MATCH: Low-Dose Radiotherapy, Atezolizumab, and Chemo in ES-SCLC

In the single-arm, phase 2 MATCH study ( Identifier: NCT04622228), the combination of low-dose radiotherapy, atezolizumab, and chemotherapy demonstrated antitumor activity in patients with ES-SCLC.2

The study included 56 treatment-naïve adults with ES-SCLC from 8 centers in China. The patients had an ECOG performance status of 0 or 1, their median age was 58.9 years, and 87.5% were men. 

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The treatment regimen consisted of atezolizumab (1200 mg on day 1), cisplatin (75 mg/m2 on day 1) or carboplatin (AUC, 5 on day 1), and etoposide (100 mg/m2 on days 1-3) for 4 cycles (21 days each). Low-dose radiotherapy (15 Gy in 5 fractions) was given on days 1-5 of the first cycle. Patients also received atezolizumab maintenance until loss of clinical benefit or unacceptable toxicity occurred. 

The median follow-up was 14.8 months. The objective response rate (ORR) was 87.5%. All responses were partial responses. The disease control rate was 94.6%. 

The median progression-free survival (PFS) was 6.9 months. The PFS rate was 56.5% at 6 months and 27.7% at 12 months. The median overall survival (OS) was not reached. The 12-month OS rate was 71.9%. A total of 19 patients died.

The most common grade 3-4 AEs were reductions in neutrophil counts (60.7%), white blood cell counts (58.9%), and platelet counts (23.2%). One patient had fatal AEs (pneumonia and pulmonary embolism). 

Amy Cummings, MD
Amy Cummings, MD

Four patients discontinued treatment due to AEs. Immune-related AEs occurred in 37.5% of patients. The most common were hyperthyroidism (5.4%) and rash (5.4%). 

These findings suggest that low-dose radiotherapy provides an OS benefit with no added toxicity, according to Amy Cummings, MD, of UCLA Health in Santa Monica, California, who was not involved in this study.  

“While a primary outcome of ORR in a trial that incorporates radiation to known sites of disease is a lower bar, this could be overcome by correlative studies suggesting inflammatory enrichment and a greater proportion of participants with durable response,” Dr Cummings said. “While not enough to change practice on its own, it is a space to watch, and I will be excited to see how these survival curves mature.”

Rucaparib and Nivolumab Maintenance in Platinum-Sensitive ES-SCLC 

Maintenance therapy with rucaparib and nivolumab showed “promising activity” when given after frontline chemotherapy to patients with platinum-sensitive ES-SCLC, according to researchers.3

In this single-arm, phase 2 trial ( Identifier: NCT03958045), patients with ES-SCLC completed 4-6 cycles of platinum doublet chemotherapy (cisplatin or carboplatin plus etoposide or irinotecan), with or without prophylactic cranial irradiation. 

There were 33 patients who had at least a partial response to chemotherapy and received maintenance with nivolumab at 480 mg every 4 weeks and rucaparib at 600 mg twice daily. 

The study’s primary endpoint was PFS. The median PFS was 3 months from the time of enrollment (post-chemotherapy) and 11 months from the first cycle of chemotherapy.

A majority of patients (89.8%) were alive at 12 months, and 54.4% of patients were alive at 24 months from the start of chemotherapy. Two patients are currently on active treatment, and 2 patients are on observation with stable disease after completing treatment. 

Grade 3-4 AEs included hypokalemia, hyponatremia, elevated alanine aminotransferase, neutropenia, and white blood cell decrease (n=1 for all). There were no grade 5 AEs. 

Tércia Reis, MD
Tércia Reis, MD

Despite all the limitations of a phase 2 study and the small number of patients evaluated, the maintenance rucaparib combined with ICI [immune checkpoint inhibitor] therapy was tolerable and demonstrated promising activity following frontline chemotherapy in platinum-sensitive ES-SCLC,” said Dr Reis, who was not involved in this study.  

“The use of PARP inhibition in SCLC has not demonstrated significant benefit to date,” said Karen Reckamp, MD, of Cedars-Sinai Medical Center in Los Angeles, who was not involved in this study. “Evaluation of PARP inhibition and immune checkpoint inhibition in the maintenance setting following initial chemoimmunotherapy has developed from preclinical investigations demonstrating potential augmentation of response.” 

Dr Reckamp said maintenance rucaparib and nivolumab should be evaluated in a larger trial, and “patient selection should be considered, as emerging data on SCLC subsets suggests varied responses to immunotherapy that may alter outcomes.”