Catch up on highlights from the 2022 ASCO Congress

Highlights from ASCO 2022 

Read our highlight articles to catch up on the discussions from the American Society of Clinical Oncology (ASCO) 2022 annual meeting. Get updated on:  

• The latest results from pivotal clinical trials
• Precision medicine for stage II colon cancer
• Emerging therapies for HR+/HER2- advanced breast cancer

Day One Highlights: Emerging developments in NSCLC and HER2+ mBC

By Dawn O’Shea

It was a busy first day at ASCO 2022, with presentations on a wide range of topics, including sequencing therapy, emerging treatments, and the evolving role of molecular testing.

Treatment of patients with advanced NSCLC

One of the main sessions of the day focused on emerging developments in the treatment of non-small cell lung cancer (NSCLC).

Dr Alexander Spira from the Virginia Cancer Specialists Research Institute presented the results from a registrational Phase 2 cohort of the KRYSTAL-1 trial (NCT03785249) which examined the efficacy and safety of the differentiated KRAS^G12C inhibitor, adagrasib, for the treatment of patients with advanced/metastatic NSCLC harbouring a KRAS^G12C mutation. Adagrasib is currently being reviewed for authorisation by the Federal and Drug Administration (FDA) and has been submitted to the European Medicines Agency (EMA) for this indication¹.

The trial found that adagrasib achieved an objective response rate of 43% (95% CI, 33.5–52.6) and a disease control rate of 80% (95% CI, 70.8–86.5) in patients with previously-treated NSCLC with a KRAS^G12C mutation (n = 112). However, grade 3–4 treatment-related adverse events occurred in 43% of patients¹.

Data from a Phase 1b cohort suggest that adagrasib penetrates the central nervous system (CNS), although this is based on the outcomes of just two patients with active untreated CNS metastases. Both patients experienced regression of the metastases¹.

Meanwhile, Dr Oladimeji Akinboro presented the findings of retrospective exploratory pooled analyses of data from randomised controlled trials that supported FDA approvals on outcomes with anti-PD-L1 treatment with or without chemotherapy as first-line treatment for advanced NSCLC with PD-L1 expression ≥50%. Patients received chemotherapy and immunotherapy, immunotherapy alone or chemotherapy alone².

The analysis suggests that there may be no significant difference in overall survival for chemotherapy plus immunotherapy versus immunotherapy alone in patients with advanced/metastatic NSCLC with high PD-L1 levels, although there appeared to be a slight numerical advantage favouring the combination treatment².

Of particular note was the finding that in patients aged 75 years or older, overall survival (OS) and progression-free survival (PFS) outcomes were better with immunotherapy alone².

HER2-positive metastatic breast cancer

In an afternoon session on the management of HER2-overexpressing metastatic breast cancer (mBC), Dr Nancy Lin from the Dana-Farber Cancer Institute reviewed the latest data on the role of tyrosine kinase inhibitors (TKIs), monoclonal antibodies (mABs) and antibody drug conjugates (ADCs)³.

She highlighted the findings of the pivotal HER2CLIMB trial, which showed that tucatinib plus trastuzumab plus capecitabine achieved clinically meaningful improvements in PFS and OS, in patients with brain metastases (BM) compared to trastuzumab and capecitabine alone. Tucatinib was associated with a dramatic absolute improvement in median OS of 9.1 months³.

Tucatinib is just one of the TKIs under investigation, with Dr Lin highlighting the Phase 2 PERMEATE trial of pyrotinib and capecitabine, which found an intracranial objective response rate (ORR) of 74.6% in radiotherapy-naive patients but just 42.1% in patients with progressive disease after radiotherapy. The results suggest promising activity of pyrotinib plus capecitabine against BM, especially for the radiotherapy-naive population³.

Evidence on mABs and ADCs suggest these agents also have activity against brain metastases in patients with mBC, Dr Lin said. She presented data from the PATRICIA trial of high dose trastuzumab and pertuzumab in patients with progressive brain metastases. The study found that increasing the trastuzumab dose by 6 mg/kg IV once weekly was associated with improved intracranial responses. Compared to the standard trastuzumab-pertuzumab schedule, high-dose trastuzumab with pertuzumab achieved a clinical benefit rate of 68% at four months and 51% at six months³.

Dr Lin said, given the benefit seen with increasing the dose of trastuzumab, it is expected that ADCs may improve the benefit further since they actively deliver the treatment to the tumour. A number are under investigation³.

Dr Lin concluded by saying that multiple CNS-active agents are emerging for patients with mBC and BM, highlighting the need to include patients with CNS metastases in clinical trials³.

References

1. Spira AI, Riely GJ, Gadgeel SM, Heist RS, Ou S-HI, Pacheco JM, et al. KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced/metastatic non–small cell lung cancer (NSCLC) harboring a KRASG12C mutation. Presented at the ASCO Annual Meeting 2022, 3 June. Chicago, IL, USA. 9002. Available at: https://meetings.asco.org/abstracts-presentations/208088. Accessed 7 June 2022.
2. Akinboro O. Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis. Presented at the ASCO Annual Meeting 2022, 3 June. Chicago, IL, USA. 9000. Available at: https://meetings.asco.org/abstracts-presentations/208075. Accessed 7 June 2022.
3. Lin NU. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Presented at the ASCO Annual Meeting 2022, 4 June 2022. Chicago, IL, USA. 1005. Available at: https://meetings.asco.org/abstracts-presentations/185141. Accessed 7 June 2022.
4. Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, et al. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. Presented at the ASCO Annual Meeting 2022, 4 June. Chicago, IL USA. LBA1001. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA1001. Accessed 10 June 2022.
5. Tie J, Cohen J, Lahouel K, Lo SN, Wang Y, Wong R, et al. Adjuvant chemotherapy guided by circulating tumor DNA analysis in stage II colon cancer: The randomized DYNAMIC trial. Presented at the ASCO Annual Meeting 2022, 4 June. LBA100. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA100. Accessed 10 June 2022.
6. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. Presented at the ASCO Annual Meeting 2022, 5 June. LBA3. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA3. Accessed 10 June 2022.
7. Yoshino T, Watanabe J, Shitara K, Yasui H, Ohori H, Shiozawa M, et al. Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial. Presented at the Journal of Clinical Oncology 2022, 5 June. LBA1. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA1. Accessed 10 June 2022.
8. McCabe M, Kirton L, Khan M, Fenwick N, Strauss SJ, Valverde C, et al. Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). Presented at the ASCO Annual Meeting 2022, 5 June. LBA2. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.17_suppl.LBA2. Accessed 10 June 2022.