.7% (95% CI, 64.2%-79.3%) in patients with brain metastases at baseline (n = 138); those with stable brain metastases (n = 77) experienced a confirmed CNS ORR of 79.2% (95% CI, 70.2%-88.3%) vs 62.3% (95% CI, 50.1%-74.5%) in those with active brain metastases (n = 61).

Oleg Gluz, MD, Breast Center Niederrhein, Moers, Germany

“From the metastatic breast cancer [setting the most important data] are the DESTINYBreast-12 results for T-DXd in patients with brain metastases. In the early setting, OS results from the KEYNOTE-522 trial, which show an OS benefit for pembrolizumab in combination with neoadjuvant chemotherapy in patients with stage II/III triple-negative disease, [are notable. These] trials will have the most impact on clinical [practice].”

LBA4 - Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study

Findings from the KEYNOTE-522 trial demonstrated that neoadjuvant treatment with pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab, led to a statistically significant improvement in OS compared with neoadjuvant chemotherapy plus placebo, followed by adjuvant placebo, in patients with early-stage triple-negative breast cancer (TNBC).

Investigators noted these results further support the use of the pembrolizumab regimen as a SOC treatment for patients with high-risk, early-stage TNBC, as the perioperative pembrolizumab regimen reduced the risk of death by 34% vs the placebo regimen (HR, 0.66; 95% CI, 0.50-0.87; P = .00150). At a median follow-up of 75.1 months (range, 65.9-84.0), patients who received pembrolizumab (n = 784) experienced a 5-year OS rate of 86.6% (95% CI, 84.0%-88.8%) vs 81.7% (95% CI, 77.5%-85.2%) among patients in the placebo arm (n = 390). The OS benefit was observed across all key subgroups examined, and updated event-free survival (EFS) data also revealed a benefit with the pembrolizumab regimen vs placebo regimen (HR, 0.65; 95% CI, 0.51-0.83).

Maria Vittoria Dieci, MD, Istituto Oncologico Veneto IRCCS, Padua, Italy

“One important abstract [presented] the OS data of the KEYNOTE-522 trial, [which] evaluated the role of pembrolizumab added to neoadjuvant chemotherapy and continued in the adjuvant setting for patients with TNBC. We already knew that pembrolizumab improved pathologic complete response [pCR] rates, but most importantly, it improved probably [to a] larger extent EFS. However, OS is the most important end point, so these results are highly awaited because we know that it is also important to look at the data and see what the magnitude of improvement in OS is.”

Sibylle Loibl, MD, PhD, Goethe University of Frankfurt,Germany

“The OS benefit from neoadjuvant therapy [seen in] the KEYNOTE-522 trial where pembrolizumab was added to standard carboplatin-containing neoadjuvant chemotherapy [is notable,] and the improved outcomes are certainly something which has already changed practice.”

235MO - Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in younger patients (pts) with HR+/HER2− early breast cancer (EBC) in NATALEE

On the final day of the 2024 ESMO Congress, September 17, adjuvant ribociclib (Kisqali) plus an aromatase inhibitor (AI) received FDA approval based on data from the phase 3 NATALEE trial (NCT03701334) for the treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.

Findings from the trial presented at ESMO showed that this patient population experienced an invasive disease-free survival (iDFS) benefit regardless of age when treated for 3 years with ribociclib at 400 mg. Patients younger than 40 years, who have historically experienced worse outcomes, achieved a 3-year iDFS rate of 90.1% when given ribociclib plus a nonsteroidal AI (n = 250) vs 85.0% among those who received a nonsteroidal AI alone (n = 293; HR, 0.546; 95% CI, 0.321-0.929). Patients aged 40 or older experienced 3-year iDFS rates of 90.7% vs 87.9% when treated with the doublet (n = 2299) vs a nonsteroidal AI alone (n = 2259), respectively (HR, 0.780; 95% CI, 0.648-0.939).

Nicholas P. McAndrew, MD, MSCE, UCLA Health, Santa Monica, California

“The updated results of NATALEE, the 4-year landmark analysis, [are among] the biggest news [in breast cancer]. People were concerned about the relatively small difference in 3-year iDFS from the initial reporting and primary analysis of this study. We know that with estrogen receptor–positive, HER2-negative breast cancer, it is not within the first 5 years even that the majority of patients will experience recurrence we see that risk of recurrence going up to 10, 15, 20 years, and beyond, and so it’s this early starting of endocrine therapy and, in my opinion, CDK4/6 inhibitors being started at the beginning, that provide that initial widening of the survival curves depending on whether you add that [therapy]. We’re seeing that did substantially increase from approximately 2% to 3% to well over 5%, which is not too different than what was seen in the phase 3 monarchE study [NCT03155997] which included a higher-risk population than NATALEE, but [in that] population many of the patients in the control arm did not receive ovarian function suppression and an AI, which is now SOC in that population—so some patients did receive sub-standard endocrine therapy, making that delta more impressive in monarchE as compared with the NATALEE study. That’s one of the biggest findings from the conference.”

