The 2023 American Society of Clinical Oncology (ASCO) Annual Meeting will feature significant results from numerous clinical studies in both solid tumors and hematologic malignancies. As part of CCO’sF Independent Conference Coverage of ASCO 2023, oncology experts have identified their most anticipated abstracts, listed below. Remember to check the CCO website often as the meeting unfolds for downloadable slidesets summarizing the data from these studies and more. After the meeting, join us for our live, interactive “Conference to Clinic” webinar as experts discuss some of the most impactful abstracts presented during ASCO 2023 and answer audience questions on the data. Finally, read our CME-certified online modules providing expert analyses and insights into the clinical implications of the new findings.

Top Picks: Breast Cancer
Sara Tolaney, MD, MPH, and Erika Hamilton, MD, identified the following as their top abstracts to watch.

• NATALEE: phase III study evaluating addition of adjuvant ribociclib for 3 years to standard endocrine therapy (ET) for patients with intermediate- and high-risk hormone receptor (HR)‒positive early breast cancer (EBC) (abstract LBA500). Positive data could support approval of a second CDK4/6 inhibitor in the adjuvant setting with a broader eligibility beyond the high-risk patients eligible for adjuvant abemaciclib per monarchE.
• PHERGain: randomized phase II trial looking at PET response–guided neoadjuvant therapy for HER2-positive EBC (abstract LBA506); important data comparing 3-year invasive disease–free survival for a chemotherapy (CT)-free approach with HP vs standard TCHP.
• SONIA: investigator-initiated phase III study comparing CDK4/6 inhibition in the first-line vs second-line setting for HR-positive/HER2-negative advanced breast cancer (abstract LBA1000); results from this study will help determine whether there is an optimal position for CDK4/6 inhibition in advanced disease. This will be particularly informative in making sequencing decisions for patients who are older and/or have more comorbidities.
• PALMIRA: phase II study comparing second-line treatment with an alternative ET with or without palbociclib maintenance in patients who progressed after having clinical benefit with first-line or adjuvant palbociclib plus ET (abstract 1001). Data from this study will help determine whether second-line ET backbones should be combined with continued CDK4/6 inhibitors or targeted agents (eg, mTOR, PI3K, or AKT inhibitors).

Additional studies to watch in breast cancer include:

• TROPiCS-02: final overall survival analysis of sacituzumab govitecan vs treatment of physician’s choice in second- and later-line HR-positive/HER2-negative metastatic breast cancer (MBC) (abstract 1003).
• Phase II study results for antitumor activity and safety of HER3-DXd, a HER3-targeted antibody–drug conjugate (ADC), in patients with HER2-negative MBC (abstract 1004).
• Age-specific analysis of trastuzumab deruxtecan safety and efficacy in patients with HER2-positive MBC enrolled on DESTINY-Breast01, -02, and -03 (abstract 1006).
• ctDNA analysis of ESR1 mutation kinetics among patients with estrogen receptor‒positive/HER2-negative MBC randomized to continue receiving aromatase inhibitor plus palbociclib or switched to fulvestrant plus palbociclib in the PADA-1 trial (abstract 1002).
• monarchE: subgroup analysis by age of efficacy and safety outcomes with adjuvant abemaciclib for 2 years plus ET vs ET alone in high-risk HR-positive/HER2-negative EBC (abstract 501).
• A meta-analysis of the impact of ovarian suppression on breast cancer recurrence and survival in nearly 15,000 women with breast cancer (abstract 503).
• Analysis of the SOFT trial evaluating the prognostic and predictive utility of PAM50 intrinsic subtypes and the risk of recurrence score in premenopausal women diagnosed with EBC (abstract 504).

Top Picks: Gastrointestinal Cancers
Christopher H. Lieu, MD, and Rachna T. Shroff, MD, MS, identified the following as their top abstracts to watch this year.

• NORPACT-1: randomized phase II study of short-course neoadjuvant FOLFIRINOX vs upfront surgery for patients with resectable pancreatic head cancer (abstract LBA4005); although many institutions currently use neoadjuvant CT for resectable pancreatic cancer, randomized data are quite limited; this trial will add to the knowledge of how best to treat this population of patients.
• SGNTUC-019: phase II study evaluating tucatinib plus trastuzumab for patients with previously treated HER2-positive metastatic biliary tract cancer (BTC) (abstract 4007); positive data from this study could indicate a promising targeted therapy regimen for advanced BTC and potentially support an accelerated approval for this combination.
• PROSPECT: phase III study of neoadjuvant chemoradiation vs neoadjuvant FOLFOX CT with or without chemoradiation for patients with locally advanced rectal cancer (abstract LBA2); this trial will provide valuable information regarding management of patients with rectal cancer who are undergoing total mesorectal excision.
• ATTRACTION-5: phase III study of adjuvant nivolumab plus CT vs CT alone for patients with pathological stage III gastric or gastroesophageal junction cancer who had undergone gastrectomy (abstract 4000); although it appears this study did not meet its primary relapse-free survival (RFS) endpoint, data from this trial should be very informative regarding the use of adjuvant immunotherapy for patients with resected gastroesophageal cancers.

