Russ Conroy

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.

Feldman J, et al. “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.” 

 2025;43(suppl 16):8641. doi:10.1200/JCO.2025.43.16_suppl.8641

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Articles

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

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.

Initial Enhertu Combo Improves Survival in HER2+ Advanced Breast Cancer

Neoadjuvant chemotherapy plus chemoradiation was safe and effective for long-term bladder preservation in select patients with muscle-invasive bladder cancer.

Among patients with nonmetastatic, muscle-invasive bladder cancer (MIBC), treatment with neoadjuvant cisplatin-based combination chemotherapy (NAC) plus bladder-saving concurrent chemoradiation therapy was effective and safe in the long term, according to findings presented at the 2025 ASCO Genitourinary Cancers Symposium.

Efficacy data revealed that after a median follow-up of 96 months, the median disease-free survival (DFS) in patients treated with NAC followed by CRT for nonmetastatic MIBC was 56.6 months, with a five-year DFS rate of 49.2%. Furthermore, the median bladder intact DFS (BI-DFS) in this patient group was 45.6 months, and the five-year BI-DFS was 47.6%. Additionally, the median overall survival (OS) was 105 months with a five-year OS rate of 62.2%.

“[Neoadjuvant, cisplatin-based chemotherapy plus] concurrent chemoradiotherapy is a safe and effective bladder-sparing approach with encouraging long-term outcomes in carefully selected patients with MIBC,” Dr. Meghan E. Mahoney of the Division of Medical Oncology at the Tom Baker Cancer Centre in Calgary, Alberta, Canada, wrote in the presentation with study coinvestigators.

The study investigators contextualized the study background by highlighting a paucity of long-term data on the efficacy and tolerability of trimodality therapy in patients with MIBC opting for bladder-sparing approaches.

Neoadjuvant: administered prior to the primary treatment, such as surgery.

Disease-free survival: the time after treatment that a patient lives without signs or symptoms of cancer.

Overall survival: the time that a patient lives, regardless of disease stats.

Maximal transurethral resection of a bladder tumor: the removal of a tumor through the urethra.

Cystoscopy: a procedure to examine the bladder and urethra.

Radical cystectomy: surgical removal of the bladder.

ECOG performance status: a way to measure patients’ ability to complete daily tasks, with a lower number indicating greater independence.

Hydronephrosis: when the kidney becomes swollen due to a buildup of urine.

A total of 56 patients with nonmetastatic MIBC who were given NAC followed by bladder-sparing CRT between 2008 and 2017 at the Princess Margaret and Durham Regional Cancer Centers were included in the retrospective chart review. The primary outcomes were five-year DFS, BI-DFS and OS.

Patients initially underwent maximal transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant treatment with gemcitabine plus cisplatin for two to four cycles. Following the second cycle of neoadjuvant treatment, imaging occurred in all patients, and those experiencing disease progression underwent cystoscopy before undergoing immediate radical cystectomy plus lymph node dissection. Furthermore, following the fourth cycle, all patients underwent imaging and cystoscopy, and those who experienced disease progression underwent maximal re-TURBT before undergoing immediate radical cystectomy plus lymph node dissection.

Responders to neoadjuvant treatment and those with stable disease were treated with external beam radiation therapy (EBRT) at a dose of 60 to 66 Gy to the bladder and pelvic lymph nodes, as well as concurrent weekly cisplatin at 40 mg/m

 for six weeks. Surveillance cystoscopy, imaging and urine cytology occurred after CRT every three to four months.

During the surveillance period, those with no recurrence continued surveillance. Additionally, those with non-MIBC recurrence repeated TURBT with or without Bacillus Calmette-Guerin treatment. Those with MIBC recurrence underwent salvage cystectomy. Furthermore, patients who experienced distant recurrence during the surveillance period were treated with systemic therapy.

Patients included in the analysis had a median age of 72 years and 79% were male. Additionally, 55% of patients had formerly smoked, with 20% of patients identifying as current smoking. Patients primarily had an ECOG performance status of 0 (66%) or 1 (32%). The median creatinine clearance was 59 mL/min, the median tumor size was 4.1 cm and 25% of patients had hydronephrosis.

Patients had clinical stage 2 (59%), 3 (34%), or 4 (7%) disease, and the most common histologies were pure urothelial carcinoma (UC; 63%), squamous UC (23%) and plasmacytoid variant UC (13%). A total of 30% and 18% of patients had carcinoma-in-situ and lymphovascular invasion, respectively. Overall, 41% of patients experienced disease recurrence, with 20% of patients experiencing local recurrence, 14% experiencing recurrence requiring cystectomy and 21% experiencing distant recurrence.

The primary NAC regimens were gemcitabine/cisplatin every 21 days (34%) or split gemcitabine/cisplatin every 21 days (57%). Overall, 5%, 32% and 63% of patients underwent two, three and four NAC cycles, with 95% of patients completing planned NAC treatment. The most common grade 3 (severe) or 4 (life-threatening) NAC-related toxicities included neutropenia (11%), thrombocytopenia (4%), infection (4%) and anemia (2%). NAC dose reductions occurred in 55% of patients with a median dose reduction percentage of 25%, and 39% of patients experienced NAC dose delays.

