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Zongertinib provided clinical benefit in previously treated advanced non–small cell lung cancer harboring HER2 mutations.

Zongertinib Yields Clinical Benefit in Previously Treated, HER2-Mutated, Advanced NSCLC

Talazoparib plus enzalutamide improved rPFS vs placebo plus enzalutamide in patients with mCRPC with or without AR alterations. 

Talazoparib Plus Enzalutamide Improves rPFS Regardless of AR Alteration Status in mCRPC

Olaparib plus pembrolizumab was safe and effective in HRR gene–mutated and/or HRD-positive advanced tumors.

Olaparib Plus Pembrolizumab Shows Efficacy in HRR Gene–Mutated Advanced Tumors With/Without HRD Positivity

Penpulimab plus chemotherapy improved progression-free survival in recurrent or metastatic nasopharyngeal carcinoma.

First-Line Penpulimab Plus Chemo Extends PFS in Recurrent or Metastatic Nasopharyngeal Carcinoma

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 in November 2021 as a senior editor and became the website's managing editor in October 2023. Before arriving at MJH Life Sciences, he spent nearly a decade covering professional and high school sports—including the New Jersey Devils and the NHL from 2016 to 2021—for The Star-Ledger and NJ.com. Email: chryan@onclive.com

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. A recent College of New Jersey graduate, Jax majored in Journalism/ Professional Writing with minors in Public Health and Anthropology. He is also pursuing a Master's Degree in Public Health, concentrating on health communications.

China’s NMPA approved ivonescimab for the first-line treatment of PD-L1–positive advanced non–small cell lung cancer.

Ivonescimab Wins NMPA Approval in China for First-Line, PD-L1+ Advanced NSCLC

Linvoseltamab earned EC approval for relapsed/refractory multiple myeloma after at least 3 prior lines of therapy.

Linvoseltamab Receives EC Approval for Heavily Pretreated R/R Myeloma

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Jason A. Mouabbi, MD, discusses the use of ctDNA to enhance early detection of ESR1 or other resistance mutations in HR-positive breast cancer. 

Proactive ctDNA Monitoring May Guide Earlier Intervention in Endocrine-Resistant HR+/HER2– Breast Cancer

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All-oral doublet regimens (eg, acalabrutinib plus venetoclax) are extremely exciting to the field of chronic lymphocytic leukemia (CLL), as many patients prefer oral-only therapies. However, identifying ideal patients to receive doublet versus triplet versus continuous Bruton tyrosine kinase inhibitor (BTKi) monotherapy in the first-line setting is still evolving.

Treatment sequencing in CLL will become increasingly more difficult with new combination regimens becoming more widely used in the first-line setting.

The optimal sequencing of BTK inhibitors and chimeric antigen receptor T-cell therapy (CAR-T) is still being debated.

Bispecific antibodies and BTK degraders remain exciting emerging therapies in the relapsed and/or refractory CLL population.

The faculty expressed enthusiasm for all-oral doublet regimens such as AV (acalabrutinib plus venetoclax), which have already been included in NCCN guidelines. However, distinguishing which patients would benefit most from AV versus currently available therapies like VEN+O (venetoclax plus obinutuzumab) remains difficult in the absence of data from direct comparative trials.

Clinicians continue to debate about first-line triplet therapies, as they are concerned about high infection rates and cytopenias. They were excited about the data with pirtobrutinib plus VEN+O from the American Society of Hematology (ASH) 2024 conference. Another emerging combination includes AVO (AV plus obinutuzumab) in high-risk patients from a phase two study lead by

 as the AMPLIFY trial excluded patients with 

aberration. The faculty agreed that selecting the appropriate patient for these novel combination regimens is an ongoing discussion.

Treatment Sequencing in CLL: Second-Line Treatment Options

Faculty members largely agreed that acalabrutinib and zanubrutinib are comparable in the second-line setting for those who received fixed-duration therapy in the first-line setting. The faculty largely agreed that the ideal time window of retreatment with venetoclax is still debatable, but 1 year of progression- free survival with VEN+O would be too short for such consideration. With new combination therapies (eg, AV and/or AVO) most likely getting approved soon, sequencing of therapies will be complicated, and analyzing durability of responses will be increasingly important.