Additional studies to watch in gastrointestinal cancers include:

• AtezoTRIBE: overall survival results and updated data from a randomized phase II study of first-line atezolizumab plus FOLFOXIRI plus bevacizumab vs FOLFOXIRI plus bevacizumab for unresectable metastatic colorectal cancer (mCRC) (abstract 3500).
• FIRE-4: analysis of RAS and BRAF status by serial liquid biopsy and associated survival outcomes in patients from the phase III trial of FOLFIRI plus cetuximab to progression vs FOLFIRI plus cetuximab followed by maintenance 5-FU/FA plus bevacizumab to progression for RAS wild-type mCRC. (abstract 3507).
• KEYNOTE-966: health-related quality of life data from the phase III study of first-line pembrolizumab plus gemcitabine/cisplatin vs gemcitabine/cisplatin for patients with advanced BTC. (abstract 4003)
• HERIZON-BTC-01: phase IIb study of the HER2-targeted bispecific antibody zanidatamab for patients with previously treated HER2-positive locally advanced unresectable or metastatic BTC (abstract 4008).

Top Picks: Genitourinary Cancers
In genitourinary cancers, long-term follow-up results are being reported for multiple key studies, including:

• KEYNOTE-426: 5-year analysis of a phase III study evaluating pembrolizumab plus axitinib vs sunitinib as first-line treatment of patients with advanced renal cell carcinoma (abstract LBA4501).
• CLEAR: phase III study of lenvatinib plus pembrolizumab vs sunitinib in advanced renal cell carcinoma (abstract 4502); at approximately 4 years of follow-up, lenvatinib plus pembrolizumab continues to demonstrate overall survival (OS) and progression-free survival (PFS) benefits and improved overall response rates (ORRs) compared with sunitinib.
• EV-103 (KEYNOTE-869): 4-year follow-up of a cohort of cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received enfortumab vedotin plus pembrolizumab as first-line therapy in a phase Ib/II study (abstract 4505); results from this trial recently led to the accelerated approval of enfortumab vedotin plus pembrolizumab by the FDA in this setting, and data presented at ASCO 2023 will report durable and rapid responses with favorable survival trends. 

Top Picks: Gynecologic Cancers
At ASCO 2023, several studies in endometrial, cervical, and ovarian cancers are being presented as late-breaking abstracts. Many other interesting studies also are being reported.

For gynecologic cancers, Lauren Prescott, MD, and Ritu Salani, MD, MBA, identified the following as the top abstracts to watch at the meeting.

Endometrial

• ENGOT-EN6-NSGO/GOG-3031/RUBY: phase III study of dostarlimab plus CT followed by dostarlimab maintenance in primary advanced or recurrent endometrial cancer (abstract 5503); results by blinded independent central review will be reported—with potential for changing the standard of care in this patient population.

Cervical

• CCTG CX.5-SHAPE: phase III trial of radical hysterectomy and pelvic node dissection compared with simple hysterectomy and pelvic node dissection in low-risk, early-stage cervical cancer (abstract LBA5511).
• Final OS results from KEYNOTE-826: phase III study of CT with or without pembrolizumab as first-line treatment for patients with persistent, recurrent, or metastatic cervical cancer (abstract 5500); results to be reported at the meeting indicate a significant reduction in the risk of death in patients with PD-L1 combined positive score ≥1.

Ovarian

• DUO-O: randomized, placebo-controlled phase III study of durvalumab plus carboplatin, paclitaxel, and bevacizumab, then maintenance bevacizumab, durvalumab, and olaparib in patients with newly diagnosed advanced ovarian cancer and no BRCA1/2 gene alteration (abstract LBA5506); data to be presented at the meeting will feature interim PFS results noted in a press release to be statistically significant and clinically meaningful compared with CT plus bevacizumab alone.
• MIRASOL: initial report from a phase III study of mirvetuximab soravtansine vs investigator’s choice of CT in platinum-resistant ovarian cancer with high expression of FRα (abstract LBA5507); results to be presented at the meeting suggest a significant survival advantage with mirvetuximab in this patient population.