Sarcoma

1719O - MULTISARC: A randomized precision medicine study in advanced soft-tissue sarcomas

Findings from the phase 3 MULTISARC trial (NCT03784014) demonstrated the feasibility of high-throughput molecular profiling for patients with advanced soft tissue sarcoma when examining the utility of next-generation sequencing (NGS) given up front to guide personalized treatment strategies. According to investigators, findings showcased the potential of tailored therapies and personalized approaches for patients with soft tissue sarcoma; such approaches are critical, as over 100 histological subtypes of soft tissue sarcoma exist.

Comparative survival outcomes between the NGS arm and non-NGS arm will be reported in the future with results from additional subtrials as well, but data from ESMO revealed that among patients who received NGS (n = 181), 47% had at least 1 targetable alteration; 36% of these patients then received targeted investigational therapies. Additionally, 314 alterations were identified across 62 genes, and patients had a median of 2 alterations in the NGS arm. The most common histological subtypes included leiomyosarcoma (23.9%), liposarcoma (23.0%), and undifferentiated pleiomorphic sarcoma (15.3%) among patients in the trial (n = 439), and 14% of patients in the NGS arm had a transcriptomic tertiary lymphoid structure signature.

J. Andrew Livingston, MD, MS, The University of Texas MD Anderson Cancer Center, Houston

“I was especially excited to see the data for the MULTISARC study from the French Sarcoma Group looking at what the role of NGS or profiling is in sarcomas. Many of us often use this in the clinic, and this was a nice study prospectively looking at patients who either had NGS testing [done] or didn’t in the advanced metastatic setting [to] understand what the utility of that is. Why does that have such a big implication for our field? One, we [could] see what the frequency is of these so-called actionable alterations in approximately half the patients they profiled, and many of those patients were then able to go on to matched therapies on clinical trials. I believe this is how our field is evolving: better understanding subtype-specific treatment, looking at molecular profiling, and looking [at] match therapies. Hopefully this will be a call to action where we’ll see more match therapy trials available so that when we profile patients, we can get them onto those other treatments because that’s where we’re seeing the greatest efficacy.”

Elise F. Nassif Haddad, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston

“One abstract [with data] that is not yet practice changing but is extremely promising for the future is on the MULTISARC trial…. [Findings] showed that we will identify a therapeutic target in up to 50% of [the] patients we do NGS for, and a subgroup analysis showed [there was] prolonged disease control by doing this approach. Although this is still preliminary and not readily translatable in the clinic because it depends on which biomarkers you’re looking at, it’s the future. The future is exactly this—to look at the genomic sequencing for our patients and tailor our treatments to genomic sequencing [results]. This approach holds a lot of promise, and I’m very excited about this trial.”

1718O - EREMISS trial: A double-blind placebo (PBO)-controlled randomised trial assessing efficacy/safety of regorafenib (REGO) as maintenance therapy after 1st line doxorubicin-based chemotherapy in advanced soft-tissue sarcoma (ASTS) patients (pts)

The phase 2 EREMISS trial (NCT03793361) met its primary end point as regorafenib (Stivarga) maintenance therapy significantly improved PFS vs placebo in patients with advanced soft tissue sarcoma following 6 cycles of frontline doxorubicin-based chemotherapy.

The median PFS by blinded central radiological review was 5.6 months (95% CI, 3.9-8.2) in the regorafenib arm (n = 60) vs 3.5 months (95% CI, 1.8-3.6) in the placebo arm (n = 62; adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). The 6- and 12-month PFS rates were 49.5% (95% CI, 36.0%-61.7%) and 14.7% (95% CI, 6.7%-25.6%) in the regorafenib arm compared with 14.6% (95% CI, 7.0%-24.9%) and 7.3% (95% CI, 2.4%-16.0%) in the placebo arm, respectively. Findings also revealed that the PFS benefit was not significantly different based on response to prior chemotherapy or histologic subtype.

Additionally, a nonsignificant difference in OS was observed with a median OS of 27.6 months (95% CI, 19.9-33.0) seen among those who received regorafenib vs 20.5 months (95% CI, 15.8-25.1) among those given placebo (adjusted HR, 0.78; 95% CI, 0.50-1.22; P = .28).

Javier Martín-Broto, MD, PhD, University Hospital Fundacíon Jiménez Díaz, Madrid, Spain

“There were several good publications this year—there were 3 comparative trials in sarcoma, which is a substantial number for one congress, and several phase 2 trials which are also interesting in sarcoma. The most [impactful one] is the EREMISS trial, introducing the concept of maintenance [therapy] with regorafenib in the first-line setting of advanced soft tissue sarcoma, and this is a necessary concept to put on the table because this could mean a longer PFS [for patients]. This has also been proven in leiomyosarcoma with the combination of doxorubicin/trabectedin [Yondelis] and then maintenance trabectedin, and now [it is proven] with regorafenib; obviously not [at] a full dose, but 120 mg could be a novelty and could also mean a jump toward better survival. This is the top study in this edition of the ESMO Congress in sarcoma.”

Lung

LBA54 - Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non–small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2

Longer-term follow-up data from the second interim analysis of the phase 3 MARIPOSA-2 study (NCT04988295) confirmed the benefit of amivantamab-vmjw (Rybrevant) plus chemotherapy vs chemotherapy alone in patients with EGFR-mutated advanced NSCLC who experienced disease progression on osimertinib (Tagrisso).