Overall, the faculty agree that pirtobrutinib is a well-tolerated agent. However, the ideal role of pirtobrutinib in R/R CLL as a second-line versus third-line treatment remains debated. There is debate on the utility of the control arm of the phase three trial that was presented at ASH 2024 (BRUIN CLL-321), with some experts no longer viewing BR (bendamustine plus rituximab) or IdelaR (idelalisib plus rituximab) as a standard of care.

Managing R/R CLL After BTKi- and Venetoclax-Containing Regimens

The discussion on R/R CLL highlighted the lack of consensus regarding optimal sequencing after receiving both covalent BTKi and venetoclax-containing regimens. Faculty members expressed mixed opinions on the efficacy of CAR-T in CLL. Some cited promising long-term remission rates; others noted the difficulty in selecting appropriate candidates, as the majority of the CLL population are elderly and may not tolerate CAR-T.

Emerging treatments such as bispecific antibodies (eg, epcoritamab) and BTK degraders were highlighted as potential game-changers in CLL management. Faculty members noted that bispecific antibodies may be an alternative to CAR-T particularly given the logistical challenges of CAR-T manufacturing and administration. The faculty acknowledged that the durability of responses of these novel therapies must be understood, as those data are being gathered.

The increasing treatment options available make this an exciting time for CLL treatment; however, it also is a more challenging time, since it is unclear who are the most ideal candidates for doublet or triplet therapies in the frontline setting. The faculty agree that there are multiple treatment approaches in the high-risk population. These include minimal residual disease testing to decide to discontinue or de-escalate therapy; however, this is primarily done in the clinical trial setting.

The faculty agree that the ideal role of BTK inhibitors and CAR-T must be understood further, and strategies to improve durability of responses in the relapsed and/or refractory population must be the focus.

Head-to-head clinical trials comparing novel combination regimens, such as AV versus Ven+O, are necessary to guide treatment selection. Furthermore, optimizing sequencing strategies after use of doublet or triplet regimens remains a gray area, as the durability of responses is unknown for this patient population. Long-term follow-up studies and real-world data for novel or investigational therapies are critical to understanding their optimal use.

The discussion underscores the rapidly evolving CLL landscape and the importance of continued research to refine sequencing strategies and to individualize treatment selection. The faculty largely agree on treatment strategies for a “typical” CLL patient, although differing opinions on pirtobrutinib’s role and CAR-T sequencing highlight ongoing debates in the field. As novel therapies continue to emerge, their integration into a treatment paradigm that optimizes patient outcomes while minimizing toxicity will remain a challenge.

Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

, Version 2.2025. Accessed February 19, 2025. 

https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf

Brown JR, Seymour JF, Jurczak W, et al. Fixed-duration acalabrutinib plus venetoclax with or without obinutuzumab versus chemoimmunotherapy for first-line treatment of chronic lymphocytic leukemia: interim analysis of the multicenter, open-label, randomized, phase 3 AMPLIFY trial. 

. 2024;144(suppl 1):1009. doi:10.1182/blood-2024-200701

Jain N, Ferrajoli A, Swaminathan M, et al. Combined pirtobrutinib, venetoclax, and obinutuzumab as first-line treatment of chronic lymphocytic leukemia. 

. 2024;144(suppl 1):1011. doi:10.1182/blood-2024-211454

Davids MS, Ryan CE, Lampson BL, et al. Phase II study of acalabrutinib, venetoclax, and obinutuzumab in a treatment-naïve chronic lymphocytic leukemia population enriched for high-risk disease. 

. Published online December 7, 2024. doi:10.1200/JCO-24-02503

Sharman JP, Munir T, Grosicki S, et al. BRUIN CLL-321: randomized phase III trial of pirtobrutinib versus idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma. 

. 2024;144(suppl 1):886. doi:10.1182/blood-2024-198147

Siddiqi T, Gauthier J, Kenderian SS, et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL): updated follow-up of Transcend CLL 004. 

. 2024;144(suppl 1):4633. doi:10.1182/blood-2024-200840

Wierda WG, Dorritie K, Gauthier J, et al. Lisocabtagene maraleucel (liso-cel) combined with ibrutinib (ibr) for patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): primary results from the open-label, phase 1/2 Transcend CLL 004 study. 

