Ariana Pelosci

Columvi combo enhances survival outcomes vs Rituxan combo in R/R DLBCL: © stock.adobe.com.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), Columvi (glofitamab) plus chemotherapy with gemcitabine and oxaliplatin (GemOx) demonstrated enhanced survival outcomes compared with Rituxan (rituximab) plus GemOx, according to a two-year follow-up data from the phase 3 STARGLO trial presented at the 

Efficacy data from the trial revealed that after a median follow-up of 24.7 months, Columvi plus GemOx exhibited superior overall survival versus Rituxan/GemOx; the median overall survival was not evaluable versus 13.5 months. Additionally, the 24-month overall survival rate in each arm was 54.4% versus 33.6%. The median progression-free survival in each arm was 13.8 months versus 3.6 months, with respective 18-month progression-free survival rates of 46.5% versus 23.0%.

The objective response rates in the Columvi and Rituxan arms were 68.3% versus 40.7%. Furthermore, the complete response rate with Columvi was 58.5% versus 25.3% with Rituxan. Among responders to Columvi, the median duration of complete response was not reached versus 24.2 months for responders to Rituxan. A total of 42.1% of the Columvi arm and 17.6% of the Rituxan arm had an ongoing complete response at data cut-off.

Following the end of treatment, the median overall survival and progression-free survival was not estimable in the Columvi arm. The respective 12-month overall survival and progression-free survival rates were 89.3% and 82.4%.

“With 2-year follow-up data of the [phase 3] STARGLO trial, Columvi/GemOx continues to show a sustained benefit in overall survival, progression-free survival, and response compared to [Rituxan]/GemOx,” Dr. Jeremy S. Abramson, director of the Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital and a professor of Medicine at Harvard Medical School, said in the presentation. “We saw that more than half of patients remain alive after Columvi/GemOx, and the majority of responders were not only alive, but progression-free.”

Patients in the phase 3 trial were randomly assigned to receive Columvi plus GemOx (183 patients) or Rituxan plus GemOx (91 patients). Those in the Columvi arm received step-up dosing in cycle one, then a 30 milligram (mg) target dose every 31 days starting cycle two, day one. Patients were given eight cycles of Columvi with GemOx followed by four cycles of Columvi as monotherapy.

In the Rituxan and Columvi arms, respectively, the median age was 69.0 years (range, 20-84) versus 68.0 years (range, 22-88), 58.2% versus 57.4% of patients were male, and 56.0% versus 47.0% were Asian. A total of 62.6% versus 62.8% had one prior line of therapy, 51.6% versus 57.9% were primary refractory to last treatment, and 90.9% versus 88.9% had an ECOG performance status of zero or one. Furthermore, 77.8% versus 66.7% had Ann Arbor stage 3 or 4 disease, 15.6% versus 12.6% had bulky disease of 10 centimeter or greater, and 8.8% versus 7.7% received prior CAR-T cell therapy.

The primary end point of the trial was overall survival. Secondary end points included independent review committee–assessed progression-free survival and complete response rates, with a landmark analysis of patients with complete responses at end of treatment performed.

Among those treated with Rituxan and Columvi, 17.0% versus 52.3% experienced serious side effects. Furthermore, 40.9% versus 76.7% experienced grade 3 (serious) or higher side effects, including 4.5% versus 7.0% of patients on each respective arm dying. Side effects leading to treatment discontinuation occurred in 12.5% and 25.6% of the Rituxan and Columvi arms.

In the Columvi arm, the incidence of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was 44.8% and 2.3%, with respective grade 3/4 rates of 2.3% and 0.6%. Infections of any grade occurred in 29.5% and 55.2% of the Rituxan and Columvi arms, respectively, with 9.1% and 16.9% of patients experiencing grade 3 (serious)/4 (life-threatening) infections, and 3.4% versus 3.5% dying from infections.

"Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO" by Dr. Jeremy S. Abramson, et al. American Society of Clinical Oncology Annual Meeting.

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Articles

Columvi plus chemo had enhanced survival outcomes vs Rituxan plus chemo in patients with relapsed/refractory diffuse large B-cell lymphoma. 