At a median follow-up of 18.1 months, significant and sustained improvements were seen with the doublet vs monotherapy regarding time to symptomatic progression (HR, 0.73; 95% CI, 0.55-0.96; P = .026), time to treatment discontinuation (HR, 0.42; 95% CI, 0.33-0.53; P < .0001), time to subsequent therapy (HR, 0.51; 95% CI, 0.39-0.65; P < .0001), and PFS after first subsequent therapy (HR, 0.64; 95% CI, 0.48-0.85; P = .002). A trend in improved OS with the doublet vs chemotherapy was also seen, as patients in the amivantamab plus chemotherapy arm (n = 131) achieved a median OS of 17.7 months (95% CI, 16.0-22.4) vs 15.3 months (95% CI, 13.7-16.8) in the chemotherapy alone arm (n = 263; HR, 0.73; 95% CI, 0.54-0.99; P = .039). The 18-month OS rates were 50% vs 40%, respectively.

Sanjay Popat,MBBS, PhD, BSc, FRCP, The Royal Marsden,London, England

“Perhaps one of the most important studies at ESMO this year was the updated survival analysis of MARIPOSA-2 because, in this setting, we know that the combination of chemotherapy and amivantamab markedly improves PFS, but here we demonstrated that there was a clear and improved survival trend with a HR of 0.73; this did not quite meet statistical significance but that’s because of the amount of α spend that we used in the statistical design to allow for maximum power for OS at the final analysis. There’s a clear and meaningful survival trend with the combination of amivantamab with chemotherapy over chemotherapy alone.”

1253O - Phase I/II ALKOVE-1 study of NVL-655 in ALK-positive (ALK+) solid tumours

Treatment with the potent, ALK-selective tyrosine kinase inhibitor (TKI) NVL-655 demonstrated encouraging activity in heavily pretreated patients with advanced ALK-positive NSCLC, including those who previously received lorlatinib (Lorbrena), according to findings from the phase 1/2 ALKOVE-1 study (NCT05384626). In the phase 1 portion of the trial, the TRK-sparing inhibitor was well tolerated, and 150 mg given once daily was established as the recommended phase 2 dose (RP2D).

Patients who received the agent at any dose level (n = 103) experienced an ORR of 38% at the conclusion of the dose-escalation phase, and those who received the RP2D of NVL-655 (n = 39) also achieved an ORR of 38%. Further, among patients with the G1202R ALK–resistance mutation (n = 32), the ORR was 69% across all dose levels and 71% at the RP2D (n = 14). Those who previously received lorlatinib experienced an ORR of 35% treated at all dose levels (n = 85) and the RP2D (n = 31). Rates among those who did not receive lorlatinib were 53% and 57% at all dose levels (n = 17) and the RP2D (n = 7), respectively. Responses were durable, as the median duration of response (DOR) was not reached (NR) in RP2D groups, with a 100% DOR seen at 6 months. Additionally, intracranial responses also occurred.

Benjamin Besse, MD, PhD, Gustave Roussy, Villejuif, France

“One of my takeaways from ESMO 2024 will be on the new ALK inhibitors that have been presented, in particular NVL-655, a next-generation ALK inhibitor with a good safety profile and activity in patients pretreated [with ALK-targeting TKIs]. It is, so far, probably [a] best-in-class ALK inhibitor but with some adverse effects [AEs]. It brings a lot of hope to see new ALK inhibitors [that are] more potent, maybe with a more tolerable safety profile, come to us oncologists.”

Gynecological Cancers

709O - Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

Pembrolizumab given with chemoradiotherapy and then continued as monotherapy led to a statistically significant improvement in survival vs chemoradiotherapy alone in patients with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer. Updated data from the second interim analysis of the KEYNOTE-A18 study revealed that at a median follow-up of 29.9 months (range, 12.8-43.0), the median OS was NR in both arms (HR, 0.67; 95% CI, 0.50-0.90; P = .0040).

The 36-month OS rate was 82.6% (95% CI, 78.4%-86.1%) with pembrolizumab plus chemoradiotherapy (n = 529) vs 74.8% (95% CI, 70.1%-78.8%) with chemoradiotherapy alone (n = 531). Notably, the HR for death was under 1 in all protocol-specified subgroups, except among patients 65 years and older (HR, 1.35; 95% CI, 0.58-3.11). Investigators concluded that the data from KEYNOTE-A18 support pembrolizumab with concurrent chemotherapy as a new SOC for patients with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer.

Angeles Alvarez Secord, MD, MHSc, Duke Health, Durham, North Carolina

“Updated OS data from the KEYNOTE-A18 study [are] incredibly exciting because we’re really moving the needle, and that trial shows that by adding pembrolizumab, we can help our patients live longer.”

Gemma Eminowicz, MBChB, MD, University College London Hospitals NHS Foundation Trust, United Kingdom

“The presentation of data from the KEYNOTE-A18 study adding pembrolizumab to chemoradiation in patients with high-risk locally advanced cervical cancer was of great significance. But questions remain regarding why the patients with stage III and IV [disease] seem to get more benefit as well as patterns of relapse and radiotherapy quality with long overall treatment times and low rates of interstitial needle use.”

