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Adding sonrotoclax to zanubrutinib led to deep and durable response in relapsed or refractory mantle cell lymphoma, according to EHA Congress data.

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Michelle Kirschner, RN, MSN, ACNP, APRN-BC, is a nurse practitioner and director of program development at the Cancer Survivorship and Supportive Care Professionals Network.

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Ronald Bleday, MD, is the section chief of the Division of Colorectal Surgery and vice chair for quality and patient safety in the Department of Surgery at Brigham and Women’s Hospital in Boston, Massachusetts.

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Paolo Tarantino, MD, PhD, is a clinical research fellow at Dana-Farber Cancer Institute.

Each component of an antibody-drug conjugates—payload, linker, and antibody—play a unique role in building the treatment’s use and safety profile.

ADCs Are “Legos,” Customize Cancer Treatment By Target, Safety

Olaparib (Lynparza) provided the greatest overall survival (OS) benefit for patients with platinum-sensitive relapsed ovarian cancer harboring germline or somatic 

 mutations, as compared to other cohorts, in which efficacy was also observed in a final OS analysis of the phase 2 LIGHT study (NCT02983799).

 showed that at a median follow-up in of 26.3 months (range 0.6-36.9 months) for the efficacy analysis set (n = 270) and a final data cutoff of August 27, 2020, the 18-month OS rates for the germline 

 mutation cohort (cohort 1; n = 75), somatic 

 mutation cohort (cohort 2; n = 25), the homologous recombination deficiency (HRD)–positive, non-

 mutation cohort (cohort 3; n = 68), and HRD-negative cohort (cohort 4; n = 89) were 86.4% (95% CI, 76.2%-92.4%), 88.0% (95% CI, 67.3%-96.0%), 78.6% (95% CI, 66.6%-86.8%), and 59.6% (95% CI, 48.6%-68.9%), respectively. The OS rates at 1 year in the respective cohorts were 94.6% (95% CI, 86.3%-97.9%), 92.0% (95% CI, 71.6%-97.9%), 89.4% (95% CI, 79.1%-94.8%), and 71.9% (95% CI, 61.3%-80.1%).

“The final OS analysis of the LIGHT study of olaparib treatment in platinum-sensitive relapsed ovarian cancer showed that the highest OS rates were observed in the germline/somatic 

-mutated cohorts,” lead study author Ying L. Liu, MD, MPH, a gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, and coauthors wrote in the paper. “Among patients without a 

 mutation, OS rates were highest in the HRD-positive cohort.”

The open-label, nonrandomized, noncomparative, multicenter LIGHT study prospectively assessed olaparib in the treatment of patients with platinum-sensitive relapsed ovarian cancer who received 1 or more prior lines of platinum-based chemotherapy with a known 

Findings from the primary analysis of the study showed the overall response rates (ORRs) were 69.3% (95% CI, 57.6%-79.5%), 64.0% (95% CI, 42.5%-82.0%), 29.4% (95% CI, 19.0%-41.7%), and 10.1% (95% CI, 4.7%-18.3%) in cohorts 1, 2, 3, and 4, respectively.

The study included 272 patients, of which 270 met the inclusion criteria for the efficacy analysis; 271 patients were included in the safety analysis.

 Eligibility criteria included patients at least 18 years of age with histologically confirmed, relapsed high-grade serious or endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer per RECIST criteria 1.1; at least 1 assessable lesion at baseline; disease progression at least 6 months after the end of the last platinum-based chemotherapy regimen; and no previous treatment with PARP inhibitors.

Patients were assigned to cohorts 1, 2, 3, and 4 based on their 

 mutation and HRD statuses. An unassigned cohort included patients who were not assigned to a specific cohort because of missing or failed 

The primary end point was investigator-assessed ORR per RECIST 1.1.

 Secondary end points were OS and safety.

In cohorts 1 (n = 75), 2 (n = 26), 3 (n = 68), and 4 (n = 90), median ages at baseline were 61 years (range, 42-80), 71 years (range, 50-90), 64 years (range, 38-88), and 69 years (range, 35-91).

 Tumor grade in the respective cohorts were mostly high grade (68.0%; 80.8%; 77.9%; 74.4%) and most had an ECOG performance status of 0 (77.3%; 50.0%; 70.6%; 62.2%).

At data cutoff for the final OS analysis, the discontinuation rates for olaparib in cohorts 1, 2, 3, and 4 were 78.7%, 92.0%, 89.7%, and 98.9%, respectively.

 In the unassigned cohort (n = 13), all patients received treatment; 92.3% discontinued treatment, and 7.7% continued treatment at data cutoff.

