Conference Compendium: The Top 10 Takeaways From ESMO 2024

Data from the phase 2 WSG-TP II trial (NCT03272477) showed that combining neoadjuvant endocrine therapy or chemotherapy with trastuzumab and pertuzumab elicited “exceptionally excellent” survival outcomes among patients with hormone receptor–positive, HER2-positive early breast cancer.

At the 2024 European Society of Medical Oncology (ESMO) Congress, researchers from across the world gathered to present updated findings on various anti-cancer treatment modalities for several different patient populations. Specifically, many oral presentations from the meeting focused on therapeutic strategies that have the potential to improve outcomes across the breast and lung cancer fields.

CancerNetwork^® covered the breaking data across these disciplines. Here are the top 10 articles covering the latest data from this year’s ESMO Congress that may impact the treatment paradigm:

#1: Neoadjuvant ET And De-Escalated Chemotherapy Lead to ‘Exceptionally Excellent’ Survival in HR+/HER+ Early Breast Cancer

Data from the phase 2 WSG-TP II trial (NCT03272477) showed that combining neoadjuvant endocrine therapy or chemotherapy with trastuzumab (Herceptin) and pertuzumab (Perjeta) elicited “exceptionally excellent” survival outcomes among patients with hormone receptor (HR)–positive, HER2-positive early breast cancer.¹ With a median follow-up of 60 months, the 5-year event-free survival (EFS) rates with endocrine therapy or chemotherapy plus trastuzumab/pertuzumab, respectively, were 92.1% and 94.8% (HR, 1.29; 95% CI, 0.26-2.32; P = .65). Investigators concluded that both treatment arms demonstrated “excellent outcomes” in HR-positive, HER2-positive disease.

#2: Ribociclib Combo Yields Extended iDFS Benefit in HR+/HER2– Breast Cancer

According to 4-year landmark analysis data from the phase 3 NATALEE trial (NCT03701334), combination therapy with ribociclib (Kisqali) plus nonsteroidal aromatase inhibitor (NSAI) therapy yielded enduring invasive disease-free survival (iDFS) improvements compared with NSAI alone in patients with HR-positive, HER2-negative breast cancer.² In the ribociclib/NSAI and NSAI alone arms, respectively, the 3-year iDFS rates were 90.8% vs 88.1%, and the 4-year rates were 88.5% vs 83.6% (HR, 0.715; 95% CI, 0.609-0.840; P <.0001).

These updated findings supported the recent FDA approval of ribociclib plus an aromatase inhibitor for those with HR-positive, HER2-negative stage II or III early breast cancer at high risk of recurrence.³

#3: Belrestotug/Dostarlimab Improves ORR in PD-L1–High NSCLC

Based on data from the phase 2 GALAXIES-Lung 201 study (NCT05565378), combining belrestotug (formerly EOS 448) with dostarlimab-gxly (Jemperli) resulted in a clinically meaningful objective response rate (ORR) improvement vs dostarlimab alone in patients with previously untreated, unresectable, locally advanced or metastatic, PD-L1–high non–small cell lung cancer (NSCLC).⁴ ORRs in the combination therapy arm included 63.3% (95% CI, 43.9%-80.1%), 65.6% (95% CI, 46.8%-81.4%), and 76.7% (95% CI, 57.7%-90.1%) when belrestotug was administered at 100 mg (n = 30), 400 mg (n = 32), and 1000 mg (n = 30), respectively.

#4: Hypofractionated Radiation Noninferior to Normofractionated Radiation in Early Breast Cancer

Investigators of the phase 3 HypoG-01 trial (NCT03127995) noted non-inferior outcomes with moderately hypofractionated, locoregional radiotherapy compared with normofractionated radiotherapy when mitigating the risk of lymphedema in those with early breast cancer.⁵ At 5 years, the rate of lymphedema with hypofractionated radiation was 33.3% (95% CI, 28.7%-38.4%) compared with 32.8% (95% CI, 27.9%-38.1%) among patients who received normofractionated radiotherapy.

#5: OS Increase Observed in Neoadjuvant Pembrolizumab Combo Plus Adjuvant Therapy in Early TNBC

A perioperative regimen consisting of pembrolizumab (Keytruda) and chemotherapy elicited a statistically significant improvement in overall survival (OS) among patients with early-stage triple-negative breast cancer (TNBC) in the phase 3 KEYNOTE-522 trial (NCT03036488).⁶ In patients who received perioperative pembrolizumab plus chemotherapy vs those who were treated with placebo/chemotherapy, the risk of death decreased by 34% (HR, 0.66; 95% CI, 0.50-0.87; P = .00150).

#6: Breastfeeding Is Feasible Amid Endocrine Therapy Break in HR+ Breast Cancer

Follow-up data from the POSITIVE trial (NCT02308085) demonstrated the feasibility of breastfeeding for patients with HR-positive breast cancer who conceived during a break from endocrine therapy.⁷ Findings from this study “underline the interest of young breast cancer survivors in breastfeeding and reinforce the notion that breastfeeding counseling should be incorporated into their individualized support,” according to study author Fedro Peccatori, MD, PhD, director of the Fertility and Procreation Unity in the Division of Gynecologic Oncology in the Department of Gynecology at the European Institute of Oncology in Milan, Italy.