. 2024;144(suppl 1):887. doi:10.1182/blood-2024-200339

Frost BF, Frey N, Hexner EO, et al. Curing CLL: long-term outcomes of chronic lymphocytic leukemia patients with at least one year of response to CART-19 therapy. Blood. 2024;144(suppl 1):588. doi:10.1182/blood-2024-204197

Danilov A, Fakhri B, Awan FT, et al. Epcoritamab monotherapy in patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL): results from CLL expansion and optimization cohorts of Epcore CLL-1. 

. 2024;144(suppl 1):883. doi:10.1182/blood-2024-199708

Shah NN, Omer Z, Collins GP, et al. Efficacy and safety of the Bruton's tyrosine kinase (BTK) degrader NX-5948 in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): updated results from an ongoing phase 1a/b study. 

. 2024;144(suppl 1):884. doi:10.1182/blood-2023-194839

Thompson MC, Parrondo RD, Frustaci AM, et al. Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: results from the phase 1 CaDAnCe-101 study. 

. 2024;144(suppl 1):885. doi:10.1182/blood-2024-199116

The landscape of chronic lymphocytic leukemia (CLL) treatment is rapidly evolving with the introduction of all-oral doublet regimens, such as acalabrutinib plus venetoclax, and emerging therapies like bispecific antibodies and BTK degraders. The optimal sequencing of these therapies, including BTK inhibitors and CAR-T, remains a topic of debate. Clinicians face challenges in selecting appropriate patients for novel combination regimens and determining the ideal sequencing strategy. Continued research and head-to-head clinical trials are essential to refine treatment strategies and improve patient outcomes.

On February 13, 2025, a select group of experts in chronic lymphocytic leukemia (CLL) participated in a virtual workshop to discuss the evolving treatment landscape of CLL and discussed subjects ranging from treatment of newly diagnosed patients to therapies for those relapsed/refractory (R/R) disease. Moderated by Alexey V. Danilov, MD, PhD, the discussion covered insights into emerging treatment approaches, novel therapeutic strategies, and sequencing of available therapies to optimize patient outcomes.

This article was supported in part by Eli Lilly. Content independently developed and published by OncLive.

Scientific Interchange & Workshop

Clinical

Bridging Data and Expert Insights: Paving the Way for Improved CLL Outcomes

Núria Agustí Garcia, MD, discusses patient eligibility in a cohort study assessing adjuvant chemoradiotherapy vs radiotherapy alone in patients with cervical cancer.

Dr Agustí Garcia on Patient Eligibility for Evaluating Chemoradiotherapy vs Radiotherapy Alone in Intermediate-Risk Cervical Cancer

“[In this study,] we included patients who have undergone radical hysterectomy with negative lymph nodes, and we divided the population based on whether they received radiotherapy alone vs chemoradiation.”

Núria Agustí, MD, a postdoctoral fellow at MD Anderson Cancer Center, discussed the patient population included in a cohort study evaluating adjuvant chemoradiotherapy vs radiotherapy alone in the treatment of intermediate-risk cervical cancer.

The study used data retrieved from the National Cancer Database between 2010 and 2020, Agustí Garcia began. She emphasized that data prior to 2010 were not included because there were no values for lymphovascular space invasion (LVSI), and there also wasn’t information on surgical approaches. These variables could directly affect primary outcomes, which is largely why prior data were excluded, she explained.

The patient population included those with cervical cancer who underwent radical hysterectomy with negative lymph nodes and were stratified based on whether they had received adjuvant chemoradiotherapy or radiotherapy alone, Agustí noted. Patients not included on the study had high-risk disease factors, such as positive margins, parametrial extension, and positive lymph nodes. Furthermore, the Sedlis criteria for the study included the intermediate-risk group of patients with cervical cancer, Agustí said. For missing values, multiple imputation allowed for a more accurate representation of the patient population, she added. After imputation, the propensity score was matched 1:1 to control the cofounders related to clinical, pathologic, and demographic variables to have a well balanced population, she said.

Of note, a total of 1116 patients were identified ,and 43.5% had received concurrent chemoradiotherapy, according to the findings from the study published in 

. Patients with adenocarcinoma or adenosquamous histology more commonly received chemotherapy compared with those with squamous cell carcinoma (risk ratio [RR]; 12.6; 95% CI, 1.10-1.44) and those with tumors larger than 4 cm vs tumors less than 4 cm (RR, 1.31; 95% CI, 1.14-1.51).

