Sabrina Serani

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.

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Articles

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.


Targeted Chemo Improves Survival in Early-Stage Lung Cancer

Nubeqa/ADT treatment led to positive impacts on HRQoL vs placebo in mHSPC: © stock.adobe.com.

Among patients with with metastatic hormone-sensitive prostate cancer (mHSPC), Nubeqa (darolutamide) and androgen deprivation therapy (ADT) treatment led to positive impacts on health-related quality of life (HRQoL) when compared with placebo and ADT, according to patient-reported outcome data from the phase 3 ARANOTE trial.

Notably, these data, which were shared at the

, also highlighted clinically meaningful delays in pain progression with the investigative treatment.

Furthermore, on June 3rd, 2025, just days after the data was presented at the meeting, the United States Food and Drug Administration 

(FDA) granted approval to Nubeqa for the treatment of patients

 with mHSPC based on data from the ARANOTE study.

“[This] is the first and only androgen receptor antagonist to demonstrate clinically meaningful delays in pain progression and overall well-being, including those specific areas of social and family well-being, functional well-being, and urinary symptoms. Health-related quality of life benefits may be greatest in patients treated with Nubeqa who had ultralow [prostate-specific antigen (PSA)] levels,” explained Dr. Alicia Morgans, in a presentation of the study

Morgans, a genitourinary medical oncologist who serves as the director of the Survivorship Program at Dana-Farber Cancer Center and associate professor of Medicine at Harvard Medical School, in Boston.

In this analysis, multiple patient-reported outcome measures were used to assess patient experience during treatment. They included the Brief Pain Inventory Short Form (BPI-SF), used to assess pain, specifically the worst pain in the past 24 hours, and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, a questionnaire evaluating overall quality of life in patients with prostate cancer. The FACT-P includes domains such as physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer-specific assessments, including bowel and urinary difficulties.

The analysis showed that Nubeqa was associated with a delay in pain progression, defined as the time from randomization to a confirmed increase of at least 2 points in worst pain over the nadir or the initiation of opioid treatment for at least 7 days versus placebo. When assessing time to pain progression by PSA response, patients who reached a PSA of less than 0.02 or 0.2 nanograms per millilitre (ng/mL) at any time had a longer time to pain progression than patients with a PSA greater than or equal to 0.2 ng/mL.

“I think this is a critical thing for us to recognize that our patients’ quality of life, intuitively, of course, is associated with disease control. But this is also helpful for us in clinical practice so that we can encourage patients as their cancer appears to be better controlled; we expect them to feel better,” Morgans explained during the presentation.

Regarding time to FACT-P deterioration, Nubeqa was associated with an extension in median time to deterioration, defined as the first decrease of 10 or more points in the total score, by 5.1 months versus placebo. Improvements were most prominent in the areas of social and family well-being, functional well-being, and prostate cancer concerns, including urinary symptoms. Similarly with the BPI-SF, patients with a PSA of 0.02 or 0.2 ng/mL at any time had a longer time to HRQoL deterioration versus a PSA of 0.2 ng/mL or greater.

The phase 3 ARANOTE trial assessed Nubeqa plus ADT versus placebo and ADT for the treatment of mHSPC. 

2024 European Society of Medical Oncology (ESMO) Congress

 showed that the combination reduced the risk of radiographical progression or death by 46% and demonstrated a favorable safety profile.

 for the study combination in patients with mHSPC in November, 2024.

the 2025 ASCO Genitourinary Cancers Symposium

A total of 669 patients enrolled globally were randomly assigned on a 2:1 basis to receive Nubeqa 600 mg twice daily plus ADT (446 patients) or placebo plus ADT (223 patients). The primary end point was radiographic progression-free survival by central blinded review, with secondary end points including overall survival, time to PSA progression, and safety.

At a data cutoff of June 7, 2024, the median follow-up was 25.3 months for the Nubeqa group and 25.0 months for the placebo group. The median radiographic progression-free survival for Nubeqa plus ADT was not reached compared with 25.0 months for placebo plus. At 24 months, the rate of radiographic progression-free survival was 70.3% for the Nubeqa group versus 52.1% for the placebo group.

The median treatment duration was 24.2 months in the Nubeqa group compared with 17.3 months for the placebo group. Incidence of treatment-emergent side effects was similar between the arms, with 91.0% any-grade and 30.8% grade 3 (severe) or 4 (life-threatening) treatment-emergent side effects with Nubeqa plus ADT and 90.0% any-grade and 30.3% grade 3 or 4 with ADT plus placebo.

“Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial” by Dr. Moregans, et al. 

Nubeqa (darolutamide) combined with androgen deprivation therapy (ADT) significantly improved health-related quality of life (HRQoL) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to placebo and ADT, as demonstrated in the phase 3 ARANOTE trial. The treatment delayed pain progression and was associated with better social, family, and functional well-being. Following these findings, the FDA approved Nubeqa for mHSPC. The trial also showed a 46% reduction in radiographic progression or death risk, with a favorable safety profile and extended radiographic progression-free survival.

