The approval is based on P-III IMbrave150 study involves assessing of Tecentriq (1200mg) + Avastin (15 mg/kg) on day 1 of each 21-day cycle vs sorafenib (400mg, bid) on days 1-21 of each 21-day cycle in 501 patients in a ratio (2:1) with unresectable HCC, prior not treated with systemic therapies
Results: @median follow-up of 15.6mos., 34% reduction in OS; m-OS (19.2 vs 13.4mos.); mPFS (6.9 vs 4.3mos.). In Chinese population, m-OS (24.0 vs 11.4mos.)
Tecentriq + Avastin is an approved therapy across the globe, including in the US, China, Japan and the EU, for people with unresectable HCC and is recommended in many clinical practice guidelines globally
Click here to read full press release/ article | Ref: Roche | Image: BioSpace
Roche reports an exploratory analysis of P-III IMvigor010 study assessing efficacy and safety of adjuvant treatment with Tecentriq vs observation in 809 people with MIUC, who are at high risk of recurrence following resection
Results: in people with ctDNA, DFS Median (5.9 vs 4.4 mos.); median OS (25.8 vs 15.8 mos.). As presented in ASCO, the study did not meet its 1EPs of DFS (19.4 vs 16.6 mos.) in IIT population
In general, people with MIUC who had detectable ctDNA were more likely to benefit from treatment with adjuvant Tecentriq monothx. compared with those without ctDNA
Click here to read full press release/ article | Ref: Roche | Image: Mint
Previously-untreated patients with hepatocellular carcinoma (HCC), a common form of liver cancer, will have an immunotherapy-based treatment option after NICE gave the nod to NHS funding of Roche’s Tecentriq and Avastin combination therapy.
The decision by NICE comes shortly after Tecentriq (atezolizumab) and Avastin (bevacizumab) was approved by the European Commission as a first-line treatment for adults with advanced or inoperable HCC, becoming the first and only immunotherapy regimen approved in Europe for this patient group.
Approval was based on findings of the phase 3 IMbrave 150 study, which showed an improvement in overall survival compared with Bayer’s Nexavar (sorafenib), one of the standard treatments for previously-untreated liver cancer along with Eisai’s Lenvima (lenvatinib).
NICE’s final appraisal document notes that patients receiving the dual regimen “live longer and have longer before their disease progresses than people who have sorafenib” and it is a cost-effective use of NHS resources.
It is the first treatment to be approved in Europe for over a decade that has improved overall survival for people with previously untreated advanced or unresectable HCC.
HCC accounts for 90% of all liver cancer cases and there are around 5,900 new cases in the UK every year. The disease is also becoming more common – Roche says the incidence of HCC is projected to rise by 38% to 15 cases per 100,000 people by 2035.
“Tecentriq, in combination with Avastin, is the only cancer immunotherapy treatment, approved by NICE for this indication,” said Gemma Boni, head of liver cancer at Roche Products Ltd.
“We hope that it can help further improve overall survival rates, while having a generally manageable safety profile, compared to what is already achieved,” she added.
The Tecentriq/Avastin combination is crucial to Roche’s immuno-oncology franchise, and along with HCC has also been approved to treat non-squamous non-small cell lung cancer (NSCLC).
Sales of Tecentriq sales rose 64% to around $2.2 billion in the first nine months of this year, but Avastin has started to succumb to biosimilar competition, shrinking 22% to a little over $4 billion in the same period.
Cablivi gets green light for aTTP
NICE’s recommendation that Sanofi’s Cablivi (caplacizumab) can be covered by the NHS, is also a big step forward for patients with acquired thrombotic thrombocytopenic purpura (aTTP), a rare blood-clotting disorder that can be fatal without prompt treatment.
Cablivi is the first treatment specifically approved for aTTP in 30 years, and the only therapy approved for people experiencing an acute aTTP episode. NICE has backed the drug after rejecting it earlier this year due to an “improved commercial arrangement” with Sanofi – in other words a price discount.
Cablivi was also recommended for NHS use by the Scottish Medicines Consortium (SMC) in September.
aTTP is a rare disease where blood clots form in small blood vessels throughout the body, limiting the flow of oxygen to organs, such as the brain, kidney and heart. NICE’s appraisal document says that Cablivi, combined with plasma exchange and immunosuppression, reduces time to bring blood platelet levels back to normal.
Sanofi welcomed the positive recommendation, but said access to Cablivi had been delayed by procedural issues at NICE.
As a treatment for an ultra-rare disease, Cablivi was initially supposed to be considered within the Highly Specialised Technology (HST) process, but was assessed under the Single Technology Appraisal (STA) process.
The STA does not consider the concerns around long-term follow-up and management, which are a well-known issue in evaluating medicines for ultra-rare diseases, says the company, which claims this delayed access to the drug.
