Lung Cancer Update April 2021

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LUNG CANCER

Medical writer: Kirsty LEE | Last updated: 8 April 2021 | In: Lung Cancer, Oncology, Chemotherapy, Immunotherapy, Radiology, irAE Management, Targeted Therapies

Article Keywords

durvalumab, pleural effusion, osimertinib, chemotherapy, TAK-788, tremelimumab, QL1101, neoadjuvant, ES-SCLC, bevacizumab, REGN 2810, talazoparib, chemoradiotherapy, mesothelioma, dacomitinib, EGFR T790M, topotecan, SCLC, PD-L1, lung cancer, brigatinib, cemiplimab, malignant pleural mesothelioma, irAE, camrelizumab, NSCLC, MEDI4736, AP32788, nivolumab, mobocertinib, radiotherapy, DLL3, atezolizumab, nimotuzumab, HRRD, ipilimumab, olmutinib, EGFR, rovalpituzumab tesirine

With the World Conference on Lung Cancer (WCLC) 2020 completed in January 2021, several new and clinical relevant phase 2 and phase 3 studies on lung cancer have been published. We summarised some key data for you.

Brigatinib in Japanese Patients with ALK-Positive NSCLC Previously Treated with Alectinib and Other Tyrosine Kinase Inhibitors: Outcomes of the Phase 2 J-ALTA Trial

Makoto Nishio et al.

The J-ALTA trial found brigatinib had an ORR of 34%, with a median DoR of 11.8 months, in an alectinib-refractory NSCLC population. The DCR was 79%, and median PFS was 7.3 months. The trial was a single-arm multicentre, open-label study in Japanese patients refractory to ALK TKI or ALK TKI-naïve. The primary endpoint was IRC-assessed confirmed ORR.

NCT03410108 PMID: 33248320 DOI: 10.1016/j.jtho.2020.11.004

Durvalumab, With or Without Tremelimumab, Plus Platinum-Etoposide Versus Platinum-Etoposide Alone in First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer (Caspian): Updated Results From a Randomised, Controlled, Open-Label, Phase 3 Trial

Jonathan W Goldman et al.

Updated results from CASPIAN found first-line durvalumab plus platinum-etoposide maintained improved OS vs platinum-etoposide (Median OS 12.9 months vs 10.5 months; HR=0.75; 95% CI: 0.62-0.91; p=0.0032). Durvalumab plus tremelimumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. The trial was an open-label, randomised, phase 3 trial investigating durvalumab plus tremelimumab plus platinum-etoposide or durvalumab plus platinum-etoposide in treatment-naïve patients with extensive-stage SCLC. The primary endpoints were OS for durvalumab plus platinum-etoposide vs platinum-etoposide, and OS for durvalumab plus tremelimumab plus platinum-etoposide vs platinum-etoposide for the ITT population.

NCT03043872 PMID: 33285097 DOI: 10.1016/s1470-2045(20)30539-8

Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced Non-Small Cell Lung Cancer: 2-YEAR Follow-Up From a Randomised, Open-Label, Phase 3 Study (Checkmate 078)

Shun Lu et al.

A two-year update of CheckMate 078 found nivolumab maintained a favourable safety profile and continued to show improved OS compared to docetaxel, with a median OS of 11.9 months vs 9.5 months (HR=0.75; 95% CI: 0.61-0.93). The trial investigated nivolumab in patients with advanced/metastatic NSCLC who had disease progression after platinum-doublet CTx.

NCT02613507 PMID: 33321441 DOI: 10.1016/j.lungcan.2020.11.013

Camrelizumab Plus Carboplatin and Pemetrexed Versus Chemotherapy Alone in Chemotherapy-Naive Patients With Advanced Non-Squamous Non-Small-Cell Lung Cancer (CameL): A Randomised, Open-Label, Multicentre, Phase 3 Trial

Caicun Zhou et al.

The CameL trial found camrelizumab significantly prolonged PFS compared to CTx alone (11.3 months vs 8.3 months; HR=0.60; 95% CI: 0.45-0.79; p=0.0001). The randomised, open-label, multicentre phase 3 trial investigated camrelizumab plus CTx in 419 patients with non-squamous NSCLC without EGFR and ALK alterations, with a primary endpoint of PFS in all patients, and in patients who were PD-L1 positive.

