Catch up on highlights from the 2022 ASCO Congress

Day Four & Five Highlights: Novel developments in breast, ovarian and prostate cancer

By Dawn O’Shea

Omittance of radiotherapy in luminal A breast cancer

On the penultimate day of ASCO 2022, Dr Timothy Whelan, professor of oncology at McMaster University in Canada, presented the findings of the LUMINA trial⁹, a prospective trial omitting radiotherapy after breast-conserving surgery in women with T1N0 luminal A cancer. 

LUMINA enrolled women aged 55 years or older with T1N0 grade 1-2 HER2-negative breast cancer, with oestrogen receptor ≥1% and progesterone receptor >20%, who were post-lumpectomy. All patients underwent Ki-67 testing. Those with Ki-67 >13.25% proceeded with standard treatment. Those with Ki-67 ≤13.25% were entered into the trial and were treated without radiotherapy (n = 500)⁹.

Over five years, ten women had a recurrence, equating to a cumulative risk of 2.3%. There were eight cases of contralateral breast cancer, giving a cumulative five-year risk of 1.9%. The risk of any recurrence was 2.7%⁹.

Disease-free survival (DFS) was 89.9% at five years, and overall survival (OS) was 97.2%, similar to that seen in patients treated with radiotherapy, Dr Whelan pointed out.

The report shows that women aged 55 years and older with T1N0 grade 1-2 luminal A breast cancer treated with endocrine therapy alone following breast-conserving surgery have a very low recurrence rate⁹.

The prospective and controlled nature of the trial suggests these patients are candidates for the omission of radiotherapy, he added.

Maintenance treatment for ovarian cancer

Elsewhere, Dr Bradley Monk from the GOG Foundation and the University of Arizona presented the latest data from the ATHENA-MONO trial¹⁰ of rucaparib monotherapy as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. The trial population was newly diagnosed stage III-IV high grade epithelial ovarian, fallopian tube or primary peritoneal cancer, recruited at two hundred centres in twenty-four countries.

The data presented at the conference were accrued over a median follow-up of 26 months, with a cut-off date of 23 March 2022. Participants initiated rucaparib at a dose of 600 mg bid orally¹⁰.

In the homologous recombination deficiency (HRD) population, patients who received rucaparib monotherapy had a median PFS of 28.7 months compared to 11.3 months for patients receiving placebo, giving a hazard ratio of 0.47¹⁰. In the intention-to-treat (ITT) population, rucaparib monotherapy was associated with a median PFS of 20.2 months compared to 9.2 months for those who received a placebo, translating to a hazard ratio of 0.52¹⁰. 

Dr Monk said the results demonstrate that rucaparib delivers benefits regardless of BRCA mutation and HDR status. 

More than 58% of patients treated with rucaparib who had HRD molecular signatures had a response, with a long duration of 16.7 months¹⁰. Almost 49% of the ITT population responded, with a median duration of response of more than 22 months¹⁰. About 10% of patients had persistent disease. These patients continued to respond to treatment in the HRD and ITT populations.

The proportion of patients reporting at least one adverse event (AE) of any grade was similar in both groups; however, 60.5% of patients receiving rucaparib experienced a grade ≥3 AE compared to 22.7% in the placebo arm¹⁰.

Significantly, more than 70% of patients continued to receive rucaparib at a dose of at least 500 mg bid through 12 months¹⁰.

Novel treatment for hormone-sensitive prostate cancer

In one of the day’s virtual presentations, Dr Ding-Wei Ye from Fudan University Shanghai Cancer Center presented the findings of the phase 3 CHART trial¹¹ of the novel androgen receptor inhibitor SHR3680 in combination with androgen deprivation therapy (ADT) versus bicalutamide and ADT for patients with high volume metastatic hormone-sensitive prostate cancer (mHSPC).

654 patients were randomised to receive ADT and either 240 mg/d SHR3680 (n = 326) or 50 mg/d bicalutamide (n = 328). At the data cut off, the average follow up duration for SHR3680 was 22.1 months and 20.4 months for bicalutamide. The data presented in this study demonstrated that SHR3680 significantly reduced the risk of rPFS or death with a HR of 0.44. Additionally, the overall survival observed in SHR3680 compared to bicalutamide group increased to HR 0.58. The study also showed that grade ≥3 treatment-related adverse events were reported in 19.2% and 13.9% of patients in SHR3680 and bicalutamide, respectively¹¹.

Due to these results, Dr Ye reported that SHR3680 has now been submitted for regulatory approval¹¹.

The relationship between event-free survival and residual cancer burden

As ASCO 2022 ended, there were still many presentations on the last day, with dedicated sessions on molecular-based treatment for endometrial cancer, the management of myeloproliferative neoplasms in the molecular era, and controversies in adjuvant therapy for advanced endometrial cancer.

In one of the last sessions of the conference, Dr Lajos Pusztai from Yale Cancer Center reported the findings of an exploratory analysis of the KEYNOTE-522 trial¹². The analysis sought to determine if the event-free survival (EFS) response to neoadjuvant and adjuvant pembrolizumab was influenced by residual cancer burden (RCB). RCB categories ranged from 0 to 3, increasing with increasing disease burden.

Dr Pusztai and colleagues found that an increased RCB score was associated with worse EFS. Pembrolizumab plus chemotherapy prolonged EFS compared to chemo alone in the RCB 0, 1, and 2 categories. Patients with the residual disease had lower RCB values in the pembrolizumab arm, including fewer patients with RCB-3¹². 

Dr Pusztai pointed out that the subset of patients in the RCB 3 category had a poor prognosis, and he said new treatments are needed to improve outcomes for these patients.

Authors note: Day 5 was a half-day event

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.