Columvi Combo Enhances Survival Outcomes in R/R Lymphoma Subgroup 

The COCOON dermatologic management regimen reduced QOL  impact of Rybrevant/Lazcluze vs SOC in EGFR-mutated NSCLC: © stock.adobe.com.

The COCOON dermatologic management regimen significantly reduced the quality-of-life impact associated with Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) treatment versus the standard-of-care dermatologic management approach in patients with EGFR-mutated non-small cell lung cancer (NSCLC), according to phase 2 findings from the COCOON trial, which were shared at the 

A lower average Skindex-16 total score was reported in patients who received COCOON DM versus those with standard-of-care dermatologic management at day 15 of cycle three. Additionally, use of COCOON DM correlated with improvements in the functioning, emotional and symptoms subscales.

No moderate or severe symptoms on the Patient Global Impression of Severity (PGI-S) scale occurred among patients who received COCOON DM at day 15 of cycle three. The rates of patients reporting no symptoms in the COCOON DM and standard-of-care dermatologic management arms, respectively, were 21% versus 7% for rash, 23% versus 7% for skin conditions and 27% versus 16% for nail infections.

“At this analysis, which evaluated the first 12 weeks of treatment, [patients] in the COCOON DM arm experienced lower severity of dermatologic symptoms and a reduced impact on quality of life than [patients] in the standard-of-care dermatologic management arm,” lead study author Jill Feldman, founder of EGFR Registers, a patient advocacy group in Deerfield, Illinois, wrote with coauthors. “Substantial and consistent separation favoring COCCON DM was observed in all postbaseline Skindex-16 subscales. Most [patients] in the COCOON DM arm reported mild or no dermatologic symptoms. This benefit was consistently observed across the first [approximately] 10 weeks of treatment.”

Investigators of the phase 2 COCOON trial prospectively assessed a novel DM regimen for preventing moderate to severe EGFR-associated side effects that may occur following treatment with amivantamab plus lazertinib. In this analysis, investigators highlighted patient-reported outcomes from the first 12 weeks of therapy.

A total of 201 patients were randomly assigned to receive amivantamab/lazertinib plus COCOON DM (99 patients) or standard-of-care dermatologic management (102 patients). The COCOON regimen consisted of oral doxycycline or minocycline for 12 weeks followed by topical clindamycin lotion each day on the scalp, starting at week 13 for nine months; chlorhexidine on the nails each day for 12 months; and ceramide-based moisturizer applied to the body and face at least each day for 12 months. In the standard-of-care dermatologic management arm, patients received general skin prophylaxis based on local practice and relative treatment, including corticosteroids and systemic antibiotics.

The study’s primary end point was the incidence of grade 2 or higher dermatologic side effects within the first 12 weeks following the beginning of amivantamab/lazertinib therapy. The select secondary end points were PROs per Skindex-16 and PGI-S after 12 weeks of follow-up.

The Skindex-16 questionnaire was validated to determine how skin conditions impact quality of life based on the subscales of functioning, emotional, and symptoms. The PGI-S was a patient-reported 4-point rating scale — none, mild, moderate, or severe symptoms — used to evaluate the severity of rashes, skin conditions, and nail infections over time.

Those with locally advanced or metastatic, treatment-naïve NSCLC harboring documented EGFR exon 19 deletions or 

 mutations were eligible for enrollment on the study. An ECOG performance status of 0 or 1 was an additional requirement for study entry.

 for patients with locally advanced or metastatic EGFR

mutated NSCLC based on findings from the phase 3 MARIPOSA trial.

“Dermatologic prophylaxis and impact on patient-reported outcomes in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Results from the phase 2 COCOON trial” by Dr. J. Feldman, et al., 2025 ASCO Annual Meeting.

The COCOON trial demonstrated that the COCOON dermatologic management regimen significantly improved quality of life for patients with EGFR-mutated NSCLC treated with amivantamab and lazertinib, compared to standard dermatologic care. Patients receiving COCOON DM reported lower Skindex-16 scores, indicating better functioning, emotional well-being, and fewer symptoms. No moderate or severe symptoms were observed on the PGI-S scale in the COCOON DM group. The trial involved 201 patients and highlighted the regimen's effectiveness in reducing dermatologic side effects, with substantial benefits observed within the first 12 weeks of treatment.