LBA28 - ENGOT-en11/GOG-3053/KEYNOTE-B21: A phase III study of pembrolizumab or placebo in combination with adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

The addition of pembrolizumab to adjuvant chemotherapy did not result in improved DFS outcomes in the intention-to-treat (ITT) population of patients with newly diagnosed, high-risk endometrial cancer following surgery in the phase 3 KEYNOTE-B21 study (NCT04634877). However, patients with mismatch repair–deficient (dMMR) disease experienced a benefit.

Data from the interim analysis of the trial showed that the median DFS was NR (95% CI, NR-NR) in both the pembrolizumab plus chemotherapy arm (n = 545) and the placebo plus chemotherapy arm (n = 550; HR, 1.02; 95% CI, 0.79-1.32; P = .570). In the dMMR subgroup, the median DFS was NR (95% CI, NR-NR) in the pembrolizumab arm (n = 141) and NR (95% CI, 29.5-NR) in the control arm (n = 140), but fewer events occurred in the investigative vs control arm (HR, 0.31; 95% CI, 0.14-0.69). In the MMR-proficient subgroup, the median DFS was also NR (95% CI, NR-NR) in both arms, but more events occurred in the investigative vs control arm (HR, 1.20; 95% CI, 0.91-1.57). Additionally, OS data were not mature at this time.

Gemma Eminowicz, MBChB, MD, University College London Hospitals NHS Foundation Trust, United Kingdom

“The presentation of data from KEYNOTE-B21 was particularly noteworthy, using pembrolizumab in addition to chemotherapy in the adjuvant setting for patients with high-risk endometrial cancer, as this showed negative results but a HR of 0.3 for patients with dMMR disease, which is consistent with other immuno-oncology [IO] data in dMMR settings. This is important as a reminder that carboplatin and paclitaxel still have a significant role in endometrial cancer as well as opening the question of [immunotherapy] in the targeted adjuvant setting.”

Head and Neck Cancer

851MO - Final analysis of a phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of the head and neck (JCOG1008)

The final analysis of the phase 2/3 JCOG1008 trial (jRCTs031180135)confirmed the noninferiority in OS of cisplatin plus radiation therapy given 3 times a week vs weekly in patients with squamous cell carcinoma of the head and neck, supporting the use of the regimen weekly as a SOC following surgery in those with high-risk, locally advanced disease.

At a median follow-up of 5.6 years, the 5-year OS rates were 58.7% (95% CI, 49.8%-66.6%) in the 3-times-a-week dosing arm (n = 132) vs 71.2% (95% CI, 62.5%-78.2%) in the once-a-week arm (n = 129; stratified HR, 0.76; 95% CI, 0.52-1.12; 1-sided for noninferiority P = .0024). Five-year follow-up data showed that late toxicities occurred at any grade in the 3-times-a-week (n = 129) vs once-a-week (n = 121) dosing arms safety population at rates of 91.5% vs 94.2%, respectively. Grade 3 to 4 toxicities occurred in 10.1% vs 13.2% of patients, respectively.

Nabil Saba, MD, FACP, Winship Cancer Institute of Emory University, Atlanta, Georgia

“There are not too many earth-shaking abstracts at this ESMO meeting, [but] we’ve seen [the examination of] cisplatin dosing, [which] we keep coming [back] to. Updates [presented] from [JCOG1008] data on postoperative cisplatin given every 3 weeks vs weekly showed maintenance of the benefits that we’ve seen in the previous report, [that weekly cisplatin plus radiotherapy was noninferior].”

LBA37 - Final results: Randomized assessment of cisplatin dosing interval for ototoxicity (RADIO) trial comparing chemoradiation (CRT) with cisplatin q3weekly to weekly for locally advanced squamous cell carcinoma of the head and neck (LASCCHN)

Final results from the RADIO trial (NCT03649048) confirmed that patients with locally advanced squamous cell carcinoma of the head and neck experienced less hearing impairment and tinnitus when treated with weekly cisplatin given concurrently with radiation therapy vs 3-times-a-week dosing given concurrently with radiation therapy.

Grade 2 or higher hearing impairment occurred in 64.0% of patients who received cisplatin 3 times a week at 100 mg/m2 intravenously on days 1, 22, and 43 with radiation therapy (n = 50) vs 40.8% among patients who received cisplatin weekly at 40 mg/m2 intravenously with radiation therapy (n = 49; OR, 0.39; 95% CI, 0.17-0.87; P = .021). Grade 3 toxicities occurred at similar rates in both arms at 38% vs 45%, respectively. Additionally, nonstatistically significant effects favoring the weekly dosing regimen vs 3 times a week were seen regarding hearing-related quality of life and the need for hearing amplification.

Nabil Saba, MD, FACP, Winship Cancer Institute of Emory University, Atlanta, Georgia

“The [RADIO] study looking at weekly vs every-3-weeks [administration of cisplatin] has very interesting results in terms of hearing toxicity with the every-3-week [regimen data], that is an eye-opener, [because] the more we study these 2 regimens, the more we realize they’re not the same. We’re waiting for more definitive trials, but this trial is compelling in terms of hearing loss [data].”