An additional study to watch in gynecologic cancer includes:

• Patient-reported outcomes from the phase III ENGOT-EN6/RUBY trial of dostarlimab plus standard-of-care CT in primary advanced or recurrent endometrial cancer (abstract 5504).

Top Picks: Hematologic Malignancies
Several interesting and potentially practice-changing studies in hematologic malignancies are being reported at ASCO 2023.

Eunice S. Wang, MD, identified top abstracts to watch in the area of myelodysplastic syndromes (MDS) and leukemias at ASCO 2023.

Patients with low-risk MDS with anemia often require transfusions to raise hemoglobin levels to mitigate adverse events (ie, fatigue, dyspnea with exertion), particularly in the setting of concordant cardiovascular and pulmonary comorbidities. These patients typically have been offered erythropoiesis-stimulating agents (ESAs) to reduce transfusion dependence with low response rates. Two randomized phase III studies (COMMANDS, IMerge) represent significant advances for this patient population.

• COMMANDS trial efficacy and safety results: randomized phase III study evaluating luspatercept vs epoetin alfa in patients with ESA‑naive, transfusion-dependent lower‑risk MDS (abstract 7003). The COMMANDS trial establishes that administration of luspatercept results in clinically meaningful and statistically significant improvements in red blood cell transfusion needs with durable responses compared with ESAs, thereby establishing a new standard-of-care growth factor to address, reduce, and prevent transfusion needs in patients with lower-risk MDS with newly diagnosed anemia.
• IMerge: results from a randomized, double-blind, placebo-controlled phase III study of imetelstat in patients with heavily transfusion‒dependent, non-del(5q), lower-risk MDS relapsed/refractory (R/R) to ESAs (abstract 7004). The results of IMerge address patients with lower-risk MDS who already are heavily dependent on red blood cell transfusions but have not yet received hypomethylating agent therapy. For these patients, the use of the telomerase inhibitor imetelstat appears to alter the natural progression of disease, as demonstrated by decreased transfusion dependence, reduction of mutant allele frequency associated with underlying MDS, and prolonged duration of transfusion independence.
• Alliance A041703: CT-free treatment with inotuzumab ozogamicin and blinatumomab for older adults with newly diagnosed Ph-negative, CD22-positive, B-cell acute lymphoblastic leukemia (ALL) (abstract 7006). Although typically considered a pediatric cancer, ALL is increasingly being diagnosed in older individuals (60 years of age and older) who are poor candidates for the high-dose intensive multiagent CT regimens used with such success in younger patients. For these individuals, the results of this phase II trial of 2 antibody-based therapies—inotuzumab ozogamicin (anti-CD22 ADC) and blinatumomab (bispecific CD19/CD3 antibody)—offer the potential of a traditional “CT-free” strategy. Although tested in only 33 patients to date, this regimen resulted in high response rates of 85% to 97% after 1-2 cycles of therapy, with 84% of patients alive 1 year after diagnosis.

In multiple myeloma (MM), Shaji Kumar, MD, identified the following abstracts to watch. 

• CARTITUDE-4: phase III study of cilta-cel vs PVd or DPd in MM for individuals who have received 1-3 lines of prior therapy and who are lenalidomide refractory (abstract LBA106). Data to be reported at ASCO 2023 will include comparative PFS between cilta-cel and standard-of-care therapy for lenalidomide-refractory disease.
• CARTITUDE-1: phase Ib/II study of cilta-cel in R/R MM (abstract 8009). The final results from this trial confirm the median PFS of nearly 3 years with cilta-cel, without long-term adverse events compared with previous reports.
• MajesTEC-1: extended follow-up from the phase Ib/II study of teclistamab, a BCMA-targeted bispecific antibody, in R/R MM (abstract 8011). With 22 months of follow-up, these findings confirm the long-term efficacy data with teclistamab, with a median PFS of 1 year. Potential long-term toxicities will be reported.
• MagnetisMM pooled analysis: phase I/II studies of elranatamab, a BCMA-targeted bispecific antibody, in R/R MM (abstract 8008). The results to be reported at ASCO 2023 indicate significant activity of elranatamab among patients with prior exposure to anti-BCMA therapies. Most received a previous BCMA-targeted ADC, and 42% had received CAR T-cell therapy. Although the response rates are lower, they still seem meaningful.
• PHE885 in R/R MM: phase I study of a BCMA-targeted CAR T-cell therapy with a novel manufacturing process that reduces manufacturing time and potentially prolongs CAR T-cell persistence (abstract 8004). Previous results showed responses deepening over time. The updated safety and clinical response data are to be reported at ASCO 2023.