NCT03134872 PMID: 33347829 DOI: 10.1016/s2213-2600(20)30365-9

Olmutinib in T790M-POSITIVE Non-Small Cell Lung Cancer After Failure of First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy: A Global, Phase 2 Study

Keunchil Park et al.

A phase 2 trial found 46.3% of patients receiving olmutinib had a confirmed objective response, with a best overall response of 51.9%. Confirmed DCR for al patients was 86.4%, and median objective DoR was 12.7 months. The trial assessed efficacy and safety of olmutinib in 162 patients with locally advanced or metastatic NSCLC with a T790M mutation, and disease progression on previous EGFR TKI therapy.

NCT02485652 PMID: 33434335 DOI: 10.1002/cncr.33385

IMPOWER132: Atezolizumab Plus Platinum-Based Chemotherapy vs Chemotherapy for Advanced NSCLC in Japanese Patients

Makoto Nishio et al.

The IMpower132 trial found atezolizumab plus pemetrexed and platinum-based CTx improved median OS compared with CTx alone (30.8 months vs 22.2 months; HR=0.63; 95% CI: 0.36-1.14) in the Japanese patient subgroup. Median PFS was 12.8 months vs 4.5 months, favouring the atezolizumab combination. The trial was an open-label, phase 3 trial evaluating atezolizumab plus pemetrexed and platinum-based CTx as first-line treatment for advanced NSCLC, with a dual primary endpoint of OS and PFS.

NCT02657434 PMID: 33462883 DOI: 10.1111/cas.14817

First-Line Nivolumab Plus Ipilimumab in Unresectable Malignant Pleural Mesothelioma (Checkmate 743): A Multicentre, Randomised, Open-Label, Phase 3 Trial

Paul Baas et al.

The CheckMate 743 trial found nivolumab plus ipilimumab significantly extended OS compared to CTx (18.1 months vs 14.1 months; HR=0.74; 96.6% CI: 0.60-0.91; p=0.0020). The open-label, randomised phase 3 trial enrolled 713 patients with previously untreated, histologically confirmed unresectable malignant pleural mesothelioma, with a primary endpoint of OS.

NCT02899299 PMID: 33485464 DOI: 10.1016/s0140-6736(20)32714-8

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer

Nobuyuki Yamamoto et al.

A phase 2 trial found the addition of nimotuzumab to concurrent chemoradiotherapy had an ORR of 69.2%, with a median PFS of 508 days and a treatment completion rate of 87.2%. The mulitcentre, single-arm, open-label phase 2 trial evaluated nimotuzumab with concurrent chemoradiotherapy in 40 patients with unresectable locally advanced NSCLC, with a primary endpoint of treatment completion rate.

JapicCTI-090825 PMID: 33518480 DOI: 10.1016/j.cllc.2020.12.012

Phase 2 Study of Bevacizumab Plus Carboplatin/Nab-Paclitaxel Followed by Bevacizumab Plus Nab-Paclitaxel for Non-Squamous Non-Small Cell Lung Cancer With Malignant Pleural Effusion

Motohiro Tamiya et al.

A phase 2 trial found the combination of bevacizumab plus carboplatin/paclitaxel led to an ORR of 58.3% and a DCR of 100%. Median PFS and OS were 14.4 months and 26.9 months, respectively. The trial evaluated the efficacy of this combination in CTx-naïve non-squamous NSCLC patients with malignant pleural effusion, with a primary endpoint of ORR.

UMIN000013329 PMID: 33544282 DOI: 10.1007/s10637-021-01076-8

Cemiplimab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With PD-L1 of at Least 50%: A Multicentre, Open-Label, Global, Phase 3, Randomised, Controlled Trial

Ahmet Sezer et al.

The EMPOWER-Lung 1 study found cemiplimab monotherapy significantly improved OS and PFS vs CTx (NR vs 14.2 months, and 8.2 months vs 5.7 months, respectively) in patients with advanced NSCLC with PD-L1 ≥50%. The trial was a multicentre, open-label, global phase 3 study with dual primary endpoints of OS and PFS. 710 patients were randomly assigned.