847O - Sequential chemoradiotherapy versus induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicentre, open-label, non-inferiority, randomised, phase III trial

A phase 3 noninferiority trial (NCT03366415) revealed that sequential chemoradiotherapy resulted in noninferior 3-year failure-free survival (FFS) rates vs induction chemotherapy followed by concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. In the ITT population, patients who received the investigative approach of sequential chemoradiotherapy (n = 210) experienced a 3-year FFS rate of 83.7% vs 79.5% among those who received the standard approach of induction chemotherapy followed by concurrent chemoradiotherapy (n = 210; HR, 0.77; 95% CI, 0.50-1.19; P = .244).

Investigators noted that sequential chemoradiotherapy could be considered an alternative treatment option for patients with nasopharyngeal carcinoma as it offers an advantage with reduced severity of nonhematological AEs during treatment. Common grade 3 AEs in the investigative vs control arms included mucositis (28.6% vs 41.9%), nausea (9.5% vs 18.1%), dermatitis (5.7% vs 4.3%), and vomiting (3.8% vs 9.5%), respectively.

Yungan Tao, MD, Institut Gustave Roussy, Villejuif, France

“A phase 3 trial in nasopharyngeal cancer with induction chemotherapy followed by radiotherapy vs induction chemotherapy followed by chemoradiotherapy in locally advanced nasopharyngeal cancer [was notable]. The result is, after induction with chemotherapy, we could replace the chemoradiotherapy [with] radiotherapy alone to reduce the toxicity, and this is a great phase 3 trial with approximately 500 patients included. It is probably the biggest news from this ESMO in the head and neck domain.”

849O - Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent/metastatic salivary gland cancer: Results from the MYTHOS trial

T-DXd yielded promising efficacy in patients with HER2-positive recurrent or metastatic salivary gland cancer, according to data from the phase 2 MYTHOS trial (jRCT2011210017). Patients treated with the ADC (n = 19) experienced a confirmed ORR of 68.4% (95% CI, 43.4%-87.4%), which consisted of a 10.5% CR rate and a 57.9% partial response rate by independent central review (ICR); the disease control rate was 100% (95% CI, 82.4%-100.0%). By investigator assessment, the ORR was 78.9% (95% CI, 54.4%-93.9%).

Patients also experienced a median PFS of 15.9 months (95% CI, 5.8-not estimable [NE]) by ICR, and the median duration of treatment was 10.4 months (range, 2.1-20.7). MYTHOS is ongoing and OS and PFS will be assessed with additional follow-up from the cohort that was presented at ESMO, cohort 1. The primary analysis will also be conducted for cohort 2, which enrolled patients with HER2-low disease.

Barbara Burtness, MD, Yale Cancer Center, New Haven, Connecticut

“The most intriguing results that we saw for head and neck cancer at ESMO this year had to do with the management of salivary gland cancer. The MYTHOS study for HER2-expressing salivary gland cancers was presented by Ichiro Kinoshita, MD, PhD, and this data with T-DXd showed a striking ORR of [68%]. Given the approval in the US for [this] agent in HER2-overexpressing cancers, we may find it quite straightforward to begin using this therapy.”

LBA36 - A randomised phase II study to evaluate the efficacy and safety of androgen deprivation therapy (ADT) vs chemotherapy (CT) in patients with recurrent and/or metastatic, androgen receptor (AR) expressing, salivary gland cancers

The phase 2 EORTC 1206-HNCG trial (NCT01969578) was the first randomized study ever completed in patients with androgen receptor (AR)-expressing salivary gland cancer, and data from the study showed that androgen deprivation therapy (ADT) was not superior nor inferior to chemotherapy in patients who were treatment naive.

Regarding the primary end point of PFS in patients who were treatment naive, the median PFS was 4.0 months (95% CI, 3.6-8.7) in the ADT arm (n = 26) vs 6.5 months (95% CI, 5.3-8.6) in the chemotherapy arm (n = 28; HR, 1.12; 80% CI, 0.77-1.63; P = .6536). Furthermore, the median OS was 22.4 months (95% CI, 14.3-27.7) vs 29.4 months (95% CI, 16.6-NE), respectively (HR, 1.91; 80% CI, 1.18-3.09; P = .9580). Additional data showed that previously treated patients enrolled in cohort B who received ADT (n = 46) experienced a median PFS of 3.5 months (95% CI, 2.0-5.9) and a median OS of 20.2 months (95% CI, 9.8-29.5).

Barbara Burtness, MD, Yale Cancer Center, New Haven, Connecticut

“The randomized phase 2 trial from EORTC was another study that closed early with less than expected accrual, so perhaps it was a little underpowered, but it was a very interesting study for patients with AR-positive salivary gland cancer comparing ADT with chemotherapy. I was surprised at how high the response rate was for chemotherapy. I believe the study is not definitive, but it did show a slightly higher response rate and better disease control with chemotherapy than ADT. The toxicity was greater for chemotherapy, but it’s a decision one has to make in shared decision-making with patients. [However], the likelihood that I would offer frontline chemotherapy to a patient with AR-positive disease just went up in the wake of these data.”

