An Expert’s Guide to ESMO 2022: A Preview of the Top Abstracts

During the 2022 European Society for Medical Oncology (ESMO) Congress, exciting and important results from many clinical trials will be reported. In this commentary, oncology experts have highlighted the abstracts they are most looking forward to seeing presented at the meeting. We will cover these abstracts in more detail as part of Clinical Care Options’ (CCO) independent conference coverage of the 2022 ESMO Congress. As the meeting unfolds, remember to check the CCO website for downloadable slidesets, including the data from these highlighted studies and more. After the conference, check out the CME-certified expert analysis text module with perspectives and clinical implications of these new data.

Top Picks: Breast Cancers and Gynecologic Cancers
In metastatic breast cancer, Sara Tolaney, MD, MPH, identified several studies with the potential to change practice, including the following:

• A highly anticipated, late-breaking abstract from the phase III TROPICS-02 study of sacituzumab govitecan, an antibody–drug conjugate targeting TROP2 with an SN38 cytotoxic payload, vs treatment of physician’s choice in patients with hormone receptor–positive/HER2-negative metastatic breast cancer (abstract LBA76), including an efficacy analysis by HER2 immunohistochemistry status (abstract 214MO). Of note, single-agent chemotherapy has limited utility in this setting. The TROPICS-02 study was reported to have met its primary endpoint of progression-free survival (PFS) at the 2022 American Society of Clinical Oncology Annual Meeting, and the secondary overall survival (OS) endpoint results will be presented at the ESMO meeting, which, based on an earlier press release, were statistically significant and clinically meaningful. These data are important for establishing sacituzumab govitecan as a new treatment option for pretreated patients with hormone receptor–positive disease.
• The interim OS results from phase III MONARCH 3 of abemaciclib plus a nonsteroidal aromatase inhibitor in patients with hormone receptor–positive/HER2-negative advanced breast cancer (abstract LBA15). Although there are 3 CDK4/6 inhibitors available, and with similar and clinically significant improvements in PFS, there are differences in OS benefit in the first-line setting, for example, with a significant OS benefit seen with ribociclib but not with palbociclib. Data to be presented at ESMO will be critical to our understanding of whether abemaciclib could potentially yield an improvement in OS in this setting.

Additional studies to watch include:

• First results from the multicohort phase II BELLINI trial of nivolumab in combination with ipilimumab in patients with early-stage triple-negative breast cancer with tumor-infiltrating lymphocytes (abstract LBA13).

In gynecologic cancers, Nicoletta Colombo, MD, PhD, selected the following as her top abstracts to watch at the meeting:

• OS results after 7 years of follow-up for patients with newly diagnosed advanced ovarian cancer who were treated with maintenance olaparib vs placebo in the phase III GOG-3004/SOLO-1 trial (abstract 517O). Data to be presented at the meeting will show that 2 years of maintenance olaparib at the end of front-line chemotherapy in patients with BRCA mutation improve OS compared with placebo even after a significant proportion of patients (>40%) in the placebo group went on to receive a subsequent PARP inhibitor. These 7-year results will provide further confirmation of the benefit of maintenance olaparib, without new safety signals identified.
• The phase III ENGOT-ov25/PAOLA-1 trial of maintenance therapy with olaparib with bevacizumab vs bevacizumab alone in women with newly diagnosed advanced ovarian cancer. The addition of maintenance olaparib to bevacizumab provided a significant and clinically meaningful OS benefit to patients who were homologous recombinant deficiency (HRD) positive (5-year OS rate: 65.5% vs 48.4%; HR: 0.62; 95% CI: 0.45-0.85), despite a high proportion of patients in the bevacizumab control arm receiving a PARP inhibitor post progression. At ESMO this year, we will see the final OS results from the phase III ENGOT-ov25/PAOLA-1 trial of maintenance therapy with olaparib with bevacizumab vs bevacizumab alone in women with newly diagnosed advanced ovarian cancer (abstract LBA29). Data from this analysis will continue to add support for the addition of olaparib to bevacizumab as a standard of care for HRD-positive ovarian cancer treated in the frontline setting. 

Top Picks: Genitourinary Cancers
In renal cell carcinoma (RCC), Robert Motzer, MD, identified the following key abstracts at the meeting:

• Results from the randomized phase III CheckMate 914 trial of 6-month adjuvant treatment with nivolumab plus ipilimumab vs placebo in patients with localized RCC at high risk of relapse following nephrectomy. Data to be presented at the meeting indicate that the primary endpoint of disease-free survival was not met for nivolumab plus ipilimumab compared with placebo. This differs from a recent report on the KEYNOTE-564 trial, which showed disease-free survival benefit for 1 year of pembrolizumab compared with placebo. Experts suggest that differences in study design, patient population, tolerability, and drug exposure could be plausible explanations for this difference (abstract LBA4).
• Results from the multicenter, randomized, active-controlled phase III COSMIC-313 study of cabozantinib in combination with nivolumab and ipilimumab vs standard of care treatment with nivolumab and ipilimumab in previously untreated intermediate/poor-risk advanced RCC will be presented (abstract LBA8). The study was reported to have met its coprimary endpoint of PFS but not OS at a prespecified interim analysis; positive results from this combination at ESMO may expand treatment options for patients with advanced kidney cancer.

