AACR 2018: first-line atezolizumab, bevacizumab plus chemotherapy active in non-squamous NSCLC – Medical Writer Agency | 醫學作家香港 | 醫學寫作 | MediPR

Non-Sponsored Content

IMMUNO-THERAPY

AACR 2018: ADDITION OF ATEZOLIZUMAB TO BEVACIZUMAB AND CHEMOTHERAPY IMPROVES PROGRESSION-FREE SURVIVAL IN NON-SQUAMOUS LUNG CANCER

Medical writer: Stijn van den Borne, MSc | Last updated: 10th May 2018 | In: Chemotherapy, ImmunoOncology, Immunotherapy, Lung Cancer, Oncology, Translational Research

Article Keywords

AACR 2018, atezolizumab, carboplatin, chemotherapy, Genentech, Immunotherapy, non-squamous cell lung cancer, NSCLC, Oncology News, paclitaxel, PD-L1, Roche

Patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with first-line atezolizumab (Tecentriq®) plus bevacizumab (Avastin®), carboplatin, and paclitaxel had a 38% reduction of risk for progression disease or death compared with patients treated with bevacizumab and chemotherapy alone. The emerging data of the IMpower150 (NCT02366143) study were presented at the ELCC 2018 and the AACR 2018 conferences.

The IMpower150 study showed that addition of the anti-programmed death 1 ligand (PD-L1) antibody to bevacizumab and platinum-based chemotherapy resulted in a median progression-free survival (PFS) of 8.3 months. Patients treated with bevacizumab plus carboplatin and paclitaxel had a median PFS of 6.8 months (hazard ratio [HR]=0.62; 95% CI, 0.52-0.74; P<0.0001). See the interactive Forest plot (Figure 4) for all results.

“The trial [IMpower150] explored these combinations because atezolizumab’s T-cell mediated cancer cell killing may be enhanced through bevacizumab’s reversal of VEGF-mediated immunosuppression, while the chemotherapy of carboplatin plus paclitaxel may induce immune responses,”

Prof. Martin Reck of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Germany presented the IMpower150 results during the ELCC 2018.

The Phase III IMpower150 randomised 1202 stage IV non-squamous NSCLC patients 1:1:1 to receive atezolizumab plus carboplatin and paclitaxel (ARM A), atezolizumab plus bevacizumab, carboplatin and paclitaxel (ARM B), or bevacizumab plus carboplatin and paclitaxel (ARM C) (Figure 1).

The co-primary endpoints were investigator-assessed PFS in the intention-to-treat (ITT) EGFR wild-type (wt) population, investigator-assessed PFS in the T-effector (T_eff) gene signature high population, and overall survival (OS) in the ITT-wt population.

Roche, the manufacturer of both atezolizumab and bevacizumab, issued a press release in March 2018 stating the OS co-primary endpoint to be positive. The OS results are pending presentation at an upcoming meeting.

Figure 1. IMpower150 (NCT02366143) clinical study design. Presented data during the ELCC and AACR 2018 focussed solely on ARM B and ARM C.

IMPower150 Reck Kowanetz Socinski ELCC AACR 2018 firstline atezolizumab bevacizumab chemotherapy non-squamous nsclc design

MediPaper Medical Communications Ltd.

Newsletter Sign-Up

Do you like our content? Subscribe to our non-intrusive newsletter today! We promise we won’t be spammy.

ASCO 2021 Liver Cancer Update

Advancing care for advanced renal cell carcinoma: choosing the optimal therapy for you patients

the-evolving-role-of-nk1-in-cinv-management-chemotherapy-induced-nausea-vomiting-akynzeo-nepa-palonosetron-netupitant

The evolving role of NK₁ in CINV management

Lung Cancer Update April 2021

11th June 2021

ASCO 2021 Liver Cancer Update

19th April 2021

Advancing care for advanced renal cell carcinoma: choosing the optimal therapy for you patients

All patients received carboplatin (area under the concentration-time curve [AUC] 6) and paclitaxel (200 mg/m²) on day 1 of every 3 weeks (q3w) for 4 or 6 cycles. Atezolizumab was administered intravenously (IV) at 1200 mg q3w, and IV bevacizumab was given at 15 mg/kg q3w. Maintenance therapy for patients in ARM A was atezolizumab alone, in ARM B bevacizumab plus atezolizumab, and in ARM C bevacizumab alone.

At interim analysis, which was designed to compare arms B and C of the IMpower150, the median follow-up was approximately 15 months. The results in the ITT population are displayed in Table 1 and Figure 2.