NCT03088540 PMID: 33581821 DOI: 10.1016/s0140-6736(21)00228-2

Phase 2 Study of Talazoparib in Patients With Homologous Recombination Repair-Deficient Squamous Cell Lung Cancer: Lung-Map Substudy S1400G

Taofeek K Owonikoko et al.

The Lung-MAP Substudy S1400G found talazoparib failed to show efficacy in patients with alterations in ATM, ATR, BRCA1, BRCA2, or PALB2, with an ORR of 4% and disease control rate of 54%. Median PFS and OS were 2.4 months and 5.2 months respectively. The trial was a signal finding study evaluating the efficacy of talazoarib in advanced stage squamous cell lung cancer with homologous recombination repair deficiency (HRRD).

NCT03377556 PMID: 33583720 DOI: 10.1016/j.cllc.2021.01.001

Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Operable Non-Small Cell Lung Cancer: the Phase 2 Randomised NEOSTAR Trial

Tina Cascone et al.

The NEOSTAR trial found that neoadjuvant nivolumab + ipilimumab had a higher complete response rate compared with nivolumab (38% vs 10%), but had similar rates of major pathologic response (24% vs 22%). The phase 2 trial investigated neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, with a primary endpoint of major pathologic response.

NCT03158129 PMID: 33603241 DOI: 10.1038/s41591-020-01224-2

Association of Immune-Related Adverse Events and Efficacy Outcomes With Consolidation Pembrolizumab After Chemoradiation in Patients With Inoperable Stage III Non-Small-Cell Lung Cancer

Nikhil Atul Shukla et al.

Retrospective analysis of a phase 2 trial found that ir AEs due to pembrolizumab were not associated with decreased efficacy outcomes. Patients who discontinued pembrolizumab early because of irAEs received significantly fewer cycles of pembrolizumab (5 vs 15; p=0.0016) without significant difference in PFS, OS, or time to metastatic disease or death. The trial was a retrospective analysis of a single-arm phase 2 trial evaluating consolidation pembrolizumab after chemoradiation in 92 patients with stage III NSCLC.

NCT02343952 PMID: 33610454 DOI: 10.1016/j.cllc.2020.12.014

Activity and Safety of Mobocertinib (TAK-788) In Previously Treated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations From a Phase 1/2 Trial

Gregory J Riely et al.

A phase 1/2 trial found that mobocertinib had a confirmed response rate of 43%, with a median DoR of 14 months and median PFS of 7.3 months, after dose escalation identified 160mg once daily as the recommended phase 2 dose. Mobocertinib is an oral EGFR inhibitor targeting the EGFR exon 20 insertion and was evaluated in patients with NSCLC.

NCT02716116 PMID: 33632775 DOI: 10.1158/2159-8290.cd-20-1598

Equivalent Efficacy Study of QL1101 and Bevacizumab on Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer Patients: A Phase 3 Randomised, Double-Blind Clinical Trial

Tingqing Chu et al.

A phase 3 trial found QL1101, a bevacizumab analogue, showed similar ORR to bevacizumab (52.8% and 56.8%, respectively). The trial aimed to test equivalence in efficacy and safety of QL1101 to bevacizumab, and enrolled 535 Chinese patients with untreated locally advanced non-squamous NSCLC in a 1:1 ratio. Primary endpoint was ORR.

PMID: 33710815

Safety and Efficacy of First-Line Dacomitinib in Asian Patients With EGFR Mutation-Positive Non-Small Cell Lung Cancer: Results From a Randomised, Open-Label, Phase 3 Trial (ARCHER 1050)

Ying Cheng et al.

The ARCHER 1050 trial found first-line dacomitinib significantly prolonged PFS compared with gefitinib (HR=0.509; 95% CI: 0.391-0.662; p<0.0001). The trial was a randomised, phase 3 trial in 346 patients with newly diagnosed EGFR mutation-positive NSCLC, with a primary endpoint of PFS. NCT01774721 PMID: 33721611 DOI: 10.1016/j.lungcan.2021.02.025

Patient-Reported Outcomes With Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC)

Edward B Garon et al.