Genitourinary Cancers

LBA75 - Prospective randomised phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer: Results of the SUNNIFORECAST trial

Patients with non–clear cell renal cell carcinoma (RCC) who received ipilimumab (Yervoy) plus nivolumab (Opdivo) experienced a significant improvement in the 12-month OS rate compared with those who received SOC therapies, meeting the primary end point of the phase 2 SUNNIFORECAST trial (NCT03075423).

At a median follow-up of 24.3 months (range, 0.5-70.2), patients who received ipilimumab plus nivolumab (n = 157) achieved a 12-month OS rate of 86.9% (95% CI, 80.24%-91.46%) vs 76.8% (95% CI, 68.62%-83.09%) among those treated with SOC (n = 152; P = .0141). Patients in the doublet arm experienced a median OS of 42.4 months (95% CI, 35.24-55.54) vs 33.9 months (95% CI, 25.52-NE) in the SOC arm (P = .292). Additionally, the median PFS in the combination arm was 5.52 months (range, 4.30-8.23) compared with 5.65 months (range, 5.49-8.46) in the SOC arm (HR, 0.99; 95% CI, 0.76-1.18). The respective ORRs were 32.8% vs 19.6% (P = .001).

Eric Jonasch, MD, The University of Texas MD Anderson Cancer Center, Houston

“One of the interesting studies presented was looking at ipilimumab plus nivolumab vs SOC in non–clear cell RCC. The primary end point of 1-year survival was superior to the SOC. This is a set of disease subtypes that have tremendous unmet need, so this is providing a bit more evidence that perhaps ipilimumab plus nivolumab is a choice in that patient population.”

LBA68 - Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial

A statistically significant improvement in radiographic progression-free survival (rPFS) occurred when darolutamide (Nubeqa) was added to ADT vs placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (HSPC), meeting the primary end point of the phase 3 ARANOTE trial (NCT04736199). Investigators of the trial noted that darolutamide plus ADT without docetaxel should become an additional SOC for this patient population.

Treatment with the combination reduced the risk of radiological progression or death by 46% compared with the placebo arm, as patients in the darolutamide arm (n = 446) achieved a median rPFS of NR (95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR) in the placebo arm (n = 223; HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The 24-month rPFS rates were 70.3% vs 52.1%, respectively. The doublet also demonstrated a benefit vs placebo plus ADT across all secondary end points in patients with metastatic HSPC, including regarding median OS (stratified HR, 0.81; 95% CI, 0.59-1.12), time to metastatic castration-resistant prostate cancer (CRPC; stratified HR, 0.40; 95% CI, 0.32-0.51), and time to prostate-specific antigen progression (stratified HR, 0.31; 95% CI, 0.23-0.41).

Fred Saad, MD, FRCS, University of Montreal Hospital Center, Quebec, Canada

“The ARANOTE study, [which I presented], has the potential [to be] one of the low-hanging fruits of introducing another therapeutic option that’s very important for patients. ARANOTE is one of the studies that will have the biggest impact [from] ESMO for patients with prostate cancer. There are a lot of other very important studies that are being presented that in the future might make a change, but for now, I believe this is the one closest to being able to help patients in the real world.”

LBA1 - A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3

Data from the phase 3 PEACE-3 trial (NCT02194842) showed that the addition of radium-223 (Xofigo) to enzalutamide (Xtandi) yielded significant improvements in rPFS and OS in patients with metastatic CRPC and predominant bone metastases, with a statistically significant improvement seen regarding the primary end point of rPFS.

Patients who received radium-223 plus enzalutamide (n = 222) achieved a median rPFS of 19.4 months (95% CI, 17.1-25.3) vs 16.4 months (95% CI, 13.8-19.2) in the enzalutamide-alone arm (n = 224; HR, 0.69; 95% CI, 0.54-0.87; log-rank P = .0009). The 24-month rPFS rates were 45% vs 36%, respectively. Findings from the interim analysis, when 80% of OS events occurred, showed a significant improvement in OS, with a median OS of 42.3 months (95% CI, 36.8-49.1) observed in the doublet arm vs 35.0 months (95% CI, 28.8-38.9) in the monotherapy arm (HR, 0.69; 95% CI, 0.52-0.90; log-rank P = .0031).

Fred Saad, MD, FRCS, University of Montreal Hospital Center, Quebec, Canada

“The really exciting thing is there are a lot of very good data being presented in prostate cancer; we haven’t seen this much new data [in a while] and one [trial] that we’re very proud of is the PEACE-3 trial combining enzalutamide with radium-223. That has shown very positive results that will excite a lot of people.”

LBA5 - A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA)

Findings from the first phase 3 perioperative immunotherapy study conducted in muscle-invasive bladder cancer (MIBC) showed that treatment with neoadjuvant durvalumab (Imfinzi) plus chemotherapy followed by radical cystectomy and adjuvant durvalumab yielded a statistically significant improvement in EFS and OS vs neoadjuvant chemotherapy followed by radical cystectomy.

