Immunotherapy may make lung cancer to become a “chronic disease”

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Immunotherapy may make lung cancer to become a “chronic disease”

Immunotherapy may make lung cancer to become a “chronic disease”.  Immunotherapy allows lung cancer patients to live longer, and lung cancer can also be a “chronic disease”. 

The 5-year survival of cancer is an important indicator. After 5 years of cure, lung cancer patients may also become chronic diseases.

5-year survival is an important indicator of cancer treatment and a very important criterion for evaluating the efficacy of drugs.

In the era of chemotherapy, the prognosis of patients with advanced non-small cell lung cancer (NSCLC) is poor, and the 5-year survival rate of patients worldwide is at a low level.

In recent years, the emergence of tumor immunotherapy has completely changed the traditional treatment model that has been inherited for many years.

With the in-depth study of the relevant mechanisms of immune checkpoints and the development and application of inhibitors, the immunotherapy of lung cancer has entered a new era of rapid development.

As the most objective indicator for judging clinical prognosis, OS (overall survival) is the focus of most attention for patients and doctors.

The follow-up data of a number of immunological drugs show that immunotherapy can bring long survival to patients, and the chronic disease of lung cancer may not be far away from us.

▌The 5-year OS rate reached 31.9%, and nearly one-third of patients were still alive after five years

The PD-1 drug Pembrolizumab (Keytruda), as a “broad-spectrum anticancer drug”, is the first PD-1 monoclonal antibody approved by the FDA for the first-line treatment of non-small cell lung cancer. 

From March to November 2019, in only 8 months, Keytruda has successively obtained three first-line treatment indications for advanced non-small cell lung cancer (NSCLC), for patients with advanced non-small cell lung cancer with negative gene driver mutations. That is to say, regardless of squamous cell carcinoma or non-squamous cell carcinoma, regardless of PD-L1 expression, Keytruda combined chemotherapy can be selected in the first-line treatment; and patients with PD-L1 expression (TPS≥1%) can also choose Keytruda is a single-agent first-line treatment without combined chemotherapy.

At the European Medical Oncology (ESMO) conference in 2020, KEYNOTE-024 announced the five-year follow-up results of Keytruda for the first time. Compared with the platinum-containing chemotherapy regimen in the control group, the five-year OS rate of Keytruda single-agent first-line treatment is platinum-containing chemotherapy It is nearly twice as large as the group, which has pushed the survival benefit of patients with advanced lung cancer forward a big step.

KEYNOTE-024 is a study designed to evaluate the efficacy and safety of Keytruda as a single-agent first-line treatment of PD-L1 positive (TPS≥50%) and EGFR/ALK mutation-negative advanced non-small cell lung cancer (NSCLC), the control group As standard platinum-containing chemotherapy, the median follow-up time was 59.9 months (nearly 5 years).

The data is as of June 1, 2020, and the results show:

The median OS of the Keytruda single-agent and platinum-containing chemotherapy first-line treatment groups were 26.3 months and 13.4 months, respectively, and the 60-month OS rates were 31.9% and 16.3%, respectively. The 5-year OS rate of the Keytruda single-agent group was platinum-containing Nearly twice as much in the chemotherapy treatment group, and nearly one-third of the patients were still alive at five years.

The median PFS was 7.7 months and 5.5 months, respectively, and the 3-year PFS rates were 22.8% and 4.1%, respectively. The 3-year PFS rate of the Keytruda single-agent group was 5 times that of the chemotherapy group.

Nearly 66% of patients in the chemotherapy group received follow-up PD-1/PD-L1 inhibitor treatment (55% of them crossed over to the Keytruda group), and the risk of death was reduced by 38%;

At the same time, treatment-related adverse reactions in the pembrolizumab group were significantly lower than those in the chemotherapy group (76.6% vs. 90%), and no new adverse reactions were found after long-term follow-up.

It is worth noting that the objective response rate (ORR) of patients who completed 35 cycles (about 2 years) of Keytruda treatment was 82.1%, and the 3-year (about 5 years from randomization) OS rate of these patients was 81.4 %. These data indicate that patients receiving 2-year Keytruda monotherapy can obtain long-term survival (OS) benefits. This study has been published in the international journal “Journal of Clinical Oncology”.

Not only that, the early results of another single-arm phase 1b KEYNOTE-001 study showed that the 5-year OS rate of NSCLC patients with PD-L1 TPS score ≥50% who received Keytruda monotherapy was 29.6%. The application of immunotherapy has further improved the survival rate of patients with advanced lung cancer.

▌Immunotherapy for stage III lung cancer has the longest OS, and 43% of patients are still alive after 5 years

Different from early and advanced lung cancer, stage III lung cancer can be described as an “embarrassing cancer.” In the stage of stage III lung cancer, cancer cells have spread but are still confined in the chest cavity. Therefore, stage III lung cancer is also called locally advanced lung cancer. It is difficult to remove all cancer cells through surgery. Previously, the standard treatment for lung cancer in this stage was chemotherapy and radiotherapy (CRT), but the prognosis was not satisfactory and the long-term survival rate was very low.