Nubeqa and ADT treatment led to positive impacts on health-related quality of life vs placebo in metastatic hormone-sensitive prostate cancer. 

Nubeqa Combo Positively Impacts HRQoL vs Placebo in Prostate Cancer Subgroup 

Treatment with Herceptin (trastuzumab) and Perjeta (pertuzumab) with endocrine therapy but without chemotherapy has been shown to potentially be an effective treatment for patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer. Furthermore, the addition of Kisqali (ribociclib) might improve patient outcomes even more.

These findings come from the second interim efficacy analysis of the phase 3 DETECT V trial presented at the 2024 ESMO Congress.

In the study, 270 patients with metastatic HR/HER2–positive breast cancer receiving a first to third line of treatment were randomized to one of two arms. In the chemotherapy arm, patients received physician’s choice of chemotherapy plus Herceptin/Perjeta followed by maintenance Herceptin/Perjeta and endocrine therapy. In the chemotherapy-free arm, patients received physician’s choice of endocrine therapy plus Herceptin/Perjeta. After 124 patients enrolled, the study was amended to add Kisqali to endocrine therapy in both arms. 

The combination of Herceptin, Perjeta, and endocrine therapy without chemotherapy showed promising results in patients with HR+/HER2+ metastatic breast cancer.

Adding Kisqali to the treatment regimen further improved patient outcomes, reducing the risk of disease progression or death.

The DETECT V trial suggests that a chemotherapy-free regimen with Herceptin, Perjeta, and endocrine therapy, potentially with the addition of Kisqali, may be a promising treatment option for patients with HR+/HER2+ metastatic breast cancer.

Overall survival (OS, the time a patient lives, regardless of disease status) and progression-free survival (PFS, the time a patient lives without their disease spreading or worsening) was similar between the arms. In the chemotherapy-free arm, the median OS was not reached (meaning more than half of the patients in that arm were still alive) versus 46.1 months in the chemotherapy arm. For PFS, the median was 19.1 months in the chemotherapy-free arm versus 22.4 months in the chemotherapy arm.

The addition of Kisqali improved PFS and OS, with patients treated with Kisqali being 48% less likely to experience disease progression or death and being 58% less likely to die of any cause.

Dr. Wolfgang Janni emphasized that this was a comparison of subsequent study cohorts, not a randomized comparison for the addition of Kisqali. Janni is a professor at the University of Ulm in Ulm, Germany.

Regarding safety of the chemotherapy versus chemotherapy-free arms, the most common side effect in both arms was diarrhea, with 100 all-grade incidences in the chemotherapy-free arm and 146 in the chemotherapy arm.

“We did observe a higher amount of diarrhea in the chemotherapy containing arm, while we saw more prolonged neutropenia [low count of neutrophils, a type of white blood cell] in the chemo[therapy]-free arm, possibly due to longer exposure to [Kisqali],” Janni explained. In the chemotherapy-free arm, there were 64 incidences of all-grade neutropenia and 48 grade 3 (severe) or higher.

For the safety analysis of Kisqali versus no Kisqali, 55 patients (37.4%) receiving Kisqali experienced at least one serious side effect versus 43 patients (34.7%) in the no Kisqali arm. Ninety-five patients (64.6%) and 62 patients (50%) in the Kisqali and no Kisqali arms, respectively, experienced at least one grade 3 or higher side effect.

“The tolerability comparison between the two cohorts did not show a difference in the overall incidence of serious [side effects], but in [side effects] with grade 3 or higher, which was mainly caused by the higher incidence of neutropenia and liver enzyme abnormalities in the [Kisqali] cohort. There were no treatment-associated deaths in this study,” Janni said.

The final results from this study are pending, as are longer-term findings from the Kisqali cohort, which had shorter follow-up due to its later addition into the study regimens.

Among patients with HR+/HER2+ breast cancer, Herceptin and Perjeta plus endocrine therapy proved to be beneficial without chemotherapy.

Herceptin, Perjeta Regimen May Be Effective Without Chemo in Breast Cancer

A treatment combination of Imjudo (tremelimumab) and Imfinzi (durvalumab) demonstrated improved survival outcomes, including disease control and treatment responses in patients with unresectable (surgically unremovable) hepatocellular carcinoma (liver cancer), according to a presentation at the 

The presentation highlighted updated five-year data from the phase 3 HIMALAYA study. These results set new standards in unresectable liver cancer, with one in 5 patients alive at five years, Dr. Lorenza Rimassa said in the presentation. 

A combination treatment of Imjudo (tremelimumab) and Imfinzi (durvalumab) has shown improved survival outcomes in patients with unresectable liver cancer.

