ASCO 2020 Lung, Breast, and Liver Cancer Update

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ASCO 2020 VIRTUAL MEETING

SPOTLIGHT ON LUNG, BREAST AND HEPATOCELLULAR CANCER

By: Kirsty LEE | Last updated: 30th June 2020 | In: ASCO 2020 Annual Meeting, Breast Cancer, Chemotherapy, China, Conferences, Endocrine Therapy, Gastrointestinal Cancer, ImmunoOncology, Immunotherapy, Lung Cancer, Oncology, Targeted Therapies

This year, ASCO 2020 was held as a virtual conference due to the COVID-19 pandemic. This is a summary of key trials presented at ASCO, focusing primarily on breast cancer, liver cancer, and lung cancer.

However, one major result not in these three categories presented at ASCO 2020 were the final results of the KEYNOTE-177 study investigating pembrolizumab (Keytruda®) versus chemotherapy for MSI-H/dMMR mCRC.¹

Pembrolizumab as first-line treatment doubled PFS (median 16.5 months vs. 8.2 months), a clinically meaningful and statistically significant improvement (HR=0.60; 95% CI: 0.45-0.80; P=0.0002). Fewer treatment-related AEs were also observed with pembrolizumab.¹

ASCO 2020 Keywords

ABC, AE, Alecensa, alectinib, ALK, apatinib, atezolizumab, Avastin, bevacizumab, capecitabine, carboplatin, CDK4/6, CDK46, cisplatin, CNS metastases, coronavirus, CPS, CRC, crizotinib, dMMR, donafenib, durvalumab, EGFR, ELM4-ALK, ES-SCLC, etoposide, gBRCAm, gPALB2m, HER2-negative, HER2-positive, Herceptin, HR-positive, Imfinzi, Keytruda, Lynparza, MBC, mCRC, mesothelioma, MPM, MSI, MSI-H, Nexavar, nivolumab, NSCLC, olaparib, Opdivo, osimertinib, PARP, PARPi, PD-1, PD-L1, pembrolizumab, sBRCAm, SCLC, sorafenib, Tagrisso, talazoparib, Talzenna, Tecentriq, TNBC, trastuzumab, tucatinib, Xalkori, Xeloda

A number of breast cancer trials were of note at ASCO 2020

Results of KEYNOTE-355 were presented, and pembrolizumab (Keytruda®) in combination with chemotherapy showed clinically meaningful improvement in PFS vs. chemotherapy alone (mPFS 9.7 vs 5.6 mo; HR=0.65; 95% CI: 0.49-0.86; P=0.0012) in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumours expressed PD-L1 (CPS ≥10).²

A meta-analysis of CDK4/6 inhibitors confirmed the PFS benefit of CDK4/6i plus ET in HR+/HER2- MBC (pooled HR=0.55; 95% CI: 0.50-0.59; P<0.00001) and demonstrated an OS benefit when all RCTs of all 3 CDK4/6i were included (pooled HR=0.75; 95% CI: 0.68-0.84; P<0.00001).[mfn referencenumber=3]Kunwor R, et al. J Clin Oncol 38: 2020 (suppl; abstr 1060).[/mfn]

Two PARP inhibitors also displayed promising results – olaparib (Lynparza®) displayed activity in patients with MBC and sBRCA1/2 or gPALB2 mutations in a proof-of-principle study⁴, and talazoparib (Talzenna®) could be of clinical benefit to HER2 ABC patients who were selected based on their gBRCA mutational status.⁵

Lastly, in the HER2CLIMB trial, tucatinib in combination with trastuzumab (Herceptin®) and capecitabine was also shown to double the intracranial confirmed ORR (47.3% vs. 20.0%) in patients with heavily previously treated HER2+ MBC with brain metastases.⁶ This combination has the potential to become the new standard of care in patients with HER2+ MBC, with and without brain metastases.⁶

Positive results were reported in ES-SCLC, NSCLC and MPM lung cancers

Two trials reported positive results for first-line treatment of ES-SCLC.
Durvalumab (Imfinzi®) + EP also demonstrated improvement in OS vs. EP alone (HR=0.75; 95% CI: 0.62-0.91; nominal P=0.0032; median 12.9 vs. 10.5 mo), with consistent safety profiles.⁷

Pembrolizumab (Keytruda®) + EP significantly improved PFS in the ITT population vs placebo + EP (HR=0.75; 95% CI: 0.61-0.91; P=0.0023; median 4.5 vs. 4.3 mo), with no unexpected toxicities observed.⁸