“We now hope that the forthcoming NICE Methods Review and Innovative Drugs Fund consultation will fix the ongoing barriers for patients,” commented Deborah Lough, head of rare blood disorders UK & Ireland at Sanofi Genzyme.
NICE estimates that more than 100 people each year will be eligible for treatment with Cablivi.
The approval is based on P-III IMbrave150 study involves assessing of Tecentriq (atezolizumab, 1200mg) + Avastin (bevacizumab, 15 mg/kg) on day 1 of each 21-day cycle vs sorafenib (400mg, bid) on days 1-21 of each 21-day cycle in 501 patients in a ratio (2:1) with unresectable HCC, prior not treated with systemic therapies
Result: reduction in the risk of OS (42%); reduction in the risk of disease worsening or death, PFS (41%); showed improvement in both OS and PFS; Grade 3–4 AEs (57% vs 55%), published in the NEJM
The approval follows an EMA’s CHMP positive opinion received in Sept’2020. The dual regimen also recently included as a class I, A recommendation by the ESMO for unresectable HCC, as well as by many clinical practice guidelines globally
Click here to read the full press release/ article | Ref: Roche | Image: National Foundation For Cancer Research
The approval was based on the P-III IMbrave150 study (n=501) assessing the combination of Tecentriq (1200 mg, IV) and Avastin (15 mg/kg, IV) or sorafenib (400 mg, bid) in unresectable HCC patients who had not received prior systemic therapy which included analyses of a cohort of Chinese patients (n=194) from the same study
Results: Tecentriq in combination with Avastin reduced the risk of OS by 56% (among Chinese patients) and 42% (global results) & the PFS risk by 40% (among Chinese patients) and 41% (global results) as compared with sorafenib
IMbrave150 is the 1st P-III cancer immunotherapy study to show an improvement in OS and PFS in people with unresectable or metastatic HCC compared with sorafenib. Additionally. in May 2020, the US FDA approved Tecentriq in combination with Avastin for the treatment of people with unresectable or metastatic HCC who have not received prior systemic therapy
Click here to read full press release/ article | Ref: Roche | Image: Business Recorder
The approval is based on P-III IMbrave150 study assessing Tecentriq (1200 mg) + bevacizumab (15 mg/kg, q3w, IV) vs sorafenib (400mg, bid) in 501 patients in a ratio (2:1) with unresectable or metastatic HCC, prior not treated with systemic therapies
Results: 42% reduction in risk of death (OS); 41% reduction the risk of disease worsening or death (PFS); @primary analysis, median survival follow up time (8.6mos.); 7.6mos. delay in median time to deterioration of patient-reported QoL
The approval is part of Project Orbis, an initiative of the FDA’s OCE which provides a framework for simultaneous submission and review of oncology products among international partners
Click here to read full press release/ article | Ref: Roche | Image: SOM
Roche’s hopes of extending the use of its PD-L1 inhibitor Tecentriq in triple-negative breast cancer (TNBC) have been dashed by a late-stage trial failure looking at the drug in combination with chemotherapy.
Adding Tecentriq to treatment with paclitaxel as a first-line treatment for TNBC patients whose tumours expressed the biomarker PD-L1 did not lengthen the time it took for the cancer to progress, when compared to paclitaxel plus placebo.
Moreover, there was a trend towards worse overall survival with Roche’s drug in the IMpassion131 study, although the company says the data on this are still immature and statistically underpowered.
TNBC is so called because it lacks the biomarkers that other targeted therapies can latch on to.It is more aggressive than other types of breast cancer, accounting for 15-20% of cases but causing 25% of deaths.
Tecentriq was the first drug among checkpoint inhibitors to get approval in TNBC, although rivals are circling, notably Merck & Co / MSD’s Keytruda (pembrolizumab).
“Today’s results underscore the need to better understand the cancer and immune system interactions, including the chemotherapy backbone and associated regimens,” said Roche’s chief medical officer Levi Garraway.
Roche’s drug is already licensed in more than 70 countries as a front-line treatment for PD-L1-positive forms of TNBC in a regimen with Bristol-Myers Squibb’s Abraxane (nab-paclitaxel) – a form of paclitaxel bound to the blood protein albumin to improve its delivery side effects – based on the IMpassion130 trial.
Tecentriq has had the frontline TNBC immunotherapy market to itself since it was approved last year, but is facing direct competition from Keytruda (pembrolizumab) in the wake of the KEYNOTE-355 trial reported in May.
That study showed Merck’s drug plus chemo reduced the risk of disease progression or death by 35% compared to chemo alone in PD-L1-positive TNBC, and will form the basis of regulatory filings later this year.
There’s little doubt that the arrival of Keytruda on the TNBC market would have an impact on Roche’s ambitions in this area, given the drug is the top-selling PD-1/PD-L1 inhibitor.