Patients with cisplatin-eligible MIBC treated in the NIAGARA study achieved a median EFS of NR (95% CI, NR-NR) when given the durvalumab regimen (n = 533) vs 46.1 months (95% CI, 32.2-NR) with the chemotherapy regimen (n = 530) by BICR (HR, 0.68; 95% CI, 0.56-0.82; P < .0001). The pCR rates at the April 2024 reanalysis were 37.3% (95% CI, 33.2%-41.6%) vs 27.5% (95% CI, 23.8%-31.6%), respectively (OR, 1.60; 95% CI, 1.23-2.08; nominal P = .0005), showing nominal statistical significance in favor of the durvalumab vs chemotherapy arm. OS benefits were also seen with the durvalumab vs chemotherapy regimen (HR, 0.75; 95% CI, 0.59-0.93; stratified log-rank P = .0106).

Andrea Necchi, MD, San Raffaele Hospital and Scientific Institute, Milan, Italy

“The biggest news in bladder cancer is the NIAGARA study. The durvalumab/chemotherapy neo[adjuvant] study provided an improvement in [EFS] and OS in patients with muscle-invasive disease as compared with SOC neoadjuvant chemotherapy. Clearly, [this is] a new therapeutic option for the patients.”

Guru Sonpavde, MD, AdventHealth Cancer Institute, Orlando, Florida

“In bladder cancer, the key study is NIAGARA…. We would expect this to be practice changing. If this comes into the clinic, I would expect [that] other chemotherapy/IO regimens being evaluated—such as enfortumab vedotin-ejfv [Padcev] plus pembrolizumab, gemcitabine/cisplatin plus nivolumab, [and] gemcitabine/cisplatin plus pembrolizumab—[will have a high] potential to be positive over the following few months [or] year, given that NIAGARA is positive. What effect this will have on adjuvant therapy [and] first-line therapy needs to be hashed out because checkpoint inhibition is going into an earlier space. How we treat patients who progress after prior immune checkpoint inhibition is a question to be answered and where we have to tread carefully, as we know, in RCC, repeating the immune checkpoint inhibitor in patients who progressed after immune checkpoint inhibition did not seem to benefit these patients when a VEGF inhibitor was added to continuation of a PD-1 or PD-L1 inhibitor.”

Gastrointestinal Cancers

LBA24 - Neoadjuvant immunotherapy in locally advanced MMR-deficient colon cancer: 3-year disease-free survival from NICHE-2

Findings from the phase 2 NICHE-2 study (NCT03026140) revealed that patients with high-risk, locally advanced dMMR colon cancer experienced an unprecedented 3-year DFS rate of 100% at a median follow-up from surgery of 36.6 months following treatment with 2 cycles of neoadjuvant immunotherapy. Although SOC adjuvant chemotherapy is typical for this patient population, 3-year recurrence rates are approximately 20% to 40%.

Further data from NICHE-2 showed that all patients enrolled were circulating tumor DNA (ctDNA) negative at the minimal residual disease time point of 3 weeks after surgery, and 45% of patients had cleared ctDNA after 1 cycle of therapy. Additionally, 98% of the 111 patients who received nivolumab plus ipilimumab in the first cycle of treatment followed by nivolumab monotherapy in the second cycle and then surgery experienced a pathologic response; a pCR occurred in 68% of patients.

John Strickler, MD, Duke Cancer Institute, Durham, North Carolina

“I really enjoyed seeing the update from NICHE-2 that was presented by Myriam Chalabi, MD, and her group, showing a 3-year DFS [rate] of 100% for patients who have [dMMR] localized colon cancer. These are very impressive data that are also provocative because it’s not currently the SOC, but with [these] data being so strong, it will continue to put some pressure on us to consider that as an option for certain patients.”

LBA58 - A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG

The first randomized phase 3 trial of neoadjuvant chemoradiotherapy in gastric cancer, TOPGEAR (NCT01924819), demonstrated that neoadjuvant chemoradiotherapy does not affect rates of curative resection, and adding it to perioperative chemotherapy did not improve OS.

The median OS among patients with gastric cancer in the neoadjuvant chemoradiotherapy arm (n = 286) was 46.4 months (95% CI, 35-61) vs 49.4 months (95% CI, 39-66) in the perioperative chemotherapy–alone arm (n = 288; HR, 1.05; 95% CI, 0.83-1.31; log-rank P = .70). Additionally, the 3-year OS rates were 55.1% vs 57.7%, respectively, and the 5-year rates were 44.4% vs 45.7%. Patients who received neoadjuvant chemoradiotherapy experienced a median PFS of 31.4 months vs 31.8 months in those who received perioperative chemotherapy alone. Investigators also noted that neoadjuvant chemoradiotherapy increased the pCR rate and tumor downstaging.

Trevor Leong, MBBS, MD, FRANZCR, Peter MacCallum Cancer Centre, Melbourne, Australia

“[TOPGEAR findings are] probably a bit disappointing for radiation oncologists in that [the investigative regimen] didn’t improve survival. [However], the trial will be practice changing because there are centers in the world—particularly in the US—that use preoperative radiation as the standard treatment for gastric cancer. Also, one of the standard treatments for cancers of the gastroesophageal junction is preoperative chemoradiotherapy, so this trial’s [data] will also influence how those cancers are managed.”