“A similar pattern of relative benefit between cohorts was observed when patients were stratified by number of prior chemotherapy regimens [1 and 2 or more],” study authors stated. “No new safety signals were observed at the final LIGHT OS analysis compared with the primary analysis and prior olaparib studies.”

Data from the final analysis showed the median total duration of treatment for the overall population was 7.4 months (range, 0.5-30.6). Of note, 29.5% of patients required dose interruptions and 26.9% needed dose reductions; adverse effects (AEs) led to dose interruptions and dose reductions in 26.2% and 21.8% of patients, respectively. Treatment-emergent AEs (TEAEs) leading to treatment discontinuation occurred in 5.2% of patients. The most common TEAEs leading to discontinuation included fatigue/asthenia and nausea, which were each reported in 2 patients (0.7%).

The most common serious treatment-related AEs of any grade included anemia (1.1%) pneumonia (0.7%), and abdominal pain (0.7%). AEs of special interest included 1 patient (0.4%) with grade 2 pneumonitis 57 days after beginning olaparib, and 1 other patient with grade 2 pulmonary fibrosis 110 days after beginning olaparib. Grade 4 acute myeloid leukemia 711 days after beginning olaparib treatment occurred in 1 patient (0.4%); however, this was considered unrelated to olaparib.

AEs led to death in 2 patients (0.7%) but were deemed unrelated to olaparib, including a death from atrial fibrillation in the somatic 

 mutation cohort 46 days after beginning olaparib treatment, along with a death from intestinal perforation that occurred during the survival follow-up period of the analysis from the unassigned cohort.

Liu YL, Mathews CA, Simpkins F, et al. Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis. 

. 2025;131(2):e35707. doi:10.1002/cncr.35707

Cadoo K, Simpkins F, Mathews C, et al. Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis. 

. 2022;166(3):425-431. doi:10.1016/j.ygyno.2022.06.017

Patients with relapsed ovarian cancer who had germline or somatic BRCA mutations saw greater OS with olaparib, according to data from the LIGHT trial.

Olaparib Increases OS in Patients with Germline/Somatic BRCA+ Relapsed Ovarian Cancer

The FDA has granted accelerated approval to the antibody-drug conjugate (ADC) datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) for the treatment of adults with 

-mutant non-small cell lung cancer (NSCLC) following previous EGFR-targeted therapy and platinum-based chemotherapy.

The approval is based on findings from the multicenter single-arm phase 2 TROPION-Lung05 trial (NCT04484142) and the multicenter, open-label, randomized controlled phase 3 TROPION-Lung01 trial (NCT04656652).

According to the FDA’s announcement, primary end points of objective response rate (ORR) and median duration of response (DOR), as assessed by blinded independent central review via RECIST v1.1, were found to be 45% (95% CI, 35%-54%) and 6.5 months (95% CI, 4.2-8.4), respectively.

The label for the TROP2-directed ADC, previously referred to as DS-1062a, includes warnings for interstitial lung disease (ILD) and pneumonitis, ocular adverse effects (AEs), stomatitis and oral mucositis, and embryo-fetal toxicity.

Additionally, it cites stomatitis, nausea, fatigue, leukocytopenia, hypocalcemia, alopecia, lymphocytopenia, decreased hemoglobin, constipation, neutropenia, dry eye, emesis, increased alanine aminotransferase, keratitis, increased aspartate aminotransferase, and increased alkaline phosphatase, as the most common AEs, including abnormal laboratory reports, associated with Dato-DXd.

Previous findings from the TROPION-Lung01 trial, which evaluated the efficacy and safety of Dato-DXd in patients with pretreated advanced or metastatic NSCLC, were reported in the 

 Patients enrolled in TROPION-Lung01 were randomly assigned 1:1 to treatment with 6 mg/kg of Dato-DXd (n = 299) or 75 mg/m

 of docetaxel (n = 305) administered intravenously once every 3 weeks until progression, unacceptable toxicity, or other reasons if applicable.

The primary analysis revealed a median progression-free survival (PFS) of 4.4 months (95% CI, 4.2-5.6) and 3.7 months (95% CI, 2.9-4.2) in the Dato-DXd and docetaxel arms, respectively. Likewise, the median DOR for all patients enrolled in the Dato-DXd arm was 7.1 months (range, 5.6-10.9), compared with 5.6 months (range, 5.4-8.1) in the docetaxel arm.

The median ages of patients in the Dato-DXd and docetaxel arms were 63 years (range, 26.0-84.0) and 64 years (range, 24.0-88.0), respectively. Stratification factors included histology, actionable genomic alteration status, geographic region, and immediate previous therapy with an anti-PD-1/PD-L1.