The phase 3 HIMALAYA study revealed that one in five patients treated with Imjudo plus Imfinzi were alive at five years, surpassing the 9.4% survival rate for those treated with Nexavar.

Patients in the Imjudo plus Imfinzi group experienced a median overall survival of 16.43 months compared to 13.77 months in the Nexavar group.

The Imjudo plus Imfinzi combination also demonstrated better disease control, with higher rates of complete and partial responses and lower rates of disease progression.

Rimassa is an associate professor of medical oncology at Humanitas University and head of the Hepatopancreatobiliary Oncology Department at Istituto di Ricovero e Cura a Carattere Scientifico Maugeri Humanitas Research Hospital in Milan, Italy.

“This five-year updated analysis of the HIMALAYA study presents the longest follow-up to date in phase 3 studies for [unresectable liver cancer],” Rimassa said. “[Imjudo plus Imfinzi] sustained an overall survival (OS; time patients live, regardless of disease status) benefit versus [Nexavar (Nexavar)] and demonstrated unprecedented long-term survival benefit at five years, with a five-year survival rate of 19.6% for [Imjudo plus Imfinzi] versus 9.4% for [Nexavar].”

Survival Benefits of Imjudo Plus Imfinzi Versus Nexavar in Unresectable Liver Cancer

A total of 1,171 patients were randomly assigned to three treatment groups. The Imjudo-Imfinzi combination group included 393 patients. There were 389 patients in the Imfinzi monotherapy group and patients 389 patients in the Nexavar group. In the study, 393 patients were treated with the Imjudo-Imfinzi combination and 389 patients received Nexavar.

Patients from the Imjudo-Imfinzi combination group compared with Nexavar sustained an OS benefit. Specifically, the median OS was 16.43 months in the combination group and 13.77 in the Nexavar group. The median follow-up duration was 62.49 versus 59.86 months, respectively.

For patients experiencing disease control, the OS was enhanced, showing rates of 28.7% in the Imjudo-Imfinzi combination group and 12.7% in the Nexavar group at five years and increasing over time. There were 12 patients (3.1%) in the Imjudo-Imfinzi combination group who achieved complete response (disappearance of cancer) versus no patients in the Nexavar group, and 67 patients (17.0%) experienced partial response (tumor shrinkage) versus 20 patients (5.1%), respectively. Stable disease was achieved by 157 (39.9%) in the Imjudo-Imfinzi combination group and 216 patients (55.5%) in the Nexavar group, and 141 patients (35.9%) versus 118 (30.3%), respectively, experienced disease progression.

“More patients treated with [Imjudo-Imfinzi combination] versus Nexavar were still alive, still on study treatment, and fewer received a subsequent therapy at five years,” Rimassa noted.

Patients receiving the Imjudo-Imfinzi combination also experienced deeper tumor responses, including over 50% shrinkage in 34 patients, which was associated with longer overall survival, compared with 12 patients receiving Nexavar. In addition, 80 patients in the Imjudo-Imfinzi combination group versus 114 patients in the Nexavar group experienced minor responses of less than 30% tumor shrinkage; however, this also led to a long-term survival benefit for those receiving Imjudo-Imfinzi combination. In the Imjudo-Imfinzi combination group, there were 168 patients who had no shrinkage or growth versus 169 patients in the Nexavar group.

Rimassa stated that there were no new serious treatment-related side effects after the primary analysis with a data cut-off on Aug. 27, 2023. At the five-year data cut-off of March 1, 2024, 17.5% of patients in the Imjudo-Imfinzi combination group had experienced serious treatment-related side effects, which was the same percentage reported at the primary analysis. Similarly, for the Nexavar group, at the five-year analysis at the data cut-off, there were 9.9% of patients who experienced serious treatment-related side effects versus 9.4% at the primary data cut-off.

There were also 24.8% of patients in the Imjudo-Imfinzi combination group that had serious non-treatment-related side effects at the five-year data cut-off versus 23% at the primary data cut-off, and in the Nexavar group, there were 20.3% of patients experiencing serious non- treatment-related side effects versus 20.3%, respectively.

“Overall survival benefit with [the Imjudo-Imfinzi combination] was enhanced in patients who achieved disease control. Any degree of tumor shrinkage was linked to long-term survival, with those experiencing deep responses showing the greatest benefit. These findings indicate that conventional response measures such as complete response or partial response … may not fully capture the benefits of [the Imjudo-Imfinzi combination],” Rimassa concluded.

In patients with unresectable liver cancer, treatment with Imjudo plus Imfinzi showed better survival outcomes compared with Nexavar.

Sabrina Serani

Targeted Chemo Improves Survival in Early-Stage Lung Cancer

Nubeqa Combo Positively Impacts HRQoL vs Placebo in Prostate Cancer Subgroup

Herceptin, Perjeta Regimen May Be Effective Without Chemo in Breast Cancer

Imjudo Plus Imfinzi Improve Survival Versus Nexavar in Liver Cancer

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