**Table 1.** The median PFS, 6- and 12-month PFS rates, and response rates of the ITT population in ARM B (atezolizumab plus bevacizumab, carboplatin and paclitaxel) and ARM C (bevacizumab plus carboplatin and paclitaxel) of the IMpower150 study. DOR: duration of response; ITT: intention-to-treat; PFS: progression-free survival.
	Median PFS	6-mo PFS	12-mo PFS	ORR	CR	PR	median DOR
ARM B	8.3 mo	67%	56%	64%	4%	60%	9.0 mo
ARM C	6.8 mo	37%	18%	48%	1%	47%	5.7 mo

Figure 2. Comparison of the response rates between atezolizumab (ATEZO) plus bevacizumab (BEV), carboplatin and paclitaxel (CP) vs bevacizumab (BEV) plus carboplatin and paclitaxel (CP) in the IMpower150 study. CR: complete response; PD: progression disease; PR: partial response; SD: stable disease.

[chart id=”29″]

PD-L1+ ≥50% of TC or ≥10% of IC;
pd-l1 low: TC1/2 or IC 1/2 = ≥1% PD-L1+ TC <50% or ≥1% PD-L1+ IC <10%
PD-L1 negative: TC0 and IC0 = PD-L1+ <1% of TC and IC

Translational Research

The IMpower150 looked at translational components, such as the T_eff gene signature and PD-L1 expression by immunohistochemistry (IHC) with both the SP142 and SP263 assays. The T_eff gene signature is defined by mRNA expression of 3 genes, including PD-L1, CXCL9, and IFNγ. It is a surrogate for both PD-L1 expression and pre-existing immunity.

“In the OAK study, the T_eff gene signature appeared to be a more sensitive biomarker of PFS benefit for monotherapy atezolizumab versus docetaxel than PD-L1 IHC expression.”

~Mark A. Scozinski, MD of the Florida Hospital Cancer Institute in the United States presented the IMpower150 results during the AACR 2018.

Figure 3. Comparison of the response rates between atezolizumab (ATEZO) plus bevacizumab (BEV), carboplatin and paclitaxel (CP) vs bevacizumab (BEV) plus carboplatin and paclitaxel (CP) in the T_eff-high EGFR-wt subpopulation of the IMpower150 study. CR: complete response; PD: progression disease; PR: partial response; SD: stable disease.

[chart id=”30″]

**Table 2.** The median PFS, 6 and 12-month PFS rates, and response rates of the T_eff-high EGFR-wt population in ARM B (atezolizumab plus bevacizumab, carboplatin and paclitaxel) and ARM C (bevacizumab plus carboplatin and paclitaxel) of the IMpower150 study. DOR: duration of response; ITT: intention-to-treat; PFS: progression-free survival; wt: wild-type.
	Median PFS	6-mo PFS	12-mo PFS	ORR	CR	PR	median DOR
ARM B	11.3 mo	72%	57%	69%	5%	64%	11.2 mo
ARM C	6.8 mo	46%	18%	54%	2%	52%	5.7 mo

Median PFS in the T_eff-high cohort, a co-primary endpoint, was 11.3 months (95% CI, 9.1-13.0) when atezolizumab was added to bevacizumab plus the platinum-doublet, compared to 6.8 months (95% CI, 5.9-7.4) with bevacizumab and platinum-doublet chemotherapy alone (HR=0.51; 95% CI, 0.38- 0.68; P<0.0001). The 6-month and 12-month PFS-rates for the T_eff-high subgroup are displayed in Table 2. Additionally, Figure 3 shows the response rates in T_eff-high patients with EGFR-wt status. Finally, Figure 4 shows PFS outcomes and odds ratio (Forest plot) for different subgroups in the study.

Figure 4. Forest plot for median PFS in different subgroups of the IMpower150 study. The study showed that the T_eff gene signature enriches for PFS similarly to PD-L1 IHC, including biomarker-negative patients.

IMPower150 Reck Kowanetz Socinski ELCC AACR 2018 firstline atezolizumab bevacizumab chemotherapy non-squamous nsclc

MediPaper Medical Communications Ltd.

Legend by Figure 4 and Table 3

ALK: anaplastic lymphoma kinase; ATEZO: atezolizumab; BEV: bevacizumab; CP: carboplatin + paclitaxel; EGFR: epidermal growth-factor receptor; IC: immune cells; IHC: immunohistochemistry; mo: months; ITT: intention-to-treat; PD-L1: programmed death ligand 1; PFS: progression-free survival; TC: tumour cells; wt: wild-type.