Another PD-1 inhibitor, nivolumab (Opdivo®), reported an mPFS of 4.1 months and mOS of 13.3 months in a retrospective real-world study of MPM patients in Japan, suggesting it could be used as a standard second-line treatment for MPM.⁹

In NSCLC patients, 5-year OS and updated safety data was reported from the ALEX study, investigating alectinib (Alecensa®) vs. crizotinib (Xalkori®) in untreated advanced ALK+ NSCLC. 5-year survival rate was 62.5% with alectinib vs. 45.5% with crizotinib, and in patients with and without CNS mets at baseline, the OS HR was 0.58 (95% CI: 0.34-1.00) and 0.76 (95% CI: 0.45-1.26), respectively.¹⁰

With EGFR+ NSCLC, osimertinib (Tagrisso®) as an adjuvant therapy after complete tumour resection showed a DFS HR of 0.17 (95% CI: 0.12-0.23; P<0.0001) in Stage II-IIIA patients. 2-year DFS rate was 90% with osimertinib vs. 44% with placebo, and the safety profile was consistent with the known safety profile of osimertinib.¹¹

A few trials on HCC also reported favourable results

In a phase II/III trial, donafenib as a first-line therapy was found to significantly improve OS over sorafenib in advanced HCC (mOS in full analysis set 12.1 vs. 10.3 mo; HR=0.831; 95% CI: 0.699-0.988; P=0.0363), with a favourable safety and tolerability profile.¹²

In second-line treatments, apatinib significantly prolonged OS (mOS 8.7 vs. 6.8 mo; HR=0.785; 95% CI: 0.617-0.998; P=0.0476) and PFS (mPFS 4.5 vs. 1.9 mo; HR=0.471; 95% CI: 0.369-0.601; P<0.0001) over placebo in Chinese patients with pretreated advanced HCC.[mfn referencenumber=13]Li Q, et al. J Clin Oncol 38; 2020 (suppl; abstr 4507).[/mfn]

A network meta-analysis of first-line treatments for unresectable HCC also found greater OS and PFS benefits with first-line atezolizumab (Tecentriq®) + bevacizumab (Avastin®) compared to other treatments approved for this indication.¹⁴

Abbreviations

ABC=advanced breast cancer

AE=adverse event

ALK=anaplastic lymphoma kinase

ASCO=American Society of Clinical Oncology

CDK4/6i=cyclin-dependent kinase 4/6 inhibitor

CI=confidence interval

CNS=central nervous system

CPS=combined positive score

DFS=disease-free survival

dMMR=mismatch repair deficient

EGFR=epidermal growth factor receptor

ES-SCLC=extensive-stage small cell lung cancer

EP=etoposide plus platinum

ET=endocrine therapy

HCC=hepatocellular carcinoma

HER2=human epidermal growth factor receptor 2

HR=hazard ratio

HR+=hormone receptor positive

ITT=intention-to-treat

MBC=metastatic breast cancer

mCRC=metastatic colorectal cancer

mOS=median overall survival

mPFS=median progression-free survival

MPM=malignant pleural mesothelioma

MSI-H=microsatellite instability-high

NSCLC=non-small cell lung cancer

ORR=overall response rate

OS=overall survival

PARP=poly (ADP-ribose) polymerase

PD-1=programmed cell death protein 1

PD-L1=programmed death ligand 1

PFS=progression-free survival

RCT=randomized controlled trial

TNBC=triple negative breast cancer

References

Andre T, et al. J Clin Oncol 38: 2020 (suppl; abstr LBA4).

Cortes J, et al. J Clin Oncol 38: 2020 (suppl; abstr 1000).

Kunwor R, et al. J Clin Oncol 38: 2020 (suppl; abstr 1060).

Tung NM, et al. J Clin Oncol 38: 2020 (suppl; abstr 1002).

Litton JK, et al. J Clin Oncol 38: 2020 (suppl; abstr 1018).

Lin NU, et al. J Clin Oncol 38: 2020 (suppl; abstr 1005).

Paz-Ares LG, et al. J Clin Oncol 38: 2020 (suppl; abstr 9002).

Rudin CM, et al. J Clin Oncol 38: 2020 (suppl; abstr 9001).

Mikami K, et al. J Clin Oncol 38: 2020 (suppl; abstr 9052).

Peters S, et al. J Clin Oncol 38: 2020 (suppl; abstr 9518).

Herbst RS, et al. J Clin Oncol 38: 2020 (suppl; abstr LBA5).

Bi F, et al. J Clin Oncol 38; 2020 (suppl; abstr 4506).

Li Q, et al. J Clin Oncol 38; 2020 (suppl; abstr 4507).

Vogel A, et al. J Clin Oncol 38; 2020 (suppl; abstr 4585).

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).