Treatment-related AEs of grade 3 or higher were reported in 25.6% of patients in the Dato-DXd arm and 42.1% of patients in the docetaxel arm. Any-grade adjudicated drug-related ILD or pneumonitis occurred in 8.8% and 4.1% of patients, respectively.

Dato-DXd’s efficacy and safety in treating advanced or metastatic NSCLC on or after targeted therapy and platinum-based chemotherapy was also evaluated in TROPION-Lung05.

 Out of 137 patients receiving 1 or more doses of Dato-DXd, 71.5% of patients received 3 or more lines of prior therapy, and 56.9% had 

Median DOR was 7.0 months (95% CI, 4.2-9.8), with an overall disease control rate of 78.8% (95% CI, 71.0%-85.3%). Of patients with 

 mutations, the ORR was 44%, compared with 35.8% in the overall population enrolled.

Grade 3 or higher TEAEs were reported in 28.5% of patients. The most common TRAE was stomatitis, occurring at any grade in 56.2% of patients and at grade 3 or higher in 9.5% of patients. Additionally, 5 patients (3.6%) had adjudicated treatment-related ILD or pneumonitis, with 1 (0.7%) having a grade 5 event. Altogether, no new safety signals were found.

FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. FDA. News release. June 23, 2025. Accessed June 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-datopotamab-deruxtecan-dlnk-egfr-mutated-non-small-cell-lung-cancer

Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. 

. 2025;43(3):260-272. doi:10.1200/JCO-24-01544

Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. 

. 2025;43(10):1254-1265. doi:10.1200/JCO-24-01349

Dato-DXd was granted accelerated approval for use in adults with EGFR-mutated NSCLC after EGFR-targeted therapy and platinum-based chemotherapy.

Dato-DXd Greenlit by FDA for Previously Treated EGFR-Mutated NSCLC

Keeping a positive outlook is proven to help with stress management, but when someone says to "think positive" or "be optimistic" during a time such as a cancer diagnosis, it can be much easier said than done. We know that cancer isn't all rainbows and butterflies, and once a patient enters a dark mindset, it can be hard to get out of it. But most of us have that one message of hope and inspiration that somehow manages to help bring some perspective and optimism to a situation.

You beat cancer by how you live, why you live, and in the manner in which you live

. — Stuart Scott. Live your life by your own terms, not cancer's.

Remember how far you've come, not just how far you have to go. You may not be where you want to be, but neither are you where you used to be

. It can be easy to get caught up in how far you have to go. Don't forget to look back, and recognize how far you have come. Every day brings you one step closer.

You are braver than you believe, stronger than you seem, smarter than you think, and twice as beautiful as you'd ever imagined

. Don't let cancer cause you to sell yourself short or forget your worth.

When you have exhausted all possibilities, remember this: You haven't

. —Thomas Edison. Keep searching for what you're looking for. You will find it.

Your life is your story. Write well. Edit Often

. You can't control what happens to you, but you can control the way that you handle it. What do you want your story to say?

. You are here, breathing and living life. Even if it's not the life you want or hoped for, it's life. There's always something to be thankful for.

. Every small step counts. You might not reach your goal today but that is okay.

Never be ashamed of a scar. It simply means you were stronger than whatever tried to hurt you

. Everyone has scars—whether you can see them or not. Wear yours with pride.

When it rains, look for rainbows. When it's dark, look for stars

. It may be hard to find your silver lining during a cancer diagnosis, but it's there. If you look for it, you will find it.

Optimism: someone who figures that taking a step backward after taking a step forward is not a disaster; it's more like a cha-cha. 

You may not be where you want to be right now, but you're just doing the dance that is called life.

I have loved the stars too fondly to be fearful of the night

. — Galileo. If you loved your life before cancer, do not be afraid of life after cancer. You will find beauty again.

Surround yourself with only people who are going to lift you higher

. — Oprah Winfrey. There is no time for negative energy during cancer .You need to be around people who inspire, challenge, and make you better.

. The bad thoughts will try and sneak in, but don't let them. Focus only on the good thoughts.

Don't look back. You're not going that way

. Don't waste time worrying about the things that you cannot control; such as the past. Keep moving forward.

. There's no other option. Tell yourself this affirmation every day - through treatments, doctors visits, and whatever else comes your way.

. You are not defined by what you are going through. Cancer will never have you. You are much more than your disease.

. Cancer is NOT a death sentence. It's just one word in your sentence; one part of your life.

. Nobody's perfect. If you feel broken, don't let that determine your worth. You can still do so much.

For patients dealing with cancer, a daily dose of inspiration may make a big difference in their outlook on life. 

Paolo Tarantino, MD, PhD

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