Patient-reported outcomes from the MYSTIC trial found that durvalumab ± tremelimumab reduced symptom burden such as fatigue (nominal p<0.01) and improved time to deterioration compared to CTx. The trial was a phase 3 trial that did not meet its primary endpoints, but treatment-naïve patients with PD-L1 expression ≥25% were randomised 1:1:1 to receive durvalumab, durvalumab + tremelimumab, or CTx. NCT02453282 PMID: 33775558 DOI: 10.1016/j.cllc.2021.02.010

Effect of Second-Generation vs Third-Generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-YEAR Follow-up of a WJTOG0105 Phase 3 Randomised Clinical Trial

Yoshitaka Zenke et al.

The 10-year follow up of the WJTOG0105 trial found patients with weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60gy followed by 2 courses of paclitaxel/carboplatin consolidation had achieved similar 10-year survival probabilities as the control arm (15.2% vs 13.6%). The trial was a phase 3 randomised clinical trial in 440 patients with unresectable stage III NSCLC.

UMIN000030811 PMID: 33734289 DOI: 10.1001/jamaoncol.2021.0113

Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-HIGH SCLC: Results From the Phase 3 TAHOE Study

Fiona Blackhall et al.

TAHOE trial by Blackhall et al. found rovalpituzumab tesirine did not lead to a longer median OS when compared to topotecan (6.3 months vs 8.6 months; HR=1.46; 95% CI: 1.17-1.82). The trial was an open-label randomised phase 3 study of rovalpituzumab tesirine plus topotecan as second-line therapy in 444 patients with DLL3-high advanced or metastatic SCLC, with a primary endpoint of OS.

NCT03061812 PMID: 33607312 DOI: 10.1016/j.jtho.2021.02.009

First-Line Nivolumab Plus Ipilimumab Combined With Two Cycles of Chemotherapy in Patients With Non-Small-Cell Lung Cancer (Checkmate 9LA): An International, Randomised, Open-Label, Phase 3 Trial

Luis Paz-Ares et al.

CheckMate 9LA trial by Paz-Ares et al. found a significant improvement in OS with nivolumab plus ipilimumab vs CTx at pre-planned analysis (14.1 months vs 10.7 months; HR=0.69; 96.71% CI: 0.55-0.87; p=0.00065). The trial was a randomised, open-label phase 3 trial in 1150 patients with stage IV or recurrent NSCLC investigating the addition of two cycles of CTx to first-line nivolumab plus ipilimumab.

NCT03215706 PMID: 33476593 DOI: 10.1016/s1470-2045(20)30641-0

Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC – an Update From the PACIFIC Trial

Corrine Faivre-Finn et al.

An updated analysis of the PACIFIC trial by Faivre-Finn et al. found durable PFS with durvalumab, with 4-year PFS rates of 35.3% vs 19.5% with placebo (HR=0.55; 95% CI: 0.44-0.67), and sustained OS benefits. Median OS for durvalumab was 47.5 months compared to 29.1 months on placebo (HR=0.71; 95% CI: 0.57-0.88). The trial was a phase 3, placebo-controlled trial of consolidative durvalumab in 709 patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy.

NCT02125461 PMID: 33476803 DOI: 10.1016/j.jtho.2020.12.015

Efficacy of Osimertinib Plus Bevacizumab vs Osimertinib in Patients With EGFR T790M-Mutated Non-Small Cell Lung Cancer Previously Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor: West Japan Oncology Group 8715L Phase 2 Randomised Clinical Trial

Hiroaki Akamatsu et al.

The 8715L trial by Akamatsu et al found that osimertinib plus bevacizumab did not prolong PFS compared to osimertinib alone (9.4 months vs 13.5 months; adjusted HR=1.44; 80% CI: 1.00-2.08; p=0.20). However, ORR was improved (68% vs 54%). The trial enrolled patients with advanced lung adenocarcinoma with prior progression on EGFR-TKI treatment and acquired EGFR T790M mutation, with a primary endpoint of PFS.

UMIN000023761 PMID: 33410885 DOI: 10.1001/jamaoncol.2020.6758

Abbreviations:

AE, adverse event; ALK, anaplastic lymphoma kinase; CI, confidence interval; CTX, chemotherapy; DCR, disease control rate; DoR, duration of response; EGFR, epidermal growth factor receptor; HR, hazard ratio; irAE, immune-related adverse event; IRC, independent review committee; ITT, intention-to-treat; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; SCLC, small cell lung cancer; TKI, tyrosine kinase inhibitor; TRT, thoracic radiotherapy

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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).

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