Additionally, the reasons for administering trimodality therapy included patient preference (59%), comorbidities related to radical cystectomy (36%) or some combination of both factors (4%). Most patients had a planned radiation therapy dose of 60 Gy or greater (91%), and all patients completed planned radiation. Furthermore, 86% of patients completed 60% or more of planned concurrent cisplatin dosing.

“Long-term outcomes of neoadjuvant chemotherapy (NAC) before bladder-sparing chemoradiotherapy (CRT) for patients with nonmetastatic, muscle-invasive bladder cancer (MIBC),” by Dr. Meghan E. Mahoney, et al., 

Neoadjuvant cisplatin-based chemotherapy combined with bladder-sparing concurrent chemoradiation therapy demonstrates long-term efficacy and safety in nonmetastatic muscle-invasive bladder cancer (MIBC). After a median follow-up of 96 months, the median disease-free survival (DFS) was 56.6 months, with a five-year DFS rate of 49.2%. The median bladder intact DFS was 45.6 months, and the five-year rate was 47.6%. Overall survival (OS) reached a median of 105 months, with a five-year OS rate of 62.2%. Trimodality therapy was chosen due to patient preference and comorbidities.

For some patients with bladder cancer, neoadjuvant chemotherapy plus bladder-saving concurrent chemoradiation therapy was effective in the long term.

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

Palliative care in young adults with early-onset colorectal cancer reduced invasive procedures, costs and increased DNR orders, improving end-of-life comfort.

Among patients with early-onset colorectal cancer (CRC), palliative care involvement may reduce invasive and uncomfortable intervention use, resulting in a subjective improvement in patient end-of-life (EOL) comfort, according to findings from a real-world study presented at the 

2025 ASCO Gastrointestinal Cancer Symposium

Data revealed that among patients with early-onset CRC who died during hospitalization, palliative care was associated with significant reductions in multiple invasive interventions. Between two cohorts, one treated with palliative care (2,425 patients), and another not treated with palliative care (1,635 patients), blood transfusion was reported in 14.8% and 22.6% of patients, mechanical ventilation was reported in 20.4% and 43.4% of patients and vasopressor use was reported in 6.2% and 8.6%, respectively.

Additional data revealed a significant reduction in total charges with palliative care, with a median of $99,367 (SD, 151,864) versus $131,993 (SD, 206,404) without palliative care. Furthermore, do not resuscitate (DNR) orders were significantly increased with palliative care, which was reported in 83.3% of this cohort versus 44.6% in patients without palliative care.

Vasopressor: medicine that raises blood pressure.

Overall survival: the time a patient lives, regardless of disease status.

“Inclusion of palliative care in terminal hospital stays for patients with early-onset CRC was associated with less use of invasive and uncomfortable interventions, resulting in significantly reduced expenditure on futile measures, and likely a subjective improvement in patient [EOL] comfort,” Dr. Suriya Baskar, resident physician in the Internal Medicine Department at the Brooklyn Hospital Center, wrote in the study with coinvestigators. “The results of this study support the integration of palliative care in [patients with] early-onset [CRC] presenting with advanced disease.”

According to the National Cancer Institute’s website, palliative care aims to improve quality of life and reduce pain for individuals with serious or life-threatening illnesses, such as cancer. The goal is to prevent or treat disease symptoms and treatment side effects as early as possible. This care also addresses the psychological, social and spiritual issues arising from the illness or its treatment. For patients with cancer, palliative care can include therapies like surgery, radiation or chemotherapy to remove, shrink or slow tumor growth causing pain. It may also involve support for family and caregivers. Palliative care can be provided alongside other treatments from diagnosis to end of life.

The median age of patients receiving palliative care was 42.1 years compared to 41.9 years for those not receiving such care. Women made up 44.3% of the palliative care group and 39.8% of the group that did not receive palliative care.

The mean length of hospital stay was 8.8 days for patients receiving palliative care and 9.1 days for those who did not. Chemotherapy was administered to 2.9% of the palliative care group and 2.8% of the other group.

The study was conducted in the context of prior proven benefits associated with palliative care in elderly patients with advanced cancers, with an identified paucity of data regarding the benefits of palliative care among younger patients with aggressive disease. A study published in 

 found that among patients with advanced cancers, those who received early palliative care (73 patients) experienced better quality of life (QOL) at 18 months than those who did not (71 patients).

Furthermore, a greater difference in existential well-being index was observed among patients who received palliative care versus those who did not at 24-week follow-up (0.82 points). Additionally, two-year overall survival was significantly improved among patients who received early palliative care 10 or more times.

"Impact of inpatient palliative care on end-of-life care among patients with early-onset colorectal cancer" by Dr. Suriya Baskar, et al., 

Palliative care involvement in early-onset colorectal cancer (CRC) patients significantly reduces invasive interventions and hospital charges, enhancing end-of-life comfort. A study presented at the 2025 ASCO Gastrointestinal Cancer Symposium showed that palliative care led to fewer blood transfusions, mechanical ventilation, and vasopressor use. It also increased do-not-resuscitate orders and reduced hospital costs. The study supports integrating palliative care for advanced early-onset CRC patients, aligning with previous findings of improved quality of life and survival in advanced cancer patients receiving early palliative care.

Palliative care for young adults with colorectal cancer reduced invasive procedures, costs and increased DNR orders.

Russ Conroy

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

Initial Enhertu Combo Improves Survival in HER2+ Advanced Breast Cancer

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

Palliative Care May Reduce Invasive Intervention Use in Early-Onset CRC

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