#7: Pembrolizumab/CRT Improve Survival in High-Risk Locally Advanced Cervical Cancer

Combining pembrolizumab with chemoradiotherapy (CRT) showed a statistically significant and clinically meaningful survival improvement compared with CRT alone among patients with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer who were assessed as part of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945).⁸ At 36 months, the OS rate was 82.6% (95% CI, 78.4%-86.1%) in the pembrolizumab/CRT arm vs 74.8% (95% CI, 70.1%-78.8%) in the CRT alone arm (HR, 0.67; 95% CI, 0.50-0.90; P = .0040).

#8: Adjuvant Durvalumab Does Not Improve DFS Across NSCLC PD-L1 Subgroups

Adjuvant durvalumab (Imfinzi) given after complete resection and optional chemotherapy did not confer disease-free survival (DFS) improvements compared with placebo among patients with EGFR- or ALK-negative NSCLC of varying PD-L1 expression statuses in the phase 3 BR.31 trial (NCT02273375).⁹ Findings from this trial suggest that “the presence of primary disease and associated tumor antigens, as in the perioperative approach, may be required for optimal efficacy” in this population, according to study author Glenwood Goss, MB, BCh, FCPSA, FRCPC, a professor of medicine in the University of Ottawa Division of Medical Oncology, a chair of the Thoracic Oncology Site Committee, and director of Clinical and Translational Research at Ottawa Hospital Cancer Centre.

#9: Addition of Capivasertib to Paclitaxel Fails to Improve OS in Metastatic TNBC

In the phase 3 CAPItello-290 trial (NCT03997123), adding capivasertib (Truqap) to paclitaxel as frontline therapy did not improve OS among patients with metastatic TNBC.¹⁰ Across the overall population, the median OS was 17.7 months (95% CI, 15.6-20.3) with capivasertib plus paclitaxel vs 18.0 months (95% CI, 15.3-20.3) with placebo (HR, 0.92; 95% CI, 0.78-1.08; P = .3239).

#10: Belzutifan Yields Sustained Responses, PFS in Advanced Clear Cell RCC

Final analysis data showed that outcomes including ORR and progression-free survival (PFS) improved with belzutifan (Welireg) vs everolimus (Afinitor) among patients with previously treated advanced renal cell carcinoma (RCC) in the phase 3 LITESPARK-005 trial (NCT04195750).¹¹ The median PFS was 5.6 months (95% CI, 3.8-6.5) and 5.6 months (95% CI, 4.8-5.8) in the belzutifan and everolimus arms, respectively (HR, 0.75; 95% CI, 0.63-0.88).

References

1. Gluz O, Nitz UA, Christgen M et al. Survival outcome of neoadjuvant endocrine therapy + trastuzumab and pertuzumab (ET+T+P) vs. de-escalated chemotherapy (CT)+T+P in hormone receptor positive (HR+)/HER2+ early breast cancer (EBC): WSG-TP-II trial. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA17.
2. Fasching PA, Stroyakovskiy D, Yardley DA, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with HR+/HER2– early breast cancer: 4-year outcomes from the NATALEE trial. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. LBA13.
3. FDA approves Novartis Kisqali® to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed September 18, 2024. https://shorturl.at/p0jbc
4. Spigel DR, Korbenfeld E, Hayashi H, et al. Interim analysis of GALAXIES Lung-201: phase 2, randomized, open-label platform study of belrestotug plus dostarlimab in patients with previously untreated locally advanced/metastatic PD-L1 high (TPS ≥50%) non-small cell lung cancer. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Presentation LBA52.
5. Rivera S, Ghodssighassemabadi R, Brion T, et al. Locoregional hypo vs normofractionated RT in early breast cancer: 5 years results of the HypoG-01 phase I UNICANCER trial. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 231O
6. Schmid P, Cortes J, Dent R, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: overall survival results from the phase III KEYNOTE-522 study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA4.
7. Azim HA, Niman SM, Partridge AH, et al. Breastfeeding in women with hormone receptor-positive breast cancer who conceived after temporary interruption of endocrine therapy results from the POSITIVE trial. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. 1814O.
8. Lorusso D, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Presented at: 2024 ESMO Congress; September 12-17, 2024; Barcelona, Spain. Presentation 7090.
9. Goss G. CCTG BR.31: a double-blind placebo-controlled randomized phase 3 trial of adjuvant durvalumab in completely resected non-small cell lung cancer. Presented at the 2024 European Society of Medical Oncology (ESMO) Congress, Barcelona, Spain; September 13-17, 2024. LBA48.
10. Schmid P, McArthur H, Cortes J, et al. Capivasertib + paclitaxel as first-line treatment of metastatic triple-negative breast cancer: the CAPItello-290 Phase 3 trial. Presented at: ESMO Congress 2024; September 12-16, 2024; Barcelona, Spain. Abstract LBA19.
11. Rini B, Suarez C, Albiges L, et al. Final analysis of the phase 3 LITESPARK-005 study of belzutifan versus everolimus in participants with previously treated clear cell renal cell carcinoma. Presented at: ESMO Congress 2024; September 13-17, 2024; Barcelona, Spain. Abstract LBA74.