For lymphomas, Jeff Sharman, MD, has identified multiple abstracts of special interest to look for at ASCO 2023.

• SWOG S1826: results from the phase III trial of AVD in combination with either nivolumab or BV in advanced-stage classical Hodgkin lymphoma (abstract LBA4). ABVD was the standard of care for decades in patients with advanced-stage classical Hodgkin lymphoma. In 2018, the ECHELON-1 trial demonstrated the superiority of AVD plus BV over ABVD and has become the standard of care for these patients. In 2015, we had the first reports of the efficacy of immune checkpoint inhibitors in patients with R/R Hodgkin lymphoma, but now we will see if AVD is better with the addition of an immune checkpoint inhibitor vs BV.
• Updated results and landmark analysis of data from a phase II study of glofitamab monotherapy in patients with R/R large B-cell lymphoma (abstract 7550). At ASCO 2023, we will be hearing a lot about bispecific antibodies. Results from several studies of glofitamab and epcoritamab will be presented. Very recently, epcoritamab received FDA approval in R/R diffuse large B-cell lymphoma (May 19, 2023), and glofitamab is expected to be approved soon in the United States. At ASCO 2023, updated results from a pivotal phase II study of glofitamab monotherapy in large B-cell lymphoma will be presented. The most exciting aspect of the dataset is that with fixed duration of therapy, patients who achieved a complete response can remain in sustained remission without additional therapy.
• BRUIN: longer-term efficacy and safety results from the phase I/II study of pirtobrutinib among patients with mantle-cell lymphoma (MCL) who have been previously treated with a covalent BTK inhibitor (abstract 7514). BTK inhibitors have transformed the management of multiple lymphoid malignancies. Many patients with R/R MCL will receive a covalent BTK inhibitor such as ibrutinib, acalabrutinib, or zanubrutinib. When disease relapse occurs with a covalent BTK inhibitor, the standard of care becomes less clear. Pirtobrutinib, a noncovalent BTK inhibitor, recently received FDA approval in this space. Mature data from the BRUIN trial demonstrated a median PFS of 7.4 months and a median OS of 23.5 months. Among responding patients, the median duration of response was 17.6 months, and the ORR was 57%.
• TRANSCEND CLL 004: primary analysis of the efficacy and safety of liso-cel in patients with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (abstract 7501).
• JACKPOT8: primary analysis of the efficacy and safety results from a phase II trial of the JAK1 inhibitor golidocitinib in patients with R/R peripheral T-cell lymphoma. (abstract 7503)
• EPCORE NHL-1: updated efficacy and safety results from a long-term follow-up of patients with R/R large B-cell lymphoma who received SC epcoritamab. (abstract 7525)

Additional studies to watch in hematologic malignancies include:

• A post hoc analysis of cardiotoxicity associated with CPX-351 vs 7+3 induction therapy from the comparative phase III trial in patients with previously untreated high-risk acute myeloid leukemia. (abstract 7029)
• KEYNOTE-667: preliminary findings from the phase II trial of pembrolizumab plus CT in children and young adults with newly diagnosed classical Hodgkin lymphoma and slow early response to upfront CT (abstract 10027).

Top Picks: Lung Cancer
In lung cancer, Karen Reckamp, MD, and Heather Wakelee, MD, FASCO, have identified several late-breaking abstracts of interest at ASCO 2023, along with many other interesting studies being reported.

• ADAURA: OS data from the phase III trial evaluating adjuvant osimertinib in patients with resectable stage IB-IIIA, EGFR-mutated non-small-cell lung cancer (NSCLC) (abstract LBA3). Adjuvant osimertinib became the standard of care for patients with resected EGFR-mutated NSCLC based on the disease-free survival benefit shown in initial reports from ADAURA. However, considering previous trials with first-generation EGFR tyrosine kinase inhibitors (TKIs), many wondered if this would translate into an OS benefit for these patients. At ASCO 2023, we anticipate report of an OS benefit with adjuvant osimertinib, which we hope will lead to increased use of adjuvant osimertinib in this setting and improved outcomes for patients with resected EGFR-mutated NSCLC.
• KEYNOTE-671: phase III trial evaluating neoadjuvant pembrolizumab or placebo plus CT followed by resection and pembrolizumab or placebo in patients with early-stage NSCLC (abstract LBA100). The use of immunotherapy and combination therapy in the perioperative setting has been established by the CheckMate 816 and AEGEAN trials, but the addition of adjuvant immunotherapy following neoadjuvant therapy is somewhat controversial. The results of KEYNOTE-671 will help clarify the utility of both neoadjuvant and adjuvant immunotherapy for early-stage NSCLC.
• LUNAR: phase III trial evaluating tumor-treating field therapy in combination with standard-of-care therapy for the treatment of metastatic NSCLC (abstract LBA9005). At ASCO 2023, we anticipate report of an OS benefit, irrespective of driver mutation, with this novel approach.