**Table 3.** Algorithm for PD-L1 staining by SP142, the companion diagnostic (CDx) IHC for atezolizumab
	PD-L1 level expression (TC/IC coding)	PD-L1 level expression (%)
PD-L1 high	TC3 or IC3	≥50% PD-L1+ TC or ≥10% PD-L1+ IC
PD-L1 low	TC1/2 or IC1/2	≥1%-49% PD-L1+ TC or ≥1%-9% PD-L1+ IC
PD-L1 negative	TC0 and IC0	PD-L1+ <1% of TC and IC

Safety

The incidence of any adverse events (AEs), including serious AEs and immune-related AEs (irAEs), was similar between treatment arms. Moreover, the occurrence of treatment-related serious AEs (SAEs) was comparable; addition of atezolizumab to bevacizumab plus chemotherapy in ARM B was associated with 25% treatment-related SAEs vs 19% for bevacizumab plus chemotherapy in ARM C.

Roche noted that no new safety signals were identified when adding atezolizumab to the bevacizumab/chemotherapy combination and that the safety of the PD-L1 inhibitor combination appeared consistent with the known safety profile of the individual drugs.

Common atezolizumab-related side effects.

References

Reck M, et al. ESMO IO 2017 [LBA_PR1]

Reck M, et al. Ann Oncol 2017;28(11)

Reck M, et al. ELCC 2018 [134PD]

Kowanetz M & Socinski M, et al. AACR 2018 [CT076]

Roche. IMpower150 Media Release (2018, March 26). [Press release]

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).

Second-line treatment of gastric cancer or cancer of the gastroesophegeal junction: a case study of ramucirumab in Hong Kong

Capivasertib added to fulvestrant improves progression-free survival in advanced breast cancer patients

Calaspargase pegol-mknl (Asparlas®) FDA approved in paediatric and young adult acute lymphoblastic leukaemia (ALL) patients

Fully resorbable synthetic matrix offers improved safety for breast cancer patients undergoing immediate breast reconstruction

Pembrolizumab FDA approved in hepatocellular carcinoma patients pretreated with sorafenib

Lorlatinib FDA approved for metastatic ALK-positive NSCLC

ESMO 2018 HCC ESMO18 Liver Cancer ESMO2018 hepatocellular carcinoma hepatobiliary cholangiocarcinoma BTC

ESMO 2018 HCC: The ESMO18 hepatobiliary cancer track summarised

Pembrolizumab plus chemotherapy approved for metastatic squamous NSCLC

Dr Joanne Chiu HKU management irAE hepatitis manage immune-mediated hepatitis immunotherapy I-O immunooncology immune-induced hepatitis

Management of Immune-Mediated Hepatitis: a Case Report

PARPi talazoparib FDA approved for deleterious gBRCAm HER2‑negative breast cancer

Anti-PD1 sintilimab plus biosimilar bevacizumab receive IND-status by China NMPA

IMpower133: first-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer

Pembrolizumab plus chemotherapy effective in squamous NSCLC

Ipilimumab plus nivolumab for persistent or recurrent ovarian cancer

Brigatinib prolongs PFS compared to crizotinib in ALK-Positive NSCLC

CAR-T axicabtagene ciloleucel granted Orphan Drug designation for B-Cell Lymphoma by the Japan MHLW

PD-1 mAB cemiplimab FDA approved for locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC)

JAVELIN Lung 200 avelumab vs docetaxel in patients with pretreated advanced non-small cell lung cancer NSCLC

JAVELIN Lung 200: avelumab vs docetaxel for pretreated NSCLC

Dacomitinib FDA approved for the first-line treatment of metastatic EGFR-mutated NSCLC

©United States Food and Drug Agency US FDA

Duvelisib FDA approved for adult patients with R/R CLL or SLL

©United States Food and Drug Agency US FDA

Duvelisib FDA approved for adult patients with R/R follicular lymphoma

Frontline atezolizumab plus chemotherapy improves PFS in NSCLC

First-line osimertinib vs EGFR-TKI in Asian patients with advanced NSCLC

Early breast cancer treatment in China remains conservative

immuno-oncology I-O treatment for the irAE Rash

©MediPaper Medical Communications Ltd

ImmunoOncology: Dr Oscar Chan on the treatment of irAE rash

Prof Stefan Kasper on I-O in EXTREME-ineligible Head and Neck Cancer I-O in SCCHN with focus on EXTREME-ineligible Patients and the future directions of combination immunotherapy