Skin/Melanoma

LBA43 - 10-y survival outcomes from the phase III CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma

Final results from the CheckMate 067 trial revealed that nivolumab given as monotherapy or in combination with ipilimumab yielded a significant and durable benefit in overall and melanoma-specific survival (MSS) at 10 years vs ipilimumab alone in patients with advanced melanoma. Data with the doublet represent the longest median OS seen in a phase 3 study of an anti–PD-1 agent for any tumor type. The median OS was 71.9 months (95% CI, 38.2-114.4) in the nivolumab plus ipilimumab arm (n = 314) vs 36.9 months (95% CI, 28.2-58.7) in the nivolumab monotherapy arm (n = 316; HR, 0.85; 95% CI, 0.69-1.05), and the HR for the doublet vs ipilimumab monotherapy (n = 315) was 0.53 (95% CI, 0.44-0.65) as the median OS with ipilimumab was 19.9 months (95% CI, 16.8-24.6).

Additionally, 10-year MSS rates were 52%, 44%, and 23% in the doublet, nivolumab monotherapy, and ipilimumab monotherapy arms, respectively.

Meredith McKean, MD, TriStar Health, Nashville, Tennessee

“In melanoma, I’m excited about the 10-year analysis of CheckMate 067. This has certainly been the landmark study in the field; [it’s] given a lot of optimism to patients and gives us our statistics to give patients hope of what we can achieve for them. I am excited to see the longest follow-up that we have to date for CheckMate 067, the landmark study of nivolumab plus ipilimumab in the frontline metastatic setting.”

LBA44 - Pembrolizumab vs ipilimumab in advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study

With 10-years of follow-up data, pembrolizumab continued to demonstrate improved survival benefits vs ipilimumab in patients with unresectable stage III or IV melanoma. Following the conclusion of the phase 3 KEYNOTE-006 study (NCT01866319) in 2019, eligible patients were able to transition to the open-label phase 3 KEYNOTE-587 extension study (NCT03486873).

The median OS among patients who received pembrolizumab (n = 556) was 32.7 months (95% CI, 24.5-41.6) vs 15.9 months (95% CI, 13.3-22.0) with ipilimumab (n = 278; HR, 0.71; 95% CI, 0.60-0.85). The 8- and 10-year OS rates were 36.9% and 34.0% in the pembrolizumab arm compared with 24.8% and 23.6% in the ipilimumab arm. Further data showed that OS was favorable in patients who received at least 94 weeks of pembrolizumab; the 8-year modified OS rate was 80.8% among these patients (n = 103). The modified median PFS with pembrolizumab was 9.4 months (95% CI, 6.7-11.6) vs 3.8 months (95% CI, 2.9-4.3) with ipilimumab (HR, 0.64; 95% CI, 0.54-0.75). Additionally, the 8- and 10-year PFS rates were 23.4% and 22.0% in the pembrolizumab arm; in the ipilimumab arm, the respective rates were 12.8% and 12.8%.

Thach-Giao Truong, MD, Cleveland Clinic, Ohio

“To me, the fact that we now have 10-year data from 2 pivotal trials, [CheckMate 067 and KEYNOTE-006], looking at the major leap forward in our fight against cancer with checkpoint inhibitors, specifically anti­–PD-1 inhibitors, is very gratifying and will trickle down to how patients with other cancers are treated. Immunotherapy is a choice for long-term, durable outcomes, and we need to start paying attention to what survivors’ [experiences are]. Our abstract discussant Jessica C. Hassel, MD, touched on that very well—what is it like to live 10 years later? At the same time, I’m also very encouraged to see that people are still looking for ways to improve [options] for patients who don’t respond to these therapies.”

LBA42 - Distant metastasis-free survival of neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in resectable, macroscopic stage III melanoma: The NADINA trial

Neoadjuvant ipilimumab plus nivolumab bested adjuvant nivolumab in patients with resectable, macroscopic stage III melanoma, according to updated findings from the phase 3 NADINA trial (NCT04949113). At a median follow-up of 15.4 months (95% CI, 9.0-22.4), patients in the neoadjuvant arm (n = 212) experienced an 18-month EFS rate of 80.8% vs 53.9% in the adjuvant arm (n = 211; adjusted HR, 0.32; 95% CI, 0.22-0.48; nominal P < .001). Neoadjuvant therapy consisted of 2 courses of combination therapy with 80 mg of ipilimumab and 240 mg of nivolumab given every 3 weeks.

Further, the 18-month distant metastasis-free survival (DMFS) rates were 85.7% vs 62.4%, respectively (adjusted HR, 0.37; 95% CI, 0.24-0.57; nominal P < .001). In the neoadjuvant arm, the final radiological response rate was 37.2%, which consisted of a 12.7% CR rate; the final pathological response rate was 68.8%, consisting of a 49.1% CR rate. Investigators also noted that patients in the neoadjuvant arm who had a major pathologic response or a radiological response experienced favorable recurrence-free survival and DMFS rates at 18 months.

Piotr Rutkowski, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

“From my point of view, the presentation of the NADINA trial on preoperative therapy [was notable, as it was the] first time DMFS data have been published, [and there was] amazing [efficacy seen] compared with the standard adjuvant therapy. Taking into account that the treatment is only 2 cycles of preoperative therapy with such meaningful efficacy—[there was] more than a 20% difference between the standard arm with adjuvant therapy and preoperative treatment [arm in DMFS]—that should be a new SOC in patients with palpable nodal metastasis.”