Additional studies to watch in lung cancer include:

• KEYNOTE-789: phase III trial of pemetrexed plus platinum-based CT with or without pembrolizumab for EGFR-mutated, TKI-resistant, metastatic nonsquamous NSCLC (abstract LBA9000).
• AGAIN (JCOG1404/WJOG8214L): phase III trial evaluating EGFR TKI monotherapy vs combination therapy with an EGFR TKI plus pemetrexed and cisplatin in the treatment of newly diagnosed EGFR-mutated advanced nonsquamous NSCLC (abstract LBA9009).
• TROPION-Lung02: update of phase Ib study evaluating datopotamab deruxtecan plus pembrolizumab with or without platinum-based CT for the treatment of advanced NSCLC (abstract 9004).
• Interim report of phase II study evaluating combination therapy with tepotinib plus osimertinib for EGFR-mutated advanced NSCLC with MET amplification following first-line osimertinib (abstract 9021).
• CheckMate 9LA: 4-year update of phase III trial evaluating combination therapy with nivolumab and ipilimumab plus CT vs CT alone in metastatic NSCLC, including results by tumor histologic subtype (abstract LBA9023).
• NEOTORCH: interim report of phase III trial evaluating perioperative toripalimab plus platinum-doublet CT vs CT alone in resectable stage II/III NSCLC (abstract 8501).
• Phase II study evaluating neoadjuvant osimertinib in the management of resectable EGFR-mutated NSCLC (abstract 8508).
• SWOG S1929: randomized phase II trial of maintenance atezolizumab plus talazoparib vs atezolizumab monotherapy in SLFN11-expressing extensive-stage small-cell lung cancer (abstract 8504).
• IND227: phase III trial of pemetrexed and cisplatin with or without pembrolizumab for malignant pleural mesothelioma (abstract LBA8505).

Top Picks: Skin Cancer
Jason Luke, MD, FACP, and Jeffery S. Weber, MD, PhD, have identified several key studies of interest at ASCO 2023.

• mRNA-4157-P201/KEYNOTE-942: phase II study of personalized neoantigen mRNA vaccine plus pembrolizumab vs pembrolizumab in advanced melanoma (abstract LBA9503). Previous results showed an improvement in RFS with the mRNA vaccine. The distant metastasis‒free survival (DMFS) data are to be reported at ASCO 2023 and are anticipated to further demonstrate the potential of this therapy.
• KEYNOTE-716: final DMFS from the phase III trial of adjuvant pembrolizumab vs placebo in stage IIB or IIC melanoma (abstract LBA9505). KEYNOTE-716 established the role of adjuvant therapy in stage IIB/C melanoma. These data inform the long-term benefit of adjuvant therapy, and it will be important to see how the data mature and whether the benefit for patients increases over time, especially by substage.
• Fianlimab plus cemiplimab in advanced melanoma: phase I study (abstract 9501) of the combination of an anti‒LAG-3 antibody and an anti‒PD-1 antibody different from the combination used in RELATIVITY-047. Updated data include evidence of efficacy in a cohort of patients who received adjuvant anti‒PD-1 therapy. These data suggest this combination may have an ORR advantage over currently approved anti‒LAG-3/anti‒PD-1 therapy.
• RELATIVITY-047: 2-year update on efficacy from the phase I/II trial of relatlimab plus nivolumab vs nivolumab as frontline therapy in advanced melanoma (abstract 9502). This update offers more encouraging data on OS from the first approved anti‒LAG-3/anti‒PD-1 combination therapy.
• CheckMate 76K: analysis of biomarker association with efficacy with adjuvant nivolumab (abstract 9504). Adjuvant therapy for stage IIB/IIC has become a standard-of-care option in melanoma, yet the risk of overtreatment remains, and currently no biomarker data inform patient selection. These data to be reported will help inform those considerations.

Additional studies to watch in skin cancer include:

• PRADO and OpACIN-neo: 3-year update on long-term survival post neoadjuvant ipilimumab plus nivolumab in stage III melanoma (abstract 101).
• Subgroup analysis of fianlimab plus cemiplimab in patients with poor prognosis from a phase I study (abstract 9548).