The COCOON dermatologic management regimen reduced the quality-of-life impact of Rybrevant/Lazcluze vs SOC treatment in patients with EGFR-mutated NSCLC. 

COCOON Regimen Eases Dermatologic Side Effects After Treatment in EGFR+ NSCLC

Imlunestrant alone or in combination with Verzenios improved patient-reported outcomes in ER+, HER2– advanced breast cancer following endocrine therapy: © stock.adobe.com.

Imlunestrant alone or in combination with Verzenios (abemaciclib) improved patient-reported outcomes among those with with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer who progressed after endocrine therapy.

Notably, these data were derived from the phase 3 EMBER-3 trial presented at the 2025 ASCO Annual Meeting. In patients with an ESR1 mutation, based on changes in baseline in the EORTC QLQ-C30 global health status/quality of life score, treatment with imlunestrant was favored compared with standard of care endocrine therapy. At treatment cycle seven, the difference between groups was 9.9 points. The global health status/quality of life score was typically maintained across both treatment arms.

In patients with an ESR1 mutation, the median time to deterioration of global health status/quality of life score with imlunestrant was 5.6 months, with 53 events, compared with 3.8 months and 50 events, with endocrine therapy. The investigators noted that estimates were limited by a high rate of censoring.

Additionally, in patients with an ESR1 mutation, overall global health status/quality of life score and functional domains remained consistent. Imlunestrant was superior regarding the physical, role, social, emotional, and cognitive functional domains. Regarding symptom domains, worse scores were observed with endocrine therapy for fatigue, pain, dyspnea, insomnia and appetite loss; worse scores were observed with imlunestrant for nausea/vomiting, constipation, and diarrhea. It was noted that symptom domains were broadly similar between treatment groups.

In all patients, the overall changes in global health status/quality of life score and functional domains were typically maintained across all treatment arms. In order from worst to best, the mean change from baseline for global health status/quality of life score was imlunestrant plus Verzenios, endocrine therapy and imlunestrant; for physical function, social function, emotional function and cognitive function, it was the same, and for role function, it was endocrine therapy, imlunestrant plus Verzenios, and imlunestrant.

Regarding symptom domains, imlunestrant plus Verzenios demonstrated clinically meaningful worse scores regarding nausea/vomiting and diarrhea. The average proportion of time with “frequent” or “almost constant” diarrhea was 22% with imlunestrant plus Verzenios, 3% with imlunestrant, and 2% with endocrine therapy.

“Consistent with the primary results from EMBER-3, these patient-reported outcomes results reinforce the benefit of imlunestrant, as monotherapy or combined with Verzenios, as an all-oral targeted therapy option after progression on [endocrine therapy] for patients with ER-positive, HER2-negative [advanced breast cancer],” wrote lead study author Dr. Giuseppe Curigliano, a professor of medical oncology at the University of Milano, and of the European Institute of Oncology, National Institute of Hospitalization and Scientific Care in Milano, Italy, and coauthors, in the presentation.

The trial enrolled approximately 859 patients who were randomly assigned to receive either imlunestrant monotherapy (327 patients), imlunestrant plus Verzenios (208 patients) or endocrine therapy (324 patients). Imlunestrant was given at 400 milligrams (mg) every day in both groups; Verzenios was given at the labeled dose; and endocrine therapy, which was the investigator’s choice between Faslodex (fulvestrant) or Aromasin (exemestane), was also given at the labeled dose.

Eligible patients had ER-positive, HER2-negative advanced disease. Regarding prior therapies, in the adjuvant setting, patients had recurrence on or within 12 months of completion of an aromatase inhibitor with or without a CDK4/6 inhibitor; for advanced breast cancer, patients had progression on a first-line aromatase inhibitor with or without a CDK4/6 inhibitor and no other therapy for advanced breast cancer.

The trial’s primary end points were investigator-assessed progression-free survival across all treatment groups. Secondary end points included overall survival, blinded independent committee review-assessed PFS, overall response rate, and safety; exploratory end points were patient-reported outcomes.