The PACIFIC study is the use of immunity (duvalizumab) as a consolidation therapy for patients with inoperable locally advanced patients receiving standard platinum-containing regimens and concurrent radiotherapy and chemotherapy without disease progression. Based on the results of the research, the PACIFIC model has become a new standard for the treatment of such unresectable stage III NSCLC patients, and has been successively recommended by NCCN, CSCO and other clinical practice guidelines at home and abroad.

In December 2019, Duvalizumab (“I” drug) was approved for marketing in China for the treatment of unresectable, stage III non-small cell lung cancer that has not progressed after concurrent radiotherapy and chemotherapy. It has also become the first in mainland China. This PD-L1 monoclonal antibody brings hope of clinical cure for patients with stage III lung cancer.

At the ESMO meeting in 2020, Duvalvumab released the 4-year follow-up data for the PACIFIC study for the first time. The follow-up results showed that the 4-year OS rate in the duvalizumab group reached 49.6%. Simply put, half of the patients had survived 4 years after chemotherapy and radiotherapy, compared with 36.3 in the control group. %.

At the just-concluded 2021ASCO conference, the latest post-mortem analysis showed that after radiotherapy and chemotherapy, the 5-year overall survival rate of the duvalizumab treatment group was 42.9%, while that of the placebo group was 33.4%. The median overall survival (OS) of the duvalizumab group and the placebo group were 47.5 months and 29.1 months, respectively, which was 18.4 months longer than the placebo group. After treatment with a treatment course of up to one year, 33.1% of patients with stage III unresectable non-small cell lung cancer treated with duvalizumab did not have disease progression five years after enrollment, and comfort The dose group was 19%.

David Spigel, an investigator of the PACIFIC trial and chief scientific officer of the Sarah Cannon Institute, said: “This trial has once again created a new precedent for the treatment of unresectable stage III non-small cell lung cancer. Historically, only 15-30% of patients Survived for 5 years, but these results show that with Imfinzi treatment for one year, an estimated 43% of patients are still alive after 5 years, and three-quarters of them have no disease progression during this time. This is here A major achievement made at the 5-year milestone in the stage of the disease for the purpose of curing.”

▌Double immunity is coming, bringing long-term survival benefits to patients

While the immunization single drug is chasing, and the momentum is not diminished, the dual immunization treatment method has been on the stage.

As the world’s first PD-1 inhibitor nivolumab (abbreviated as O drug), it can be described as an old star drug, plus the classic drug of CTLA-4 monoclonal antibody ipilimumab (abbreviated as Y drug). Not yet listed in China), it is a strong alliance of 1+1>2. At present, there are two trials of Double Immunity in the field of non-small cell lung cancer that deserve attention, CheckMate -9LA and CheckMate -227.

Based on the Checkmate227 Phase III study, on May 15, 2020, the FDA approved O+Y for the first-line treatment of EGFR/ALK mutation-negative PD-L1 ≥ 1% advanced non-small cell lung cancer. At the 2020 ESMO conference, Double Immunity Research announced the research data of the Checkmate227 Asian subgroup.

As of February 28, 2020, the median follow-up time was 43.1 months. In terms of the 3-year OS rate:

Among the patients with PD-L1≥1%, the 3-year OS rate of the Asian population receiving dual immunotherapy reached 53%; among the patients with PD-L1≥1% and PD-L1<1%, the Asian population receiving dual immunotherapy The 3-year OS rate is 51%. Regardless of the expression status of PD-L1, in Asian populations, more than half of the patients survived for more than 3 years after receiving the dual-immune combination therapy, and the long-term survival benefit was obvious.

In the oral report of this year’s ASCO conference, another phase III clinical study on lung cancer, CheckMate -9LA, published two-year follow-up data, and the results were gratifying!

The results showed that compared with receiving four cycles of chemotherapy alone, nivolumab combined with ipilimumab and two cycles of chemotherapy can bring lasting survival benefits to patients with first-line advanced NSCLC. In this study, the 2-year survival rate of patients who received dual immunization combined with two cycles of chemotherapy reached 38%, while the 2-year survival rate of patients who received chemotherapy alone was 26%.

After extending the follow-up time, the median overall survival (mOS, the primary endpoint of this study) of patients receiving dual-immune chemotherapy reached 15.8 months, while the median OS of patients in the chemotherapy alone group was 11 months (HR: 0.72; 95 % CI: 0.61-0.86).

All key subgroups receiving nivolumab combined with ipilimumab and two-cycle chemotherapy have shown clinically significant efficacy, including patients with PD-L1<1% and ≥1%, squamous cell carcinoma or Patients with non-squamous cell carcinoma and patients with central nervous system metastasis.

Dr. Martin Reck, a CheckMate-9LA investigator, the German Center for Lung Research, and the Grosshansdorf Pulmonary Clinic, said: “After two years of follow-up, we have further seen the great potential of this therapy. Compared with chemotherapy alone, nivolumab Combining ipilimumab and chemotherapy can continue to improve the survival of patients.”

In the field of contemporary cancer treatment, tumor immunotherapy is undoubtedly a milestone. As a new type of treatment, immunotherapy is far less valuable to humans. From the multi-dimensional thinking of chemotherapy, low dose, and combination medication, immunotherapy will Bring more hope for cancer patients.

（source:internet, reference only)

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