In the study, a subgroup analysis was also performed based on 5 variables that could affect the primary outcome of survival, based on prior evidence, Agustí noted. She concluded that these variables included the LVSI, tumor size, histology, surgical approach, and radiotherapy use.

The study also evaluated the potential association of unmeasured confounders using the E-value, a sensitivity analysis that quantified the strength of association an unmeasured confounder must have with the exposure and outcome to explain an observed association. A sensitivity analysis was also performed using a complete case approach and compared the results with those from the fully imputed datasets. 

The results of this cohort study suggested that adding chemotherapy to radiotherapy was not associated with improved overall survival (OS) in patients with intermediate-risk cervical cancer. The subgroup analysis did not show any differences in OS according to the use of chemoradiotherapy or radiotherapy alone.

Núria Agustí, MD, discusses patient eligibility in a cohort study assessing adjuvant chemoradiotherapy vs radiotherapy alone in patients with cervical cancer.

Dr Agustí on Patient Eligibility for Evaluating Chemoradiotherapy vs Radiotherapy Alone in Intermediate-Risk Cervical Cancer

Findings from CALGB (Alliance)/SWOG 80702

Dr. Benjamin Weinberg presents findings from a ctDNA-based analysis of the CALGB/SWOG 80702 trial, showing that circulating tumor DNA status may help identify patients with stage III colon cancer who could benefit from celecoxib added to standard adjuvant chemotherapy, offering a potential biomarker-driven approach to personalized treatment.

Prognostic and Predictive Role of Circulating Tumor DNA (ctDNA) in Stage III Colon Cancer Treated With Celecoxib: Findings from CALGB (Alliance)/SWOG 80702

Genotype-Directed Therapies for HR+/HER2– Advanced Breast Cancer

DISCLAIMER: In the Phase 3 INAVO-120 Study evaluating inavolisib+palbociclib+fulvestrant, the correct PFS data is 15 months vs. 7.3 months, not 24 vs. 15 months as stated; 2) Time to chemotherapy data was not available at primary analysis; 3) The safety profile characterization was incomplete - the treatment showed a low discontinuation rate of only 6% due to adverse events, with grade 3+4 AEs (specific to Rash & Nausea) were 0%.

Video content above is prompted by the following:

What are the more genotype-directed options for advanced HR+/HER2–- disease (PI3K/AKT/mTOR inhibitors, ADCs, etc.) ?

How, and for what patient populations, are these being used based on the most recent data? What are your impressions of each of these regimens?

– How might the recent first-line inavolisib approval change the treatment paradigm? (approved in combination with palbociclib and fulvestrant for patients with

-mutated, HR+, HER2–- la /metastatic breast cancer mBC that who progress on or relapse within 12 months after completing adjuvant endocrine therapy)change the treatment paradigm? 

Panelists discuss genotype-directed treatment options for advanced HR+/HER2– disease, including PI3K/AKT/mTOR inhibitors and antibody-drug conjugates (ADCs), their use based on recent data, impressions of these regimens, and how the recent first-line approval of inavolisib in combination with palbociclib and fulvestrant for PI3K-mutated HR+/HER2– metastatic breast cancer may change the treatment paradigm.

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OncLive Peer Exchange® 

Real-world comparison of the efficacy and safety of atezolizumab versus durvalumab in extensive-stage small cell lung cancer

CORRECTION: Atezolizumab has an Overall Survival (OS) of 

This research represents a retrospective analysis utilizing real-world observational data. As such, the findings and conclusions presented herein are inherently exploratory.

Dr. Bruna Pellini presents key data comparing real-world outcomes of atezolizumab versus durvalumab in extensive-stage small cell lung cancer (ES-SCLC), demonstrating a significant overall survival advantage and lower immune-related adverse events with durvalumab, while progression-free survival remained comparable between the two treatments.

RLY-2608

Sarah Sammons, MD, highlights ReDiscover trial findings, showcasing the durable efficacy, potent mutant-selective targeting, and favorable safety profile of RLY-2608 combined with fulvestrant in patients with PIK3CA-mutant HR+/HER2− advanced breast cancer, validating its potential as the first allosteric, pan-mutant PI3Kα inhibitor.

Lyudmila A. Bazhenova, MD, UC San Diego Health

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