In urothelial cancers, Elizabeth Plimack, MD, MS, identified the following key abstracts at the meeting:

• The first report from cohort K of the phase I/IIb EV-103/KEYNOTE-869 study of enfortumab vedotin alone or in combination with pembrolizumab in previously untreated, cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (abstract LBA73). Positive topline results were previously announced for the primary endpoint of overall response rate (ORR) in mid-2022 and are expected to be presented at the meeting. Additional data on how long to continue therapy in this setting following an excellent response, and whether this combination might also be an option for cisplatin-eligible patients, are of clinical interest.

Additional studies to watch include:

• Phase III CheckMate 274: tumor and immune features associated with disease-free survival following adjuvant nivolumab in patients with high-risk muscle-invasive urothelial carcinoma following radical resection (abstract 1737MO).

Top Picks: Cholangiocarcinoma/Hepatocellular Carcinoma
Rachna Shroff, MD, identified key abstracts at the meeting likely to inform future trial development for cholangiocarcinoma and liver cancer:

• In FGFR inhibitor–naive cholangiocarcinoma, Hollebecque and colleagues report the efficacy results from the phase I/II ReFocus trial of RLY-4008, a highly selective, next-generation FGFR2 inhibitor, in patients with FGFR2 fusion or rearrangements having received previous standard therapy, including chemotherapy (abstract LBA12). The primary endpoints include ORR per Response Evaluation Criteria in Solid Tumors, the maximum tolerated dose, and safety. Healthcare professionals hope for positive results from this trial and that a next-generation, FGFR2- inhibitor like RLY-4008 may circumvent resistance mechanisms previously seen with other FGFR2 inhibitors.
• The anticipated primary results from the phase III LEAP-002 study of lenvatinib with or without pembrolizumab as first-line treatment for patients with advanced hepatocellular carcinoma (HCC) (abstract LBA34). This study was previously reported to have failed its dual primary endpoints of OS and PFS. However, data to be presented at the meeting will show there was a trend toward improvement for the combination compared with lenvatinib monotherapy. Based on these data, the combination of bevacizumab and atezolizumab remains the treatment of choice for advanced HCC.

Top Picks: Lung Cancers
In lung cancer, David Planchard, MD, PhD, selected some of the key studies he is looking forward to at the meeting:

• Data from the phase III CodeBreaK 200 study of sotorasib vs docetaxel for patients with previously treated non-small-cell lung cancer (NSCLC) and a KRAS^G12C mutation (abstract LBA10). Sotorasib has previously been shown to provide antitumor activity and a manageable safety profile, for which it received FDA accelerated approval in this setting. 

• Mature disease-free survival data from the phase III ADAURA trial of osimertinib as adjuvant therapy in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC (abstract LBA47). The presentation at ESMO will show data for 2 additional years of follow-up, including patterns of recurrence and central nervous system disease-free survival in patients with early-stage lung cancer. Of note, osimertinib is the only FDA-approved targeted therapy in this disease setting.

Additional studies to watch include:

• Interim results from the phase II DESTINY-Lung02 trial of trastuzumab deruxtecan in patients with HER2-mutated metastatic NSCLC who have progressed following 1 or more systemic therapies (abstract LBA55).
• Phase III CheckMate 816: analysis of pathological features and efficacy outcomes with neoadjuvant nivolumab with platinum-doublet chemotherapy in patients with resectable NSCLC (abstract LBA50).

Additional Studies of Interest in Melanoma Include:

• A retrospective study evaluating the association of pretreatment circulating tumor DNA with disease recurrence and clinical and translational factors from the phase III CheckMate 915 evaluating adjuvant nivolumab plus ipilimumab vs nivolumab alone in 1127 patients with stage IIIB-D/IV melanoma (abstract 788O).
• Additional response outcomes from the phase II/III RELATIVITY-047 study of nivolumab plus relatlimab vs nivolumab in previously untreated metastatic or unresectable melanoma (abstract 817P).
• Phase II SWOG S1801: a randomized study of adjuvant vs neoadjuvant therapy with pembrolizumab in patients with histologically confirmed, measurable, clinically detectable and resectable stage IIIB-IV cutaneous, acral and mucosal melanomas without brain metastasis (abstract LBA6).

Remember to check the CCO website often during and after ESMO!
Downloadable slideset summaries of these studies and more will be available on the CCO website as the data are released. After ESMO, comprehensive analyses by our expert faculty will explore the clinical implications of the data in a CME-certified, text-based module.