Prof Stefan Kasper on I-O in EXTREME-ineligible SCCHN

Venetoclax FDA label updated to include Minimal Residual Disease negativity data

Quizartinib receives Orphan Drug designation for FLT3-mutated AML in Japan

Capmatinib plus gefitinib promising in MET-dysregulated NSCLC

CAR-TCR Summit 2018: Preliminary first-in-human data with CAR-Claudin18.2-T in gastric and pancreatic cancer

DRIVER connects cancer patients in China and the United States to the best care

Blood-based TMB-assay predicts response to atezolizumab in NSCLC patients

Plasma TMB predicts response to atezolizumab in NSCLC patients

First-in-Class Oncology Vaccine BIL06v Starts Phase 1 Evaluation

Nivolumab FDA approved for patients with metastatic small cell lung cancer (SCLC)

Pembrolizumab and atezolizumab USPIs updated by FDA

Nivolumab FDA approved for patients with metastatic small cell lung cancer (SCLC)

Pembrolizumab plus pemetrexed-platinum approved for use in the 1st-line treatment of metastatic non-squamous NSCLC

Pembrolizumab plus pemetrexed-platinum FDA approved for first-line treatment of metastatic non-squamous NSCLC

Talazoparib in advanced breast cancer patients with a germline BRCA1/2 mutation

CheckMate 032 Nivolumab ipilimumab metastatic esophagogastric cancer

CheckMate 032: Nivolumab +/- ipilimumab for metastatic esophagogastric cancer

Lenvatinib FDA approved for 1st-line treatment of HCC

©Alex011973 / 123RF Stock Photo

Pan-EGFR TKI pirotinib has commenced into Phase II clinical testing in China

FDA approved lusutrombopag (Mulpleta, Shionogi Inc.) for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. More Information. July 31, 2018.

FDA approved mogamulizumab for adult patients with relapsed or refractory CTCL

Lusutrombopag FDA approved for thrombocytopenia in adult chronic liver disease patients

Ribociclib FDA label updated to include pre- and perimenopausal women

Iobenguane I-131 FDA approved for rare adrenal neuroendocrine tumours

T790M osimertinib nsclc brain metastasis CNS metastases Osimertinib in patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer and brain metastases AURA3

Osimertinib in patients with T790M-positive advanced non-small cell lung cancer and brain metastases (AURA3)

Anti-PD1 with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma

Ivosidenib FDA approved for relapsed or refractory acute myeloid leukemia

FDA approved enzalutamide (XTANDI, Astellas Pharma US, Inc.), for patients with castration-resistant prostate cancer (CRPC). More Information. July 13, 2018

Filgrastim-aafi FDA approved as Filgrastim Biosimilar

Ribociclib FDA label updated to include pre- and perimenopausal women

Enzalutamide FDA approved for castration-resistant prostate cancer (CRPC)

EBV pembrolizumab gastric cancer - MSI-H pembrolizumab gastric cancer - CPS pembrolizumab gastric cancer - MSI, EBV, CPS predict pembrolizumab outcome in gastric cancer

EBV, MSI, and CPS predict pembrolizumab outcome in gastric cancer

Ipilimumab plus nivolumab FDA approved for MSI-H and dMMR pre-treated mCRC

Combination encorafenib plus binimetinib for unresectable/metastatic BRAF V600E or V600K-positive melanoma FDA approved

ASCO 2018 nsclc immunotherapy ASCO18 lung cancer pembrolizumab avelumab nivolumab duravalumab ipilimumab osimertinib dacomitinib lorlatinib crizotinib alectinib keytruda KEYNOTE CheckMate JAVELIN IMpower

ASCO 2018 NSCLC: The ASCO18 Lung Cancer Track Summarised

FDA has limited the use of Tecentriq and Keytruda for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing therapy. More Information. June 19, 2018

FDA limits use of atezolizumab and pembrolizumab in urothelial carcinoma

ASCO 2018 breast cancer TNBC MBC ABC ASCO18 PHEREXA D-CARE ABCSG-18 ASTRRA TEXT SOFT MONARCH-2 MONALEESA-3 SANDPIPER BOLERO-6 TOPACIO KEYNOTE-162 TONIC TOPACIO GeparNeuvo

ASCO 2018 Breast Cancer: The ASCO18 breast cancer track summarised

Bevacizumab in combination with carboplatin and paclitaxel FDA approved for several types of gynaecological cancers

FDA approved pembrolizumab for 3rd-line PMBCL in adult and pediatric patients

FDA approved pembrolizumab for chemotherapy-refractory r/m cervical cancer with PD-L1 CPS ≥1