The patient-reported outcomes measures used and their respective schedules are as follows: the EORTC QLQ-C30 global health status/quality of life score, function domains, and symptom domains were assessed on day one and then every eight weeks after with short-term follow-up; the EORTC IL-19 physical functioning was assessed every eight weeks opposite the EORTC QLQ-C30; the Patient-reported Outcomes version of the Common Terminology Criteria for Adverse Events (a patient-reported outcome measurement system developed by the National Cancer Institute to capture symptomatic adverse events in patients on cancer clinical trials; PRO-CTCAE) for frequency of diarrhea was assessed on day one then every week after with short-term follow-up; and the PRO-CTCAE injection site reaction occurrence was assessed every week of cycle one then the first two weeks of all other cycles.

It was reported that 72% of patients receiving Faslodex experienced injection site reaction at any time of treatment; 20% of them had an incidence of less than 25%, 32% had an incidence from 25% to 50%, 30% had an incidence from 50% to 75%, and 17% had an incidence of greater than 75%.

The median investigator-assessed progression-free survival, in all patients, was 9.4 months with imlunestrant plus Verzenios and 5.5 months with imlunestrant alone. In patients with an ESR1 mutation, the median progression-free survival was 5.5 months with imlunestrant alone versus 3.8 months with endocrine therapy.

Regarding safety, treatment-emergent side effects of any grade occurred in 83% of patients with imlunestrant, 98% of patients with imlunestrant plus Verzenios, and 84% of patients with endocrine therapy; of grade 3 or higher, treatment-emergent side effects occurred in 17%, 49%, and 21%, respectively.

In patients with imlunestrant, dose reductions, treatment discontinuations, and death due to side effects occurred in 2%, 4%, and 2%; in patients with imlunestrant plus Verzenios, they occurred in 39%, 6%, and 1%, respectively; and in patients with endocrine therapy, they occurred in 0%, 1%, and 1%.

“Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial" by Dr. Curigliano G, et al., 

Imlunestrant, alone or with Verzenios (abemaciclib), improved patient-reported outcomes in ER-positive, HER2-negative advanced breast cancer patients post-endocrine therapy. The phase 3 EMBER-3 trial showed that imlunestrant was favored over standard endocrine therapy, particularly in patients with an ESR1 mutation, with better global health status/quality of life scores. Imlunestrant demonstrated superiority in functional domains, though symptom domains varied between treatments. The trial's primary endpoint was progression-free survival, with imlunestrant plus Verzenios showing a median of 9.4 months compared to 5.5 months with imlunestrant alone.

Imlunestrant alone or in combination with Verzenios improved patient-reported outcomes in ER+, HER2– advanced breast cancer following endocrine therapy. 

Imlunestrant Alone or With Verzenios Improved PROs in Advanced Breast Cancer

Enhertu plus Perjeta improved progression-free survival to 40.7 months versus 26.9 months with standard care in advanced HER2-positive breast cancer.

Enhertu (fam-trastuzumab deruxtecan-nxki; T-DXd) combined with Perjeta (pertuzumab) as first-line treatment improved progression-free survival (PFS) versus standard care for patients with HER2-positive advanced or metastatic breast cancer, according to findings from the phase 3 DESTINY-Breast09 trial presented in a press briefing at the 

Data showed a median PFS of 40.7 months with Enhertu plus Perjeta versus 26.9 months with a taxane plus trastuzumab (Herceptin) and Perjeta. In the Enhertu and THP arms, respectively, the PFS rates were 93% versus 87.8% at 6 months, 85.9% versus 72.4% at 12 months and 70.1% versus 52.1% at 24 months.

As of the data cutoff of February 26, 2025, data were immature.

“The combination of [Enhertu and Perjeta] demonstrated a statistically significant and clinically meaningful improvement in PFS compared with THP,” lead study author Dr. Sara M. Tolaney, chief of the division of Breast Oncology at Dana-Farber Cancer Institute, in Boston, Massachusetts, stated during the press briefing. “These data suggest that the combination of [Enhertu and Perjeta] may represent a new first-line standard of care for patients with metastatic HER2-positive breast cancer.”