Failure in IMpassion131 puts a brake on growth in an indication that Roche has suggested could be worth $1 billion in sales on its own for Tecentriq, which brought in around $2 billion for Roche last year across its approved uses in TNBC, bladder and various forms of lung cancer.
It’s not all been bad news for Tecentriq of late, however. In June, Roche scored a major win for Tecentriq as a pre-surgery (neoadjuvant) therapy for TNBC patients – regardless of their PD-L1 status – on the back of the IMpassion031 trial, and is in the build-up to regulatory filings in this indication.
That would open up a much larger eligible patient population for the drug and extend its use into the 60% of TNBC patients with low PD-L1 expression levels. Merck is lurking in the wings in the neoadjuvant setting too though, thanks to the results of KEYNOTE-522 reported last year.
So far, none of the PD-1/PD-L1 inhibitors have been approved for neoadjuvant or adjuvant (post-surgery) use in any form of cancer.
The P-III IMpassion131 study involves assessing of Tecentriq + paclitaxel vs PBO + paclitaxel, in 651 people in a ratio (2:1) with previously untreated, inoperable, LA/ m-TNBC
The study did not meet its 1EPs of PFS for 1L treatment of people with m-TNBC) in the PD-L1+ population. The data for 2EPs of OS showed a negative trend, however, the study was not powered for the 2EPs of OS and data were immature at the time of analysis while OS follow-up is planned to continue until the final analysis
In the previous IMpassion130 study, Tecentriq + Abraxane demonstrated PFS benefit and, while not formally tested, showed improvements in OS for people with metastatic TNBC whose tumors express PD-L1
Click here to read full press release/ article | Ref: Roche | Image: Forbes
Roche’s checkpoint inhibitor Tecentriq has been cleared for another new use in the US – in melanoma – but could struggle to displace rival drugs from Bristol-Myers Squibb and Merck & Co.
The FDA has approved the PD-L1 inhibitor as a combination with two targeted drugs – MEK inhibitor Cotellic (cobimetinib) and BRAF inhibitor Zelboraf (vemurafenib) – as a first-line treatment for patients with advanced melanoma with BRAF V600 mutations.
The approval stems from the IMspire150 trial, which showed that the triplet therapy reduced the risk of disease progression or death compared to Cotellic, Zelboraf and placebo.
The median progression-free survival (PFS) was 15.1 months in the Tecentriq (atezolizumab) group compared with 10.6 months, although objective response rates in the two groups were similar at 66% and 65%, respectively.
That’s a solid result, and a compelling comparison to make when IMspire150 was started three years ago. Unfortunately for Roche, melanoma treatment has evolved in the interim and the standard of care for these patients has moved on.
BMS’ Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab) have been approved for use in melanoma since 2014, and right now the combination of Opdivo with BMS’ CTLA4-targeting checkpoint inhibitor Yervoy (ipilimumab) looks set to become the go-to therapy in the US.
Opdivo/Yervoy was cleared for BRAF V600-positive melanoma in 2015, and for all-comer melanoma patients the following year, giving oncologists years of experience with its use and – crucially – plenty of impressive follow-up data.
Last year, BMS reported updated results from the CheckMate-067 study showing that 52% of patients on the regimen were still alive five years later, with the benefit present even in patients who stopped taking the drugs early due to side effects.
Over the same period, Cotellic sales have shrunk from around $400 million to a little over $50m last year as immunotherapy displaced targeted therapy in this type of melanoma.
That said, there are tolerability issues with Opdivo/Yervoy that could encourage some doctors to consider the Tecentriq triple for their BRAF V600-positive patients. Overall however, melanoma is considered to be a nice addition to Tecentriq’s approved indications that won’t be a big driver for new sales.
That’s more likely to come from other new indications for Roche’s drug, including new approvals as a monotherapy and in combination with chemotherapy in previously-untreated non-small cell lung cancer (NSCLC) and as a combination with Roche’s Avastin (bevacizumab) in liver cancer.
The approval is based on P-III IMspire150 study assessing Tecentriq (atezolizumab) + Cotellic (cobimetinib) + Zelboraf (vemurafenib) vs PBO + Cotellic + Zelboraf in patients with BRAF V600 mutation-positive advanced melanoma
Results: mPFS (15.1 vs 10.6mos.); the safety profile of the Tecentriq combination was consistent with the known safety profiles of the individual medicines. The review was conducted under Project Orbis
Tecentriq is a mAb targeting PD-L1, acts by blocking is its interactions with both PD-1 and B7.1 receptor. Cotellic is a MEK1/2 inhibitor in a cell signaling pathway that helps control cell growth and survival while Zelboraf is a prescription medicine for melanoma that has spread to other parts of the body or cannot be removed by surgery and has a BRAF V600 mutation
Click here to read full press release/ article | Ref: Roche | Image: StraitTimes