ASCO18 ASCO 2018 HCC hepatocellular carcinoma liver cancer pembrolizumab KEYTRUDA atezolizumab TECENTRIQ PD-1 PD-L1 immunecheckpoint immunotherapy ramucirumab cabozantinib KEYNOTE-224 SCRUM-Japan GI-SCREEN CELESTIAL REACH-2

ASCO 2018 HCC: The ASCO18 hepatocellular cancer track summarised

FDA approves venetoclax in 2nd-line for patients with CLL or SLL

FDA approved biosimilar pegfilgrastim to decrease the chance of febrile neutropenia in patients with non-myeloid cancers on myelosuppressive chemotherapy

US FDA approved CAR-t cell BiTE DAR-T cell CD19 Immunotherapies blinatumomab axicabtagene ciloleucel tisagenlecleucel

FDA approved osimertinib for the 1st-line treatment of patients with EGFR exon 19 deletions or exon 21 L858R mutations positive metastatic non-small cell lung cancer (NSCLC)

NCT02578680 Keynote189 AACR 2018 pembrolizumab chemotherapy nsclc NEJM Leena Gandhi

krishnacreations / 123RF Stock Photo

FDA granted accelerated approval to blinatumomab for the treatment of adult and paediatric patients with B-cell precursor ALL in first or second complete remission with MRD ≥0.1%

Making sense of 1st-line immunotherapy in non-small cell lung cancer (NSCLC)

manuela schmidinger sutent sunitinib ae management manuela schmidinger manuela schmidinger sutent sunitinib side-effect management sutent sunitinib toxicity management Sutent Sunitinib AE management toxicity management side-effect management sorafenib pazopanib axitinib regorafenib vandetanib cabozantinib lenvatinib bevacizumab VEGFR VEGF renal cell carcinoma RCC kidney cancer renal cell cancer schmidinger

Achieving Long-Term Survival in the First-Line Treatment of Metastatic Renal Cell Carcinoma; A Balancing Act of Efficacy and Side-Effects

2016 pancreatic cancer awareness month IMM-101 plus Gemcitabine medipaper medical communications medical writer hire healthcare writers hong kong

Trackbacks & Pingbacks

First-line atezolizumab, bevacizumab plus chemotherapy active in non-squamous NSCLC | ['mediPr] says:

10th April 2020 at 9:36 PM

[…] Source link […]

Log in to Reply
ASCO 2018 NSCLC: The ASCO18 Lung Cancer Track Summarised says:

25th June 2018 at 10:37 PM

[…] therapies were presented, including CheckMate 227 with nivolumab (NIVO), IMpower131 and IMpower150 studies with atezolizumab (ATEZO), and KEYNOTE-042 and KEYNOTE-407 studies with pembrolizumab […]

Log in to Reply
Approved Immune-Checkpoint Inhibitors and Immunotherapies per 23-APR-2018 says:

13th June 2018 at 11:01 PM

[…] /wp-content/uploads/2018/05/1527523293_Oncology-Breast-CNS-Chemotherapy-Endocrine-GI-GU-Geriatric-Gynecologic-GYN-OB-Head-and-Neck-Haematology-Immunotherapy-Lung-Melanoma-Skin-NET-Paediatric-Pathology-Sarcoma-Surgery-Targeted-Therapy-Translational-05.jpg 338 450 Stijn van den Borne, MSc /wp-content/uploads/2018/04/MediPR-MediPaper-Medical-Communications-Ltd-Healthcare-Writers-Medical-Writers-Medical-Writer-Agency-Hong-Kong-Medical-Writing-Services-Solutions-Quote-醫學寫作-香港-醫學作家香港-medical-PR-medical-public-relations-e1523021883812.png Stijn van den Borne, MSc2018-05-18 10:39:232018-06-04 09:45:37FDA safety alert: use of immunotherapy in metastatic urothelial cancer with low PD-L1 expressionbravajulia / 123RF Stock Photo […]

Log in to Reply
First-line atezolizumab, bevacizumab plus chemotherapy active in non-squamous NSCLC - MediNews Asia says:

24th May 2018 at 12:13 AM

Patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with first-line atezolizumab (Tecentriq®) plus bevacizumab (Avastin®), carboplatin, and paclitaxel had a 38% reduction of risk for progression disease or death compared with patients treated with bevacizumab and chemotherapy alone. The emerging data of the IMpower150 (NCT02366143) study were presented at the ELCC 2018 and the AACR 2018 conferences.

Log in to Reply

Want to join the discussion?
Feel free to contribute!