Progression-free survival (PFS): time during and after treatment that a patient lives without cancer growing or spreading.

Duration of response (DOR): length of time a treatment keeps cancer under control after it first responds.

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

De novo disease: cancer that is already advanced or metastatic at the time of diagnosis, rather than recurring after earlier treatment.

PIK3CA mutation: a genetic alteration found in some cancers that may affect how the disease behaves or responds to treatment.

ECOG performance status: a scale used to assess how a patient’s disease affects their daily living abilities, ranging from fully active (0) to completely disabled (5).

According to Tolaney, the PFS benefit with the Enhertu regimen extended across all subgroups, which included patients regardless of de novo or recurrent disease, hormone receptor status, and PIK3CA mutation status. Additionally, the median duration of response (DOR) was 39 months with the Enhertu combination, with complete responses reported in 15.1% and 8.5% of the investigational and comparator arm, respectively. Tolaney also noted that early overall survival (OS) data highlighted a trend towards improved outcomes with Enhertu plus Perjeta.

The safety profile of Enhertu plus Perjeta in the DESTINY-Breast09 trial was comparable to prior reports of each individual agent. Any-grade treatment-emergent adverse effects (TEAEs) in the Enhertu and THP arms, respectively, included nausea (71.1% versus 28.8%), diarrhea (55.9% versus 54.2%), neutropenia (48.8% versus 44.5%) and fatigue (48.3% versus 34.6%). Additionally, the most common grade 3 (severe) or higher TEAEs in each arm included neutropenia (23.9% versus 33.2%), hypokalemia (10.2% versus 1.6%) and anemia (8.4% versus 3.7%).

In the multicenter, open-label DESTINY-Breast09 study, patients with HER2-positive metastatic or advanced breast cancer were randomly assigned 1:1:1 to receive Enhertu at 5.4 milligram per kilogram (mg/kg) every three weeks plus placebo (387 patients), Enhertu plus Perjeta (383 patients), or a taxane consisting of paclitaxel or docetaxel in combination with trastuzumab and Perjeta (387 patients). Tolaney noted that outcomes in the Enhertu plus placebo arm would remain blinded until the time of the final PFS analysis.

The trial’s primary end point was PFS per blinded independent central review. A key secondary end point was OS. Other secondary end points included PFS per investigator evaluation, objective response rate, DOR and safety and tolerability.

Patients 18 years and older with pathologically documented advanced or metastatic HER2-positive breast cancer, and no prior chemotherapy or HER2-targeted agents for advanced or metastatic disease, or only 1 prior line of endocrine therapy in the metastatic setting, were eligible for enrollment on the trial. Other requirements for study entry included having adequate organ and bone marrow function and an ECOG performance status of 0 or 1. Investigators stratified patients by whether they had de novo or recurrent disease, hormone receptor — positive or hormone receptor — negative disease and detected or non-detected PIK3CA mutations.

“Trastuzumab deruxtecan plus Perjeta versus standard therapy for first-line HER2-positive advanced breast cancer” by Dr. Sara Tolaney, et al., 

Enhertu combined with Perjeta as a first-line treatment significantly improved progression-free survival (PFS) in HER2-positive advanced or metastatic breast cancer compared to standard care, as demonstrated in the DESTINY-Breast09 trial. The combination showed a median PFS of 40.7 months versus 26.9 months with the standard regimen. The PFS benefit was consistent across various subgroups, and the safety profile was comparable to previous reports. The trial's primary endpoint was PFS, with secondary endpoints including overall survival, objective response rate, and safety.

Adding Enhertu to Perjeta improved time without cancer growth versus standard care in advanced HER2-positive breast cancer, as per data from DESTINY-Breast09.

Ariana Pelosci

Columvi Combo Enhances Survival Outcomes in R/R Lymphoma Subgroup

COCOON Regimen Eases Dermatologic Side Effects After Treatment in EGFR+ NSCLC

Imlunestrant Alone or With Verzenios Improved PROs in Advanced Breast Cancer

Initial Enhertu Combo Improves Survival in HER2+ Advanced Breast Cancer

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